It is all about proteases: From drug delivery to in vivo imaging and photomedicine

Current Medicinal Chemistry

Volumn 18, Issue 12, 2011, Pages 1785-1805

  Gabriel, D ^a,b,c   Zuluaga, M F ^a   Van Den Bergh, H ^d   Gurny, R ^a   Lange, N ^a,e  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

^b Massachusetts Institute of Technology Cambridge   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

^d EPFL   (Switzerland)

^e Quai Ernest Ansermet   (Switzerland)

Author keywords

Drug delivery; Peptide based prodrugs; Photodynamic therapy; Polymeric prodrugs; Protease sensitive chemotherapeutics; Protease sensitive fluorescence imaging agents; Protease sensitive photosensitizers; Proteases

Indexed keywords

4 MORPHOLINE CARBONYLHISTIDYLSERYLSERYLLYSYLLEUCYLGLUTAMINYLLEUCINE; ALANYLPHENYLALANYLLYSINE SPACER; ALENDRONIC ACID; ASPARTIC PROTEINASE; CARBOPLATIN; CHLORIN E6; CYSTEINE PROTEINASE; DOXORUBICIN; DRUG CARRIER; FLOXURIDINE; GLUTARYLHISTIDYLSERYLSERYLLYSYLLEUCYLGLUTAMINYLLEUCINE; GLYCYLLYSYLALANYLPHENYLALANYLARGINYLARGINYLLEUCINE; GLYCYLPHENYLALANYLLEUCYLGLYCINE; HISTIDYLSERYLSERYLLYSYLLEUCYLGLUTAMINE; METALLOPROTEINASE; METHOTREXATE; N (2 HYDROXYPROPYL) METHACRYLAMIDE; OPAXIO; PACLITAXEL; PACLITAXEL POLIGLUMEX; PHEOPHORBIDE A; PHOTOSENSITIZING AGENT; PRODRUG; PROLYLLEUCYLGLYCYLLEUCINE; PROTEINASE; PYROPHEOPHORBIDE A; SERINE PROTEINASE; SOBLIDOTIN; THAPSIGARGIN; THREONINE PROTEINASE; UNCLASSIFIED DRUG; VINBLASTINE;

ADVANCED CANCER; AMINO ACID SEQUENCE; ANTINEOPLASTIC ACTIVITY; ARTHRITIS; ARTICLE; BREAST CANCER; CANCER THERAPY; CARCINOGENESIS; CHRONIC INFLAMMATION; COLON TUMOR; COLORECTAL CANCER; CONGESTIVE HEART FAILURE; CYTOTOXICITY; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG RELEASE; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVITY; EXTRACELLULAR MATRIX; FEBRILE NEUTROPENIA; FLUORESCENCE IMAGING; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMAN; IN VIVO STUDY; LUNG CANCER; LUNG NON SMALL CELL CANCER; MUCOSA INFLAMMATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHOTODYNAMIC THERAPY; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN FUNCTION; SOLID TUMOR; UPREGULATION;

DIAGNOSTIC IMAGING; DRUG DELIVERY SYSTEMS; HUMANS; NEOPLASMS; PEPTIDE HYDROLASES; PHOTOSENSITIZING AGENTS; UP-REGULATION;

EID: 79955683222     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986711795496782     Document Type: Article

References (226)

1. Lopez-Otin, C.; Bond, J. S. Proteases: Multifunctional enzymes in life and disease. J. Biol. Chem., 2008, 283(45), 30433-30437.
2. Seife, C. Blunting nature's Swiss army knife. Science, 1997, 277, 1602-1603. (Pubitemid 27446203)
3. van Kempen, L. C.; de Visser, K. E.; Coussens, L. M. Inflammation, proteases and cancer. Eur. J. Cancer, 2006, 42, 728-734.
4. Garcia-Touchard, A.; Henry, T. D.; Sangiorgi, G.; Spagnoli, L. G.; Mauriello, A.; Conover, C.; Schwartz, R. S. Extracellular proteases in atherosclerosis and restenosis. Arterioscler. Thromb. Vasc. Biol., 2005, 25, 1119-1127. (Pubitemid 40776597)
5. Lutgens, S. P.; Cleutjens, K. B.; Daemen, M. J.; Heeneman, S. Cathepsin cysteine proteases in cardiovascular disease. FASEB J., 2007, 21, 3029-3041. (Pubitemid 47565524)
6. Wu, Q.; Kuo, H. C.; Deng, G. G. Serine proteases and cardiac function. Biochim. Biophys. Acta, 2005, 1751, 82-94. (Pubitemid 41033298)
7. Turner, A. J.; Nalivaeva, N. N. New insights into the roles of metalloproteinases in neurodegeneration and neuroprotection. Int. Rev. Neurobiol., 2007, 82, 113-135.
8. Haque, A.; Banik, N. L.; Ray, S. K. New insights into the roles of endolysosomal cathepsins in the pathogenesis of Alzheimer's disease: cathepsin inhibitors as potential therapeutics. CNS Neurol. Disord. Drug Targets, 2008, 7, 270-277.
9. Supuran, C. T.; Scozzafava, A.; Mastrolorenzo, A. Bacterial proteases: current therapeutic use and future prospects for the development of new antibiotics. Expert Opin. Therap. Patents, 2001, 11, 221-259. (Pubitemid 32117923)
10. Tong, L. Viral proteases. Chem. Rev., 2002, 102, 4609-4626.
11. McKerrow, J. H.; Caffrey, C.; Kelly, B.; Loke, P.; Sajid, M. Proteases in parasitic diseases. Annu. Rev. Pathol., 2006, 1, 497-536.
12. Turk, B. Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov., 2006, 5, 785-799. (Pubitemid 44323703)
13. Fear, G.; Komarnytsky, S.; Raskin, I. Protease inhibitors and their peptidomimetic derivatives as potential drugs. Pharmacol. Ther., 2007, 113, 354-368. (Pubitemid 46149049)
14. Docherty, A. J.; Crabbe, T.; O'Connell, J. P.; Groom, C. R. Proteases as drug targets. Biochem. Soc Symp., 2003, 147-161. (Pubitemid 38497223)
15. Denny, W. A. Prodrug strategies in cancer therapy. Eur. J. Med. Chem, 2001, 36, 577-595.
16. Denny, W. A. Tumor-activated prodrugs--a new approach to cancer therapy. Cancer Invest., 2004, 22, 604-619. (Pubitemid 39506881)
17. Atkinson, J. M.; Siller, C. S.; Gill, J. H. Tumor endoproteases: the cutting edge of cancer drug delivery? Br. J. Pharmacol., 2008, 153, 1344-1352. (Pubitemid 351481504)
18. Vicent, M. J.; Duncan, R. Polymer conjugates: nanosized medicines for treating cancer. Trends Biotechnol., 2006, 24, 39-47. (Pubitemid 43017749)
19. Weissleder, R.; Pittet, M. J. Imaging in the era of molecular oncology. Nature, 2008, 452, 580-589. (Pubitemid 351483372)
20. Quesada, V.; Ordonez, G. R.; Sanchez, L. M.; Puente, X. S.; Lopez-Otin, C. The Degradome database: mammalian proteases and diseases of proteolysis. Nucleic Acids Res., 2008, 37, D239-D243.
21. Carmel, A.; Zur, M.; Yaron, A.; Katchalski, E. Use of substrates with fluorescent donor and acceptor chromophores for the kinetic assay of hydrolases. FEBS Lett., 1973, 30, 11-14.
22. Latt, S. A.; Auld, D. S.; Vallee, B. L. Fluorescende determination of carboxypeptidase A activity based on electronic energy transfer. Anal. Biochem., 1972, 50, 56-62.
23. Neefjes, J.; Dantuma, N. P. Fluorescent probes for proteolysis: tools for drug discovery. Nat. Rev. Drug Discov., 2004, 3, 58-69. (Pubitemid 38088698)
24. Mahmood, U.; Weissleder, R. Near-infrared optical imaging of proteases in cancer. Mol. Cancer Ther., 2003, 2, 489-496.
25. McIntyre, J. O.; Matrisian, L. M. Molecular imaging of proteolytic activity in cancer. J. Cell Biochem., 2003, 90, 1087-1097. (Pubitemid 37485047)
26. Sloane, B. F.; Sameni, M.; Podgorski, I.; Cavallo-Medved, D.; Moin, K. Functional imaging of tumor proteolysis. Annu. Rev. Pharmacol. Toxicol., 2006, 46, 301-315. (Pubitemid 43271192)
27. Hopper, C. Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol., 2000, 1, 212-219.
28. Dolmans, D. E.; Fukumura, D.; Jain, R. K. Photodynamic therapy for cancer. Nat. Rev. Cancer, 2003, 3, 380-387. (Pubitemid 37328858)
29. Puente, X. S.; Sanchez, L. M.; Gutierrez-Fernandez, A.; Velasco, G.; Lopez- Otin, C. A genomic view of the complexity of mammalian proteolytic systems. Biochem. Soc Trans., 2005, 33, 331-334. (Pubitemid 40604365)
30. Rawlings, N. D.; Morton, F. R.; Kok, C. Y.; Kong, J.; Barrett, A. J. MEROPS: the peptidase database. Nucleic Acids Res., 2008, 36, D320-D325. (Pubitemid 351149743)
31. Hubbard, S. J. The structural aspects of limited proteolysis of native proteins. Biochim. Biophys. Acta, 1998, 1382, 191-206. (Pubitemid 28130392)
32. Basbaum, C. B.; Werb, Z. Focalized proteolysis: spatial and temporal regulation of extracellular matrix degradation at the cell surface. Curr. Opin. Cell Biol., 1996, 8, 731-738. (Pubitemid 26381732)
33. Hollenberg, M. D. Protease-mediated signalling: new paradigms for cell regulation and drug development. Trends Pharmacol. Sci., 1996, 17, 3-6. (Pubitemid 26027735)
34. Ramachandran, R.; Hollenberg, M. D. Proteinases and signalling: pathophysiological and therapeutic implications via PARs and more. Br. J. Pharmacol., 2008, 153 Suppl 1, S263-S282. (Pubitemid 351340983)
35. Brix, K.; Dunkhorst, A.; Mayer, K.; Jordans, S. Cysteine cathepsins: cellular roadmap to different functions. Biochimie, 2008, 90, 194-207. (Pubitemid 351172569)
36. Mohamed, M. M.; Sloane, B. F. Cysteine cathepsins: multifunctional enzymes in cancer. Nat. Rev Cancer, 2006, 6, 764-775. (Pubitemid 44450465)
37. Turk, B.; Stoka, V. Protease signalling in cell death: caspases versus cysteine cathepsins. FEBS Lett., 2007, 581, 2761-2767. (Pubitemid 46874395)
38. Berdowska, I. Cysteine proteases as disease markers. Clin. Chim. Acta, 2004, 342, 41-69. (Pubitemid 38352913)
39. Roshy, S.; Sloane, B. F.; Moin, K. Pericellular cathepsin B and malignant progression. Cancer Metastasis Rev, 2003, 22, 271-286. (Pubitemid 36561062)
40. Gocheva, V.; Joyce, J. A. Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle, 2007, 6, 60-64. (Pubitemid 46173882)
41. Koblinski, J. E.; Ahram, M.; Sloane, B. F. Unraveling the role of proteases in cancer. Clin. Chim. Acta, 2000, 291, 113-135. (Pubitemid 30089760)
42. Kos, J.; Werle, B.; Lah, T.; Brunner, N. Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. Int. J. Biol. Markers, 2000, 15, 84-89. (Pubitemid 30195490)
43. Yano, M.; Hirai, K.; Naito, Z.; Yokoyama, M.; Ishiwata, T.; Shiraki, Y.; Inokuchi, M.; Asano, G. Expression of cathepsin B and cystatin C in human breast cancer. Surg. Today, 2001, 31, 385-389. (Pubitemid 32441901)
44. Lah, T. T.; Kokalj-Kunovar, M.; Drobnic-Kosorok, M.; Babnik, J.; Golouh, R.; Vrhovec, I.; Turk, V. Cystatins and cathepsins in breast carcinoma. Biol. Chem Hoppe Seyler, 1992, 373, 595-604.
45. Lah, T. T.; Calaf, G.; Kalman, E.; Shinde, B. G.; Russo, J.; Jarosz, D.; Zabrecky, J.; Somers, R.; Daskal, I. Cathepsins D, B and L in breast carcinoma and in transformed human breast epithelial cells (HBEC). Biol. Chem Hoppe Seyler, 1995, 376, 357-363.
46. Staack, A.; Tolic, D.; Kristiansen, G.; Schnorr, D.; Loening, S. A.; Jung, K. Expression of cathepsins B, H, and L and their inhibitors as markers of transitional cell carcinoma of the bladder. Urology, 2004, 63, 1089-1094. (Pubitemid 38746809)
47. Hazen, L. G.; Bleeker, F. E.; Lauritzen, B.; Bahns, S.; Song, J.; Jonker, A.; Van Driel, B. E.; Lyon, H.; Hansen, U.; Kohler, A.; Van Noorden, C. J. Comparative localization of cathepsin B protein and activity in colorectal cancer. J. Histochem. Cytochem., 2000, 48, 1421-1430.
48. Adenis, A.; Huet, G.; Zerimech, F.; Hecquet, B.; Balduyck, M.; Peyrat, J. P. Cathepsin B, L, and D activities in colorectal carcinomas: relationship with clinico-pathological parameters. Cancer Lett., 1995, 96, 267-275.
49. Shuja, S.; Sheahan, K.; Murnane, M. J. Cysteine endopeptidase activity levels in normal human tissues, colorectal adenomas and carcinomas. Int. J. Cancer, 1991, 49, 341-346.
50. Hughes, S. J.; Glover, T. W.; Zhu, X. X.; Kuick, R.; Thoraval, D.; Orringer, M. B.; Beer, D. G.; Hanash, S. A novel amplicon at 8p22-23 results in overexpression of cathepsin B in esophageal adenocarcinoma. Proc. Natl. Acad. Sci. U. S. A, 1998, 95, 12410-12415. (Pubitemid 28483779)
51. Linnerth, N. M.; Sirbovan, K.; Moorehead, R. A. Use of a transgenic mouse model to identify markers of human lung tumors. Int. J. Cancer, 2005, 114, 977-982.
52. Page, M. J.; Di Cera, E. Serine peptidases: classification, structure and function. Cell Mol. Life Sci., 2008, 65, 1220-1236.
53. Barth, A.; Frost, K.; Wahab, M.; Brandt, W.; Schadler, H. D.; Franke, R. Classification of serine proteases derived from steric comparisons of their active sites, part II: "Ser, His, Asp arrangements in proteolytic and nonproteolytic proteins". Drug Des. Discov., 1994, 12, 89-111. (Pubitemid 24365628)
54. Dass, K.; Ahmad, A.; Azmi, A. S.; Sarkar, S. H.; Sarkar, F. H. Evolving role of uPA/uPAR system in human cancers. Cancer Treat. Rev., 2008, 34, 122-136.
55. Syrovets, T.; Simmet, T. Novel aspects and new roles for the serine protease plasmin. Cell Mol. Life Sci., 2004, 61, 873-885. (Pubitemid 38651004)
56. Sidenius, N.; Blasi, F. The urokinase plasminogen activator system in cancer: recent advances and implication for prognosis and therapy. Cancer Metastasis Rev., 2003, 22, 205-222. (Pubitemid 36561058)
57. Andreasen, P. A.; Kjoller, L.; Christensen, L.; Duffy, M. J. The urokinasetype plasminogen activator system in cancer metastasis: a review. Int. J. Cancer, 1997, 72, 1-22. (Pubitemid 27314632)
58. Kim, T. D.; Song, K. S.; Li, G.; Choi, H.; Park, H. D.; Lim, K.; Hwang, B. D.; Yoon, W. H. Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer. BMC Cancer, 2006, 6, 211
59. Herszenyi, L.; Plebani, M.; Carraro, P.; De Paoli, M.; Roveroni, G.; Cardin, R.; Foschia, F.; Tulassay, Z.; Naccarato, R.; Farinati, F. Proteases in gastrointestinal neoplastic diseases. Clin. Chim. Acta, 2000, 291, 171-187. (Pubitemid 30089763)
60. Cozzi, P. J.; Wang, J.; Delprado, W.; Madigan, M. C.; Fairy, S.; Russell, P. J.; Li, Y. Evaluation of urokinase plasminogen activator and its receptor in different grades of human prostate cancer. Hum. Pathol., 2006, 37, 1442-1451. (Pubitemid 44584322)
61. Daneri-Navarro, A.; Macias-Lopez, G.; Oceguera-Villanueva, A.; Toro- Arreola, S.; Bravo-Cuellar, A.; Perez-Montfort, R.; Orbach-Arbouys, S. Urokinase-type plasminogen activator and plasminogen activator inhibitors (PAI-1 and PAI-2) in extracts of invasive cervical carcinoma and precursor lesions. Eur. J. Cancer, 1998, 34, 566-569. (Pubitemid 28179356)
62. Denmeade, S. R.; Sokoll, L. J.; Chan, D. W.; Khan, S. R.; Isaacs, J. T. Concentration of enzymatically active prostate-specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models. Prostate, 2001, 48, 1-6. (Pubitemid 32545071)
63. Rittenhouse, H. G.; Finlay, J. A.; Mikolajczyk, S. D.; Partin, A. W. Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Crit. Rev. Clin. Lab. Sci., 1998, 35, 275-368. (Pubitemid 28458755)
64. Shariat, S. F.; Karam, J. A.; Margulis, V.; Karakiewicz, P. I. New bloodbased biomarkers for the diagnosis, staging and prognosis of prostate cancer. BJU Int., 2008, 101, 675-683. (Pubitemid 351269995)
65. Reynolds, M. A.; Kastury, K.; Groskopf, J.; Schalken, J. A.; Rittenhouse, H. Molecular markers for prostate cancer. Cancer Lett., 2007, 249, 5-13. (Pubitemid 46428001)
66. Bode, W.; Gomis-Ruth, F. X.; Stockler, W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the 'metzincins'. FEBS Lett., 1993, 331, 134-140. (Pubitemid 23285641)
67. Murphy, G.; Nagase, H. Progress in matrix metalloproteinase research. Mol. Aspects Med., 2008, 29(5), 290-308.
68. Malemud, C. J. Matrix metalloproteinases (MMPs) in health and disease: an overview. Front Biosci., 2006, 11, 1696-1701. (Pubitemid 43253387)
69. Van Wart, H. E.; Birkedal-Hansen, H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc. Natl. Acad. Sci. U.S.A., 1990, 87, 5578-5582.
70. Liotta, L. A.; Tryggvason, K.; Garbisa, S.; Hart, I.; Foltz, C. M.; Shafie, S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature, 1980, 284, 67-68. (Pubitemid 10098769)
71. Duffy, M. J.; Lynn, D. J.; Lloyd, A. T.; O'Shea, C. M. The ADAMs family of proteins: from basic studies to potential clinical applications. Thromb. Haemost., 2003, 89, 622-631. (Pubitemid 36456959)
72. Seals, D. F.; Courtneidge, S. A. The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev., 2003, 17, 7-30. (Pubitemid 36062504)
73. McCawley, L. J.; Matrisian, L. M. Matrix metalloproteinases: they're not just for matrix anymore! Curr. Opin. Cell Biol., 2001, 13, 534-540. (Pubitemid 32817010)
74. Deryugina, E. I.; Quigley, J. P. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev, 2006, 25, 9-34. (Pubitemid 43723979)
75. Hoekstra, R.; Eskens, F. A.; Verweij, J. Matrix metalloproteinase inhibitors: current developments and future perspectives. Oncologist., 2001, 6, 415-427. (Pubitemid 33022212)
76. Brinckerhoff, C. E.; Rutter, J. L.; Benbow, U. Interstitial collagenases as markers of tumor progression. Clin. Cancer Res., 2000, 6, 4823-4830. (Pubitemid 32110426)
77. Pesta, M.; Holubec, L., Jr.; Topolcan, O.; Cerna, M.; Rupert, K.; Holubec, L. S.; Treska, V.; Kormunda, S.; Elgrova, L.; Finek, J.; Cerny, R. Quantitativeestimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples. Anticancer Res., 2005, 25, 3387-3391. (Pubitemid 41105215)
78. Schwandner, O.; Schlamp, A.; Broll, R.; Bruch, H. P. Clinicopathologic and prognostic significance of matrix metalloproteinases in rectal cancer. Int. J. Colorectal Dis., 2007, 22, 127-136. (Pubitemid 44964015)
79. Zucker, S.; Vacirca, J. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev, 2004, 23, 101-117. (Pubitemid 38221598)
80. Parsons, S. L.; Watson, S. A.; Collins, H. M.; Griffin, N. R.; Clarke, P. A.; Steele, R. J. Gelatinase (MMP-2 and -9) expression in gastrointestinal malignancy. Br. J. Cancer, 1998, 78, 1495-1502. (Pubitemid 28517547)
81. Visscher, D. W.; Hoyhtya, M.; Ottosen, S. K.; Liang, C. M.; Sarkar, F. H.; Crissman, J. D.; Fridman, R. Enhanced expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the stroma of breast carcinomas correlates with tumor recurrence. Int. J. Cancer, 1994, 59, 339-344. (Pubitemid 24331823)
82. Vizoso, F. J.; Gonzalez, L. O.; Corte, M. D.; Rodriguez, J. C.; Vazquez, J.; Lamelas, M. L.; Junquera, S.; Merino, A. M.; Garcia-Muniz, J. L. Study of matrix metalloproteinases and their inhibitors in breast cancer. Br. J. Cancer, 2007, 96, 903-911. (Pubitemid 46452295)
83. Davies, B.; Waxman, J.; Wasan, H.; Abel, P.; Williams, G.; Krausz, T.; Neal, D.; Thomas, D.; Hanby, A.; Balkwill, F. Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion. Cancer Res., 1993, 53, 5365-5369. (Pubitemid 23342150)
84. Zhang, X.; Zhu, S.; Luo, G.; Zheng, L.; Wei, J.; Zhu, J.; Mu, Q.; Xu, N. Expression of MMP-10 in lung cancer. Anticancer Res., 2007, 27, 2791-2795. (Pubitemid 47227999)
85. Liu, D.; Nakano, J.; Ishikawa, S.; Yokomise, H.; Ueno, M.; Kadota, K.; Urushihara, M.; Huang, C. L. Overexpression of matrix metalloproteinase-7 (MMP-7) correlates with tumor proliferation, and a poor prognosis in nonsmall cell lung cancer. Lung Cancer, 2007, 58, 384-391. (Pubitemid 350051513)
86. Hooper, N. M. Proteases: a primer. Essays Biochem., 2002, 38, 1-8. (Pubitemid 36589190)
87. Dunn, B. M. Overview of pepsin-like aspartic peptidases. Curr. Protoc. Protein Sci., 2001, Chapter 21, Unit 21.3.
88. Guagliardi, L. E.; Koppelman, B.; Blum, J. S.; Marks, M. S.; Cresswell, P.; Brodsky, F. M. Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment. Nature, 1990, 343, 133-139.
89. Vassar, R. BACE1: the beta-secretase enzyme in Alzheimer's disease. J. Mol. Neurosci., 2004, 23, 105-114.
90. Cole, S.L.; Vassar, R. BACE1 structure and function in health and Alzheimer's disease. Curr Alzheimer Res., 2008, 5(2), 100-20. (Pubitemid 351536336)
91. Szecsi, P. B. The aspartic proteases. Scand. J. Clin. Lab Invest Suppl, 1992, 210, 5-22.
92. Aziz, S.; Pervez, S.; Khan, S.; Kayani, N.; Rahbar, M. Immunohistochemical cathepsin-D expression in breast cancer: correlation with established pathological parameters and survival. Pathol. Res. Pract., 2001, 197, 551-557.
93. Riley, L. B.; Lange, M. K.; Browne, R. J.; Cochrane, P. J.; Choi, I. J.; Davis, B.; Arcona, S.; Alhadeff, J. A. Analysis of cathepsin D in human breast cancer: usefulness of the processed 31 kDa active form of the enzyme as a prognostic indicator in node-negative and node-positive patients. Breast Cancer Res. Treat., 2000, 60, 173-179. (Pubitemid 30307477)
94. Tandon, A. K.; Clark, G. M.; Chamness, G. C.; Chirgwin, J. M.; McGuire, W. L. Cathepsin D and prognosis in breast cancer. N. Engl. J. Med., 1990, 322, 297-302. (Pubitemid 20046332)
95. Cherry, J. P.; Mordente, J. A.; Chapman, J. R.; Choudhury, M. S.; Tazaki, H.; Mallouh, C.; Konno, S. Analysis of cathepsin D forms and their clinical implications in human prostate cancer. J. Urol., 1998, 160, 2223-2228. (Pubitemid 128703659)
96. Makar, R.; Mason, A.; Kittelson, J. M.; Bowden, G. T.; Cress, A. E.; Nagle, R. B. Immunohistochemical analysis of cathepsin D in prostate carcinoma. Mod. Pathol., 1994, 7, 747-751.
97. Lipponen, P. K. Expression of cathepsin D in transitional cell bladder tumours. J. Pathol., 1996, 178, 59-64. (Pubitemid 26053396)
98. Carl, P. L.; Chakravarty, P. K.; Katzenellenbogen, J. A.; Weber, M. J. Protease-activated "prodrugs" for cancer chemotherapy. Proc. Natl. Acad. Sci. U. S. A, 1980, 77, 2224-2228.
99. Devy, L.; de Groot, F. M.; Blacher, S.; Hajitou, A.; Beusker, P. H.; Scheeren, H. W.; Foidart, J. M.; Noel, A. Plasmin-activated doxorubicin prodrugs containing a spacer reduce tumor growth and angiogenesis without systemic toxicity. FASEB J., 2004, 18, 565-567.
100. Denmeade, S. R.; Nagy, A.; Gao, J.; Lilja, H.; Schally, A. V.; Isaacs, J. T. Enzymatic activation of a doxorubicin-peptide prodrug by prostate-specific antigen. Cancer Res., 1998, 58, 2537-2540. (Pubitemid 28275422)
101. DeFeo-Jones, D.; Garsky, V. M.; Wong, B. K.; Feng, D. M.; Bolyar, T.; Haskell, K.; Kiefer, D. M.; Leander, K.; McAvoy, E.; Lumma, P.; Wai, J.; Senderak, E. T.; Motzel, S. L.; Keenan, K.; Van Zwieten, M.; Lin, J. H.; Freidinger, R.; Huff, J.; Oliff, A.; Jones, R. E. A peptide-doxorubicin 'prodrug' activated by prostate-specific antigen selectively kills prostate tumor cells positive for prostate-specific antigen in vivo. Nat. Med., 2000, 6, 1248-1252.
102. DeFeo-Jones, D.; Brady, S. F.; Feng, D. M.; Wong, B. K.; Bolyar, T.; Haskell, K.; Kiefer, D. M.; Leander, K.; McAvoy, E.; Lumma, P.; Pawluczyk, J. M.; Wai, J.; Motzel, S. L.; Keenan, K.; Van Zwieten, M.; Lin, J. H.; Garsky, V. M.; Freidinger, R.; Oliff, A.; Jones, R. E. A prostatespecific antigen (PSA)-activated vinblastine prodrug selectively kills PSAsecreting cells in vivo. Mol. Cancer Ther., 2002, 1, 451-459.
103. Brady, S. F.; Pawluczyk, J. M.; Lumma, P. K.; Feng, D. M.; Wai, J. M.; Jones, R.; DeFeo-Jones, D.; Wong, B. K.; Miller-Stein, C.; Lin, J. H.; Oliff, A.; Freidinger, R. M.; Garsky, V. M. Design and synthesis of a pro-drug of vinblastine targeted at treatment of prostate cancer with enhanced efficacy and reduced systemic toxicity. J. Med. Chem, 2002, 45, 4706-4715.
104. Khan, S. R.; Denmeade, S. R. In vivo activity of a PSA-activated doxorubicin prodrug against PSA-producing human prostate cancer xenografts. Prostate, 2000, 45, 80-83.
105. DiPaola, R. S.; Rinehart, J.; Nemunaitis, J.; Ebbinghaus, S.; Rubin, E.; Capanna, T.; Ciardella, M.; Doyle-Lindrud, S.; Goodwin, S.; Fontaine, M.; Adams, N.; Williams, A.; Schwartz, M.; Winchell, G.; Wickersham, K.; Deutsch, P.; Yao, S. L. Characterization of a novel prostate-specific antigenactivated peptide-doxorubicin conjugate in patients with prostate cancer. J. Clin. Oncol., 2002, 20, 1874-1879. (Pubitemid 34273279)
106. Wong, B. K.; DeFeo-Jones, D.; Jones, R. E.; Garsky, V. M.; Feng, D. M.; Oliff, A.; Chiba, M.; Ellis, J. D.; Lin, J. H. PSA-specific and non-PSAspecific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites. Drug Metab Dispos., 2001, 29, 313-318. (Pubitemid 32179533)
107. Mhaka, A.; Denmeade, S. R.; Yao, W.; Isaacs, J. T.; Khan, S. R. A 5- fluorodeoxyuridine prodrug as targeted therapy for prostate cancer. Bioorg. Med. Chem Lett., 2002, 12, 2459-2461. (Pubitemid 34879890)
108. Denmeade, S. R.; Jakobsen, C. M.; Janssen, S.; Khan, S. R.; Garrett, E. S.; Lilja, H.; Christensen, S. B.; Isaacs, J. T. Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. J. Natl. Cancer Inst., 2003, 95, 990-1000. (Pubitemid 36896716)
109. Kumar, S. K.; Williams, S. A.; Isaacs, J. T.; Denmeade, S. R.; Khan, S. R. Modulating paclitaxel bioavailability for targeting prostate cancer. Bioorg. Med. Chem, 2007, 15, 4973-4984. (Pubitemid 46836826)
110. Janssen, S.; Rosen, D. M.; Ricklis, R. M.; Dionne, C. A.; Lilja, H.; Christensen, S. B.; Isaacs, J. T.; Denmeade, S. R. Pharmacokinetics, biodistribution, and antitumor efficacy of a human glandular kallikrein 2 (hK2)-activated thapsigargin prodrug. Prostate, 2006, 66, 358-368. (Pubitemid 43346946)
111. Janssen, S.; Jakobsen, C. M.; Rosen, D. M.; Ricklis, R. M.; Reineke, U.; Christensen, S. B.; Lilja, H.; Denmeade, S. R. Screening a combinatorial peptide library to develop a human glandular kallikrein 2-activated prodrug as targeted therapy for prostate cancer. Mol. Cancer Ther., 2004, 3, 1439-1450. (Pubitemid 39562589)
112. Kline, T.; Torgov, M. Y.; Mendelsohn, B. A.; Cerveny, C. G.; Senter, P. D. Novel antitumor prodrugs designed for activation by matrix metalloproteinases-2 and -9. Mol. Pharm., 2004, 1, 9-22.
113. Albright, C. F.; Graciani, N.; Han, W.; Yue, E.; Stein, R.; Lai, Z.; Diamond, M.; Dowling, R.; Grimminger, L.; Zhang, S. Y.; Behrens, D.; Musselman, A.; Bruckner, R.; Zhang, M.; Jiang, X.; Hu, D.; Higley, A.; Dimeo, S.; Rafalski, M.; Mandlekar, S.; Car, B.; Yeleswaram, S.; Stern, A.; Copeland, R. A.; Combs, A.; Seitz, S. P.; Trainor, G. L.; Taub, R.; Huang, P.; Oliff, A. Matrix metalloproteinase-activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicity. Mol. Cancer Ther., 2005, 4, 751-760. (Pubitemid 40767119)
114. Denmeade, S. R.; Nagy, A.; Gao, J.; Lilja, H.; Schally, A. V.; Isaacs, J. T. Enzymatic activation of a doxorubicin-peptide prodrug by prostate-specific antigen. Cancer Res., 1998, 58, 2537-2540. (Pubitemid 28275422)
115. Ringsdorf, H. Structure and properties of pharmacologically active polymers. J. Polymer Sci. Polymer Symposia, 2004, 51, 135-153.
116. Maeda, H.; Wu, J.; Sawa, T.; Matsumura, Y.; Hori, K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control Rel., 2000, 65, 271-284. (Pubitemid 30122932)
117. Duncan, R. Polymer conjugates as anticancer nanomedicines. Nat. Rev Cancer, 2006, 6, 688-701. (Pubitemid 44286001)
118. Greco, F.; Vicent, M. J. Polymer-drug conjugates: current status and future trends. Front Biosci., 2008, 13, 2744-2756. (Pubitemid 351611606)
119. Li, C.; Yu, D. F.; Newman, R. A.; Cabral, F.; Stephens, L. C.; Hunter, N.; Milas, L.; Wallace, S. Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate. Cancer Res., 1998, 58, 2404-2409. (Pubitemid 28252701)
120. Shaffer, S. A.; Baker-Lee, C.; Kennedy, J.; Lai, M. S.; de Vries, P.; Buhler, K.; Singer, J. W. In vitro and in vivo metabolism of paclitaxel poliglumex: identification of metabolites and active proteases. Cancer Chemother. Pharmacol., 2007, 59, 537-548. (Pubitemid 46122332)
121. Chipman, S. D.; Oldham, F. B.; Pezzoni, G.; Singer, J. W. Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int. J. Nanomed., 2006, 1, 375-383.
122. O'Brien, M. E.; Socinski, M. A.; Popovich, A. Y.; Bondarenko, I. N.; Tomova, A.; Bilynsky, B. T.; Hotko, Y. S.; Ganul, V. L.; Kostinsky, I. Y.; Eisenfeld, A. J.; Sandalic, L.; Oldham, F. B.; Bandstra, B.; Sandler, A. B.; Singer, J. W. Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naive advanced nonsmall cell lung cancer. J. Thorac. Oncol., 2008, 3, 728-734.
123. Paz-Ares, L.; Ross, H.; O'Brien, M.; Riviere, A.; Gatzemeier, U.; Von Pawel, J.; Kaukel, E.; Freitag, L.; Digel, W.; Bischoff, H.; Garcia-Campelo, R.; Iannotti, N.; Reiterer, P.; Bover, I.; Prendiville, J.; Eisenfeld, A. J.; Oldham, F. B.; Bandstra, B.; Singer, J. W.; Bonomi, P. Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-smallcell lung cancer. Br. J. Cancer, 2008, 98, 1608-1613. (Pubitemid 351684693)
124. Hoes, C.; Potman, W.; Heeswijk, V. Optimization of macromolecularprodrugs of the antitumor metabolite antibiotic adriamycin. J. Control. Rel., 1985, 2, 205-213. (Pubitemid 16195940)
125. Vasey, P. A.; Kaye, S. B.; Morrison, R.; Twelves, C.; Wilson, P.; Duncan, R.; Thomson, A. H.; Murray, L. S.; Hilditch, T. E.; Murray, T.; Burtles, S.; Fraier, D.; Frigerio, E.; Cassidy, J. Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents-drug-polymer conjugates. Cancer Research Campaign Phase I/II Committee. Clin. Cancer Res., 1999, 5, 83-94. (Pubitemid 29045181)
126. Seymour, L. W.; Ferry, D. R.; Anderson, D.; Hesslewood, S.; Julyan, P. J.; Poyner, R.; Doran, J.; Young, A. M.; Burtles, S.; Kerr, D. J. Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. J. Clin. Oncol., 2002, 20, 1668-1676. (Pubitemid 34260549)
127. Malugin, A.; Kopeckova, P.; Kopecek, J. Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells. J. Control Rel., 2007, 124, 6-10. (Pubitemid 350088209)
128. Loadman, P. M.; Bibby, M. C.; Double, J. A.; Al Shakhaa, W. M.; Duncan, R. Pharmacokinetics of PK1 and doxorubicin in experimental colon tumor models with differing responses to PK1. Clin. Cancer Res., 1999, 5, 3682-3688.
129. Duncan, R.; Coatsworth, J. K.; Burtles, S. Preclinical toxicology of a novel polymeric antitumour agent: HPMA copolymer-doxorubicin (PK1). Hum. Exp. Toxicol., 1998, 17, 93-104. (Pubitemid 28076000)
130. Yeung, T. K.; Hopewell, J. W.; Simmonds, R. H.; Seymour, L. W.; Duncan, R.; Bellini, O.; Grandi, M.; Spreafico, F.; Strohalm, J.; Ulbrich, K. Reduced cardiotoxicity of doxorubicin given in the form of N-(2- hydroxypropyl) methacrylamide conjugates: and experimental study in the rat. Cancer Chemother. Pharmacol., 1991, 29, 105-111.
131. Seymour, L. W.; Ulbrich, K.; Strohalm, J.; Kopecek, J.; Duncan, R. The pharmacokinetics of polymer-bound adriamycin. Biochem. Pharmacol., 1990, 39, 1125-1131. (Pubitemid 20103687)
132. Minko, T.; Kopeckova, P.; Pozharov, V.; Kopecek, J. HPMA copolymer bound adriamycin overcomes MDR1 gene encoded resistance in a human ovarian carcinoma cell line. J. Control Rel., 1998, 54, 223-233. (Pubitemid 28342701)
133. Minko, T.; Kopeckova, P.; Kopecek, J. Comparison of the anticancer effect of free and HPMA copolymer-bound adriamycin in human ovarian carcinoma cells. Pharm. Res., 1999, 16, 986-996. (Pubitemid 29368143)
134. Duncan, R.; Kopeckova, P.; Strohalm, J.; Hume, I. C.; Lloyd, J. B.; Kopecek, J. Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers. II. Evaluation of daunomycin conjugates in vivo against L1210 leukaemia. Br. J. Cancer, 1988, 57, 147-156.
135. Putnam, D.; Kopecek, J. Enantioselective release of 5-fluorouracil from N- (2-hydroxypropyl)methacrylamide-based copolymers via lysosomal enzymes. Bioconjug. Chem, 1995, 6, 483-492.
136. Gianasi, E.; Buckley, R. G.; Latigo, J.; Wasil, M.; Duncan, R. HPMA copolymers platinates containing dicarboxylato ligands. Preparation, characterisation and in vitro and in vivo evaluation. J. Drug Target, 2002, 10, 549-556. (Pubitemid 36124353)
137. Meerum Terwogt, J. M.; Bokkel Huinink, W. W.; Schellens, J. H.; Schot, M.; Mandjes, I. A.; Zurlo, M. G.; Rocchetti, M.; Rosing, H.; Koopman, F. J.; Beijnen, J. H. Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxel. Anticancer Drugs, 2001, 12, 315-323. (Pubitemid 32453436)
138. Pan, H.; Kopeckova, P.; Wang, D.; Yang, J.; Miller, S.; Kopecek, J. Watersoluble HPMA copolymer--prostaglandin E1 conjugates containing a cathepsin K sensitive spacer. J Drug Target, 2006, 14, 425-435. (Pubitemid 44203521)
139. Pan, H.; Liu, J.; Dong, Y.; Sima, M.; Kopeckova, P.; Brandi, M. L.; Kopecek, J. Release of prostaglandin E(1) from N-(2-hydroxypropyl) methacrylamide copolymer conjugates by bone cells. Macromol. Biosci., 2008, 8, 599-605.
140. Pan, H.; Sima, M.; Kopeckova, P.; Wu, K.; Gao, S.; Liu, J.; Wang, D.; Miller, S. C.; Kopecek, J. Biodistribution and pharmacokinetic studies of bone-targeting N-(2-hydroxypropyl)methacrylamide copolymer-alendronate conjugates. Mol. Pharm., 2008, 5, 548-558.
141. Chandran, S. S.; Nan, A.; Rosen, D. M.; Ghandehari, H.; Denmeade, S. R. A prostate-specific antigen activated N-(2-hydroxypropyl) methacrylamide copolymer prodrug as dual-targeted therapy for prostate cancer. Mol. Cancer Ther., 2007, 6, 2928-2937. (Pubitemid 350206771)
142. Warnecke, A.; Fichtner, I.; Sass, G.; Kratz, F. Synthesis, cleavage profile, and antitumor efficacy of an albumin-binding prodrug of methotrexate that is cleaved by plasmin and cathepsin B. Arch. Pharm. (Weinheim), 2007, 340, 389-395. (Pubitemid 47291181)
143. Fiehn, C.; Kratz, F.; Sass, G.; Muller-Ladner, U.; Neumann, E. Targeted drug delivery by in vivo coupling to endogenous albumin: an albuminbinding prodrug of methotrexate (MTX) is better than MTX in the treatment of murine collagen-induced arthritis. Ann. Rheum. Dis., 2008, 67, 1188-1191.
144. Kratz, F.; Mansour, A.; Soltau, J.; Warnecke, A.; Fichtner, I.; Unger, C.; Drevs, J. Development of albumin-binding doxorubicin prodrugs that are cleaved by prostate-specific antigen. Arch. Pharm. (Weinheim), 2005, 338, 462-472. (Pubitemid 41564256)
145. Graeser, R.; Chung, D. E.; Esser, N.; Moor, S.; Schachtele, C.; Unger, C.; Kratz, F. Synthesis and biological evaluation of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen (PSA) in a PSApositive orthotopic prostate carcinoma model (LNCaP). Int. J Cancer, 2008, 122, 1145-1154. (Pubitemid 351222535)
146. Chung, D. E.; Kratz, F. Development of a novel albumin-binding prodrug that is cleaved by urokinase-type-plasminogen activator (uPA). Bioorg. Med. Chem Lett., 2006, 16, 5157-5163. (Pubitemid 44247692)
147. Kratz, F.; Drevs, J.; Bing, G.; Stockmar, C.; Scheuermann, K.; Lazar, P.; Unger, C. Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates. Bioorg. Med. Chem Lett., 2001, 11, 2001-2006. (Pubitemid 32709711)
148. Mansour, A. M.; Drevs, J.; Esser, N.; Hamada, F. M.; Badary, O. A.; Unger, C.; Fichtner, I.; Kratz, F. A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res., 2003, 63, 4062-4066. (Pubitemid 36917928)
149. Chau, Y.; Tan, F. E.; Langer, R. Synthesis and characterization of dextranpeptide- methotrexate conjugates for tumor targeting via mediation by matrix metalloproteinase II and matrix metalloproteinase IX. Bioconjug. Chem, 2004, 15, 931-941. (Pubitemid 38981971)
150. Liu, S.; Bugge, T. H.; Leppla, S. H. Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin. J Biol. Chem, 2001, 276, 17976-17984.
151. Abi-Habib, R. J.; Singh, R.; Liu, S.; Bugge, T. H.; Leppla, S. H.; Frankel, A. E. A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types. Mol. Cancer Ther., 2006, 5, 2556-2562. (Pubitemid 44650920)
152. Abi-Habib, R. J.; Singh, R.; Leppla, S. H.; Greene, J. J.; Ding, Y.; Berghuis, B.; Duesbery, N. S.; Frankel, A. E. Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice. Clin. Cancer Res., 2006, 12, 7437-7443. (Pubitemid 46095419)
153. Raeber, G. P.; Lutolf, M. P.; Hubbell, J. A. Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. Biophys. J, 2005, 89, 1374-1388. (Pubitemid 41099019)
154. Raeber, G. P.; Lutolf, M. P.; Hubbell, J. A. Part II: fibroblasts preferentially migrate in the direction of principal strain. Biomech. Model. Mechanobiol., 2008, 7, 215-225. (Pubitemid 351768573)
155. Raeber, G. P.; Lutolf, M. P.; Hubbell, J. A. Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. Biophys. J, 2005, 89, 1374-1388. (Pubitemid 41099019)
156. Seliktar, D.; Zisch, A. H.; Lutolf, M. P.; Wrana, J. L.; Hubbell, J. A. MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. J. Biomed. Mater. Res. A, 2004, 68, 704-716. (Pubitemid 38263935)
157. de Groot, F. M.; Broxterman, H. J.; Adams, H. P.; van Vliet, A.; Tesser, G. I.; Elderkamp, Y. W.; Schraa, A. J.; Kok, R. J.; Molema, G.; Pinedo, H. M.; Scheeren, H. W. Design, synthesis, and biological evaluation of a dual tumor-specific motive containing integrin-targeted plasmin-cleavable doxorubicin prodrug. Mol. Cancer Ther., 2002, 1, 901-911.
158. Hopewel, J. W.; Duncan, R.; Wilding, D.; Chakrabarti, K. Preclinical evaluation of the cardiotoxicity of PK2: a novel HPMA copolymerdoxorubicin- galactosamine conjugate antitumour agent. Hum. Exp. Toxicol., 2001, 20, 461-470.
159. Rao, J.; Dragulescu-Andrasi, A.; Yao, H. Fluorescence imaging in vivo: recent advances. Curr. Opin. Biotechnol., 2007, 18, 17-25. (Pubitemid 46237739)
160. Lange, N.; Jichlinski, P.; Zellweger, M.; Forrer, M.; Marti, A.; Guillou, L.; Kucera, P.; Wagnieres, G.; van den, B. H. Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study. Br. J Cancer, 1999, 80, 185-193. (Pubitemid 29210105)
161. Jocham, D.; Witjes, F.; Wagner, S.; Zeylemaker, B.; van Moorselaar, J.; Grimm, M. O.; Muschter, R.; Popken, G.; Konig, F.; Knuchel, R.; Kurth, K. H. Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urol., 2005, 174, 862-866. (Pubitemid 41140613)
162. Folli, S.; Wagnieres, G.; Pelegrin, A.; Calmes, J. M.; Braichotte, D.; Buchegger, F.; Chalandon, Y.; Hardman, N.; Heusser, C.; Givel, J. C.; . Immunophotodiagnosis of colon carcinomas in patients injected with fluoresceinated chimeric antibodies against carcinoembryonic antigen. Proc. Natl. Acad. Sci. U. S. A, 1992, 89, 7973-7977.
163. Förster Thomas. Fluorescence resonance energy transfer (FRET). Discussions Faraday Soc., 1959, 27
164. Selvin, P. R. The renaissance of fluorescence resonance energy transfer. Nat. Struct. Biol., 2000, 7, 730-734.
165. Matayoshi, E. D.; Wang, G. T.; Krafft, G. A.; Erickson, J. Novel fluorogenic substrates for assaying retroviral proteases by resonance energy transfer. Science, 1990, 247, 954-958.
166. Knight, C. G. Fluorimetric assays of proteolytic enzymes. Methods Enzymol., 1995, 248, 18-34.
167. Jiang, T.; Olson, E. S.; Nguyen, Q. T.; Roy, M.; Jennings, P. A.; Tsien, R. Y. Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc. Natl. Acad. Sci. U. S. A, 2004, 101, 17867-17872. (Pubitemid 40051978)
168. Jones, L. J.; Upson, R. H.; Haugland, R. P.; Panchuk-Voloshina, N.; Zhou, M.; Haugland, R. P. Quenched BODIPY dye-labeled casein substrates for the assay of protease activity by direct fluorescence measurement. Anal. Biochem., 1997, 251, 144-152. (Pubitemid 27392671)
169. Sameni, M.; Moin, K.; Sloane, B. F. Imaging proteolysis by living human breast cancer cells. Neoplasia, 2000, 2, 496-504. (Pubitemid 32098684)
170. Sameni, M.; Dosescu, J.; Sloane, B. F. Imaging proteolysis by living human glioma cells. Biol. Chem., 2001, 382, 785-788. (Pubitemid 32631715)
171. Weissleder, R.; Tung, C. H.; Mahmood, U.; Bogdanov, A., Jr. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat. Biotechnol., 1999, 17, 375-378. (Pubitemid 29166041)
172. Marecos, E.; Weissleder, R.; Bogdanov, A., Jr. Antibody-mediated versus nontargeted delivery in a human small cell lung carcinoma model. Bioconjug. Chem, 1998, 9, 184-191. (Pubitemid 28147135)
173. Bogdanov, A. A. Jr.; Weissleder, R.; Brady, T. J. Protected angiopolymers for vascular imaging. Handbook of Targeted Delivery of Imaging Agents, CRC-Press, 1995, pp. 501-522.
174. Weissleder, R.; Cheng, H. C.; Marecos, E.; Kwong, K.; Bogdanov, A., Jr. Non-invasive in vivo mapping of tumour vascular and interstitial volume fractions. Eur. J. Cancer, 1998, 34, 1448-1454. (Pubitemid 28370939)
175. Callahan, R. J.; Bogdanov, A., Jr.; Fischman, A. J.; Brady, T. J.; Weissleder, R. Preclinical evaluation and phase I clinical trial of a 99mTc-labeled synthetic polymer used in blood pool imaging. Am. J. Roentgenol., 1998, 171, 137-143. (Pubitemid 28308663)
176. Bogdanov, A. A., Jr.; Lin, C. P.; Simonova, M.; Matuszewski, L.; Weissleder, R. Cellular activation of the self-quenched fluorescent reporter probe in tumor microenvironment. Neoplasia., 2002, 4, 228-236. (Pubitemid 34525254)
177. Wunder, A.; Tung, C. H.; Muller-Ladner, U.; Weissleder, R.; Mahmood, U. In vivo imaging of protease activity in arthritis: a novel approach for monitoring treatment response. Arthritis Rheum., 2004, 50, 2459-2465. (Pubitemid 39062705)
178. Izmailova, E. S.; Paz, N.; Alencar, H.; Chun, M.; Schopf, L.; Hepperle, M.; Lane, J. H.; Harriman, G.; Xu, Y.; Ocain, T.; Weissleder, R.; Mahmood, U.; Healy, A. M.; Jaffee, B. Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in murine arthritis. Arthritis Rheum., 2007, 56, 117-128. (Pubitemid 46106184)
179. Grimm, J.; Kirsch, D. G.; Windsor, S. D.; Kim, C. F.; Santiago, P. M.; Ntziachristos, V.; Jacks, T.; Weissleder, R. Use of gene expression profiling to direct in vivo molecular imaging of lung cancer. Proc. Natl. Acad. Sci. U.S.A., 2005, 102, 14404-14409. (Pubitemid 41429710)
180. Funovics, M. A.; Alencar, H.; Montet, X.; Weissleder, R.; Mahmood, U. Simultaneous fluorescence imaging of protease expression and vascularity during murine colonoscopy for colonic lesion characterization. Gastrointest. Endosc., 2006, 64, 589-597. (Pubitemid 44397063)
181. Alencar, H.; Funovics, M. A.; Figueiredo, J.; Sawaya, H.; Weissleder, R.; Mahmood, U. Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for early detection--study in mice. Radiology, 2007, 244, 232-238. (Pubitemid 46981978)
182. Gounaris, E.; Tung, C. H.; Restaino, C.; Maehr, R.; Kohler, R.; Joyce, J. A.; Plough, H. L.; Barrett, T. A.; Weissleder, R.; Khazaie, K. Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth. PLoS ONE, 2008, 3, e2916
183. Marten, K.; Bremer, C.; Khazaie, K.; Sameni, M.; Sloane, B.; Tung, C. H.; Weissleder, R. Detection of dysplastic intestinal adenomas using enzymesensing molecular beacons in mice. Gastroenterology, 2002, 122, 406-414. (Pubitemid 34116992)
184. Chen, J.; Tung, C. H.; Mahmood, U.; Ntziachristos, V.; Gyurko, R.; Fishman, M. C.; Huang, P. L.; Weissleder, R. In vivo imaging of proteolytic activity in atherosclerosis. Circulation, 2002, 105, 2766-2771. (Pubitemid 34615149)
185. Bremer, C.; Ntziachristos, V.; Weitkamp, B.; Theilmeier, G.; Heindel, W.; Weissleder, R. Optical imaging of spontaneous breast tumors using protease sensing 'smart' optical probes. Invest Radiol., 2005, 40, 321-327. (Pubitemid 40734559)
186. Bremer, C.; Tung, C. H.; Bogdanov, A., Jr.; Weissleder, R. Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes. Radiology, 2002, 222, 814-818. (Pubitemid 34218157)
187. Tung, C. H.; Bredow, S.; Mahmood, U.; Weissleder, R. Preparation of a cathepsin D sensitive near-infrared fluorescence probe for imaging. Bioconjug. Chem, 1999, 10, 892-896. (Pubitemid 29456379)
188. Tung, C. H.; Mahmood, U.; Bredow, S.; Weissleder, R. In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. Cancer Res., 2000, 60, 4953-4958.
189. Bremer, C.; Tung, C. H.; Weissleder, R. In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat. Med., 2001, 7, 743-748. (Pubitemid 32588033)
190. Bremer, C.; Bredow, S.; Mahmood, U.; Weissleder, R.; Tung, C. H. Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model. Radiology, 2001, 221, 523-529. (Pubitemid 33043440)
191. McIntyre, J. O.; Fingleton, B.; Wells, K. S.; Piston, D. W.; Lynch, C. C.; Gautam, S.; Matrisian, L. M. Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. Biochem. J., 2004, 377, 617-628. (Pubitemid 38228373)
192. Deguchi, J. O.; Aikawa, M.; Tung, C. H.; Aikawa, E.; Kim, D. E.; Ntziachristos, V.; Weissleder, R.; Libby, P. Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in macrophages in vivo. Circulation, 2006, 114, 55-62. (Pubitemid 44305275)
193. Law, B.; Curino, A.; Bugge, T. H.; Weissleder, R.; Tung, C. H. Design, synthesis, and characterization of urokinase plasminogen-activator-sensitive near-infrared reporter. Chem Biol., 2004, 11, 99-106. (Pubitemid 38203994)
194. Hsiao, J. K.; Law, B.; Weissleder, R.; Tung, C. H. In-vivo imaging of tumor associated urokinase-type plasminogen activator activity. J. Biomed. Opt., 2006, 11, 34013
195. Tung, C. H.; Gerszten, R. E.; Jaffer, F. A.; Weissleder, R. A novel nearinfrared fluorescence sensor for detection of thrombin activation in blood. Chembiochem., 2002, 3, 207-211. (Pubitemid 36004496)
196. Jaffer, F. A.; Tung, C. H.; Gerszten, R. E.; Weissleder, R. In vivo imaging of thrombin activity in experimental thrombi with thrombin-sensitive nearinfrared molecular probe. Arterioscler. Thromb. Vasc. Biol., 2002, 22, 1929-1935. (Pubitemid 35315784)
197. Messerli, S. M.; Prabhakar, S.; Tang, Y.; Shah, K.; Cortes, M. L.; Murthy, V.; Weissleder, R.; Breakefield, X. O.; Tung, C. H. A novel method for imaging apoptosis using a caspase-1 near-infrared fluorescent probe. Neoplasia., 2004, 6, 95-105. (Pubitemid 38544597)
198. Kozloff, K. M.; Quinti, L.; Tung, C.; Weissleder, R.; Mahmood, U. Noninvasive imaging of osteoclast activity via near-infrared cathepsin-K activatable optical probe. J. Musculoskelet. Neuronal. Interact., 2006, 6, 353 (Pubitemid 46099712)
199. Shah, K.; Tung, C. H.; Chang, C. H.; Slootweg, E.; O'Loughlin, T.; Breakefield, X. O.; Weissleder, R. In vivo imaging of HIV protease activity in amplicon vector-transduced gliomas. Cancer Res., 2004, 64, 273-278. (Pubitemid 38120261)
200. Shah, K.; Tung, C. H.; Yang, K.; Weissleder, R.; Breakefield, X. O. Inducible release of TRAIL fusion proteins from a proapoptotic form for tumor therapy. Cancer Res., 2004, 64, 3236-3242. (Pubitemid 38581428)
201. Kim, K.; Lee, M.; Park, H.; Kim, J. H.; Kim, S.; Chung, H.; Choi, K.; Kim, I. S.; Seong, B. L.; Kwon, I. C. Cell-permeable and biocompatible polymeric nanoparticles for apoptosis imaging. J. Am. Chem. Soc., 2006, 128, 3490-3491.
202. Mu, C. J.; Lavan, D. A.; Langer, R. S.; Zetter, B. R. Self-assembled gold nanoparticle molecular probes for detecting proteolytic activity in vivo. ACS Nano., 2010, 4, 1511-1520.
203. Olson, E. S.; Jiang, T.; Aguilera, T. A.; Nguyen, Q. T.; Ellies, L. G.; Scadeng, M.; Tsien, R. Y. Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proc. Natl. Acad. Sci. U. S. A, 2010, 107, 4311-4316.
204. Nguyen, Q. T.; Olson, E. S.; Aguilera, T. A.; Jiang, T.; Scadeng, M.; Ellies, L. G.; Tsien, R. Y. Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc. Natl. Acad. Sci. U. S. A, 2010, 107, 4317-4322.
205. Ochsner, M. Photophysical and photobiological processes in the photodynamic therapy of tumours. J. Photochem. Photobiol. B, 1997, 39, 1-18. (Pubitemid 27285576)
206. Dougherty, T. J.; Gomer, C. J.; Henderson, B. W.; Jori, G.; Kessel, D.; Korbelik, M.; Moan, J.; Peng, Q. Photodynamic therapy. J. Natl. Cancer Inst., 1998, 90, 889-905. (Pubitemid 28304157)
207. Stiel, H.; Marlow, I.; Roeder, B. Photophysical properties of the photosensitizer pheophorbide a studied at high photon flux densities. J. Photochem. Photobiol. B, 1993, 17, 181-186. (Pubitemid 23054642)
208. Hackbarth, S.; Ermilov, E. A.; Roeder, B. Interaction of Pheophorbide a molecules covalently linkedto DAB dendrimers. Optics Commun., 2005, 248, 295-306. (Pubitemid 40423173)
209. Ito, F.; Ishibashi, Y.; Khan, S. R.; Miyasaka, H.; Kameyama, K.; Morisue, M.; Satake, A.; Ogawa, K.; Kobuke, Y. Photoinduced electron transfer and excitation energy transfer in directly linked zinc porphyrin/zinc phthalocyanine composite. J. Phys. Chem. A, 2006, 110, 12734-12742. (Pubitemid 46065649)
210. Zheng, G.; Aoudia, M.; Lee , M. A.; Rodgers K.M.; Smith, T. J.; Dougherty, T. J.; Pandey, R. K. Chlorin-based symmetrical and unsymmetrical dimers with amide linkages: effects of the substituents on photodynamic and photophysical properties. J. Chem. Soc. Perkin Trans. 1, 2000, 3113-3121. (Pubitemid 35290652)
211. McCarthy, J. R.; Perez, J. M.; Bruckner, C.; Weissleder, R. Polymeric nanoparticle preparation that eradicates tumors. Nano Lett., 2005, 5, 2552-2556.
212. Li, H.; Marotta, D. E.; Kim, S.; Busch, T. M.; Wileyto, E. P.; Zheng, G. High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low-density lipoprotein nanoparticles. J. Biomed. Opt., 2005, 10, 41203
213. Chen, J.; Stefflova, K.; Niedre, M. J.; Wilson, B. C.; Chance, B.; Glickson, J. D.; Zheng, G. Protease-triggered photosensitizing beacon based on singlet oxygen quenching and activation. J. Am. Chem Soc., 2004, 126, 11450-11451. (Pubitemid 39244956)
214. Stefflova, K.; Chen, J.; Marotta, D.; Li, H.; Zheng, G. Photodynamic therapy agent with a built-in apoptosis sensor for evaluating its own therapeutic outcome in situ. J. Med. Chem, 2006, 49, 3850-3856. (Pubitemid 43967882)
215. Zheng, G.; Chen, J.; Stefflova, K.; Jarvi, M.; Li, H.; Wilson, B. C. Photodynamic molecular beacon as an activatable photosensitizer based on protease-controlled singlet oxygen quenching and activation. Proc. Natl. Acad. Sci. U. S. A, 2007, 104, 8989-8994. (Pubitemid 47175424)
216. Lo, P. C.; Chen, J.; Stefflova, K.; Warren, M. S.; Navab, R.; Bandarchi, B.; Mullins, S.; Tsao, M.; Cheng, J. D.; Zheng, G. Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers. J. Med. Chem., 2009, 52, 358-368.
217. Chen, J.; Liu, T. W.; Lo, P. C.; Wilson, B. C.; Zheng, G. "Zipper" Molecular Beacons: A Generalized Strategy to Optimize the Performance of Activatable Protease Probes. Bioconjug. Chem., 2009, 20, 1836-1842.
218. Choi, Y.; Weissleder, R.; Tung, C. H. Protease-mediated phototoxicity of a polylysine-chlorin(E6) conjugate. ChemMedChem., 2006, 1, 698-701.
219. Soukos, N. S.; Hamblin, M. R.; Hasan, T. The effect of charge on cellular uptake and phototoxicity of polylysine chlorin(e6) conjugates. Photochem. Photobiol., 1997, 65, 723-729.
220. Hamblin, M. R.; Miller, J. L.; Rizvi, I.; Ortel, B.; Maytin, E. V.; Hasan, T. Pegylation of a chlorin(e6) polymer conjugate increases tumor targeting of photosensitizer. Cancer Res., 2001, 61, 7155-7162. (Pubitemid 32946509)
221. Hamblin, M. R.; Miller, J. L.; Rizvi, I.; Loew, H. G.; Hasan, T. Pegylation of charged polymer-photosensitiser conjugates: effects on photodynamic efficacy. Br. J. Cancer, 2003, 89, 937-943. (Pubitemid 37175819)
222. Campo, M. A.; Gabriel, D.; Kucera, P.; Gurny, R.; Lange, N. Polymeric photosensitizer prodrugs for photodynamic therapy. Photochem. Photobiol., 2007, 83, 958-965. (Pubitemid 47087386)
223. Choi, Y.; Weissleder, R.; Tung, C. H. Selective antitumor effect of novel protease-mediated photodynamic agent. Cancer Res., 2006, 66, 7225-7229. (Pubitemid 44197702)
224. Gabriel, D.; Campo, M. A.; Gurny, R.; Lange, N. Tailoring proteasesensitive photodynamic agents to specific disease-associated enzymes. Bioconjug. Chem, 2007, 18, 1070-1077. (Pubitemid 47122626)
225. Gabriel, D.; Zuluaga, M.; Martinez, M. N.; Campo, M. A.; Lange, N. Urokinase-plasminogen sensitive polymeric photosensitizer prodrugs: Design, synthesis and in vitro evaluation. J. Drug Deliv. Sci. Technol. (JDDST), 2009
226. Gabriel, D.; Busso, N.; So, A.; van den Bergh, H.; Gurny, R.; Lange, N. Thrombin-sensitive photodynamic agents: a novel strategy for selective synovectomy in rheumatoid arthritis. J. Control Rel., 2009, 138(3), 225-234.