Hypoxic tumor microenvironment: Opportunities to develop targeted therapies

Biotechnology Advances

Volumn 34, Issue 5, 2016, Pages 803-812

  Patel, Akhil ^a   Sant, Shilpa ^a,b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b University of Pittsburgh   (United States)

Author keywords

HIF 1; Hypoxia; pH targeted; Physicochemical change; Solid tumor microenvironment; Targeted therapy

Indexed keywords

DRUG THERAPY; ENZYME ACTIVITY;

HIF-1; HYPOXIA; PHYSICO-CHEMICAL CHANGES; SOLID TUMORS; TARGETED THERAPY;

TUMORS;

DRUG; HYPOXIA; LITERATURE REVIEW; OXYGEN; PH; PHYSICOCHEMICAL PROPERTY; PROTEIN; TUMOR;

OXYGEN;

ANIMAL; HUMAN; METABOLISM; MOUSE; TUMOR CELL LINE; TUMOR HYPOXIA; TUMOR MICROENVIRONMENT;

ANIMALS; CELL LINE, TUMOR; HUMANS; MICE; OXYGEN; TUMOR HYPOXIA; TUMOR MICROENVIRONMENT;

EID: 84966649948     PISSN: 07349750     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biotechadv.2016.04.005     Document Type: Review

References (115)

1. Ahn, G.-O., Botting, K.J., Patterson, A.V., Ware, D.C., Tercel, M., Wilson, W.R., Radiolytic and cellular reduction of a novel hypoxia-activated cobalt(III) prodrug of a chloromethylbenzindoline DNA minor groove alkylator. Biochem. Pharmacol. 71 (2006), 1683–1694.
2. Amsberry, K., Borchardt, R., Amine prodrugs which utilize hydroxy amide lactonization. I. A potential redox-sensitive amide prodrug. Pharm. Res. 8 (1991), 323–330.
3. Belozerov, V.E., Van Meir, E.G., Hypoxia inducible factor-1: a novel target for cancer therapy. Anti-Cancer Drugs 16 (2005), 901–909.
4. 2 availability on human cancer. Nat. Rev. Cancer 8 (2008), 967–975.
5. Binley, K., Askham, Z., Martin, L., Spearman, H., Day, D., Kingsman, S. et al., Hypoxia-mediated tumour targeting. Gene Ther. 10 (2003), 540–549.
6. Birner, P., Schindl, M., Obermair, A., Plank, C., Breitenecker, G., Oberhuber, G., Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 60 (2000), 4693–4696.
7. Biswas, S.K., Gangi, L., Paul, S., Schioppa, T., Saccani, A., Sironi, M. et al., A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-κB and enhanced IRF-3/STAT1 activation). Blood 107 (2006), 2112–2122.
8. Blake, D., Naughton, D., Adams, G., Stratford, I., Morris, C., Jaffar, M. et al., Bioreductive conjugate for targeting a therapeutic agent. Google Patents, 1998.
9. Bonapace, L., Coissieux, M.-M., Wyckoff, J., Mertz, K.D., Varga, Z., Junt, T. et al., Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature 515 (2014), 130–133.
10. Brown, J.M., Giaccia, A.J., The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 58 (1998), 1408–1416.
11. Bruick, R.K., McKnight, S.L., A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294 (2001), 1337–1340.
12. Campbell, R.B., Fukumura, D., Brown, E.B., Mazzola, L.M., Izumi, Y., Jain, R.K. et al., Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. Cancer Res. 62 (2002), 6831–6836.
13. Carlisle, R., Coussios, C.-C., Mechanical approaches to oncological drug delivery. Ther. Deliv. 4 (2013), 1213–1215.
14. Cassier, P.A., Italiano, A., Gomez-Roca, C.A., Le Tourneau, C., Toulmonde, M., Cannarile, M.A. et al., CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 16 (2015), 949–956.
15. Chanmee, T., Ontong, P., Konno, K., Itano, N., Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel) 6 (2014), 1670–1690.
16. Choi, J.Y., Ramasamy, T., Tuan Hiep, T., Ku, S.K., Shin, B.S., Choi, H.-G. et al., Systemic delivery of axitinib with nanohybrid liposomal nanoparticles inhibits hypoxic tumor growth. J. Mater. Chem. B 3 (2015), 408–416.
17. Chowdhury, G., Junnotula, V., Daniels, J.S., Greenberg, M.M., Gates, K.S., DNA strand damage product analysis provides evidence that the tumor cell-specific cytotoxin tirapazamine produces hydroxyl radical and acts as a surrogate for O(2). J. Am. Chem. Soc. 129 (2007), 12870–12877.
18. DeNardo, D.G., Brennan, D.J., Rexhepaj, E., Ruffell, B., Shiao, S.L., Madden, S.F. et al., Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 1 (2011), 54–67.
19. Denny, W.A., Prodrug strategies in cancer therapy. Eur. J. Med. Chem. 36 (2001), 577–595.
20. Denny, W.A., Hypoxia-activated prodrugs in cancer therapy: progress to the clinic. Future Oncol. 6 (2010), 419–428.
21. Dhani, N., Fyles, A., Hedley, D., Milosevic, M., The clinical significance of hypoxia in human cancers. Semin. Nucl. Med. 45 (2015), 110–121.
22. Di Paolo, A., Bocci, G., Drug distribution in tumors: mechanisms, role in drug resistance, and methods for modification. Curr. Oncol. Rep. 9 (2007), 109–114.
23. Doedens, A.L., Stockmann, C., Rubinstein, M.P., Liao, D., Zhang, N., DeNardo, D.G. et al., Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res. 70 (2010), 7465–7475.
24. Dong, J., Xue, M., Zink, J.I., Functioning of nanovalves on polymer coated mesoporous silica nanoparticles. Nanoscale 5 (2013), 10300–10306.
25. Duan, J.-X., Jiao, H., Kaizerman, J., Stanton, T., Evans, J.W., Lan, L. et al., Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs. J. Med. Chem. 51 (2008), 2412–2420.
26. Epstein, A.C.R., Gleadle, J.M., McNeill, L.A., Hewitson, K.S., O'Rourke, J., Mole, D.R. et al., C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107 (2001), 43–54.
27. Fang, P.-A., Margolis, H.C., Conway, J.F., Simmer, J.P., Dickinson, G.H., Beniash, E., Cryogenic transmission electron microscopy study of amelogenin self-assembly at different pH. Cells Tissues Organs 194 (2011), 166–170.
28. Farokhimanesh, S., Rahbarizadeh, F., Rasaee, M.J., Kamali, A., Mashkani, B., Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting. Biotechnol. Prog. 26 (2010), 505–511.
29. Freeman, S., Jaffor, M., Stratford, I., Drug targeting. Google Patents, 2005.
30. Fukumura, D., Jain, R.K., Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J. Cell. Biochem. 101 (2007), 937–949.
31. Gharat, L., Taneja, R., Weerapreeyakul, N., Rege, B., Polli, J., Chikhale, P.J., Targeted drug delivery systems 6: intracellular bioreductive activation, uptake and transport of an anticancer drug delivery system across intestinal Caco-2 cell monolayers. Int. J. Pharm. 219 (2001), 1–10.
32. Gleadle, J., Ratcliffe, P., Hypoxia. eLS, 2001, John Wiley & Sons, Ltd.
33. Goenka, S., Sant, V., Sant, S., Graphene-based nanomaterials for drug delivery and tissue engineering. J. Control. Release 173 (2014), 75–88.
34. Griffiths, L., Binley, K., Iqball, S., Kan, O., Maxwell, P., Ratcliffe, P. et al., The macrophage — a novel system to deliver gene therapy to pathological hypoxia. Gene Ther. 7 (2000), 255–262.
35. Guertin, D.A., Sabatini, D.M., Defining the role of mTOR in cancer. Cancer Cell 12 (2007), 9–22.
36. Guzy, R.D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K.D. et al., Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 1 (2005), 401–408.
37. Hadjipanayi, E., Cheema, U., Mudera, V., Deng, D., Liu, W., Brown, R.A., First implantable device for hypoxia-mediated angiogenic induction. J. Control. Release 153 (2011), 217–224.
38. Harris, A.L., Hypoxia — a key regulatory factor in tumour growth. Nat. Rev. Cancer 2 (2002), 38–47.
39. Hashimi, S.M., Xu, T., Wei, M.Q., Violacein anticancer activity is enhanced under hypoxia. Oncol. Rep. 33 (2015), 1731–1736.
40. Hennemann, B., Beckmann, G., Eichelmann, A., Rehm, A., Andreesen, R., Phase I trial of adoptive immunotherapy of cancer patients using monocyte-derived macrophages activated with interferon gamma and lipopolysaccharide. Cancer Immunol. Immunother. 45 (1998), 250–256.
41. Höckel, M., Vaupel, P., Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J. Natl. Cancer Inst. 93 (2001), 266–276.
42. Höckel, M., Schlenger, K., Höckel, S., Vaupel, P., Hypoxic cervical cancers with low apoptotic index are highly aggressive. Cancer Res. 59 (1999), 4525–4528.
43. Hsiao, H.T., Xing, L., Deng, X., Sun, X., Ling, C.C., Li, G.C., Hypoxia-targeted triple suicide gene therapy radiosensitizes human colorectal cancer cells. Oncol. Rep. 32 (2014), 723–729.
44. Jaffar, M., Williams, K.J., Stratford, I.J., Bioreductive and gene therapy approaches to hypoxic diseases. Adv. Drug Deliv. Rev. 53 (2001), 217–228.
45. Jiang, B.H., Rue, E., Wang, G.L., Roe, R., Semenza, G.L., Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J. Biol. Chem. 271 (1996), 17771–17778.
46. Kaur, B., Khwaja, F.W., Severson, E.A., Matheny, S.L., Brat, D.J., Van Meir, E.G., Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro-Oncology 7 (2005), 134–153.
47. Kizaka-Kondoh, S., Tanaka, S., Harada, H., Hiraoka, M., The HIF-1-active microenvironment: an environmental target for cancer therapy. Adv. Drug Deliv. Rev. 61 (2009), 623–632.
48. Koçer, A., Walko, M., Bulten, E., Halza, E., Feringa, B.L., Meijberg, W., Rationally designed chemical modulators convert a bacterial channel protein into a pH-sensory valve. Angew. Chem. Int. Ed. 45 (2006), 3126–3130.
49. Krishnamachary, B., Berg-Dixon, S., Kelly, B., Agani, F., Feldser, D., Ferreira, G. et al., Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res. 63 (2003), 1138–1143.
50. Le, Q.-T., Taira, A., Budenz, S., Jo Dorie, M., Goffinet, D.R., Fee, W.E. et al., Mature results from a randomized phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable stage IV head and neck squamous cell carcinomas. Cancer 106 (2006), 1940–1949.
51. Lee, K., Zhang, H., Qian, D.Z., Rey, S., Liu, J.O., Semenza, G.L., Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc. Natl. Acad. Sci. 106 (2009), 17910–17915.
52. Lee, S.-F., Zhu, X.-M., Wang, Y.-X.J., Xuan, S.-H., You, Q., Chan, W.-H. et al., Ultrasound, pH, and magnetically responsive crown-ether-coated core/shell nanoparticles as drug encapsulation and release systems. ACS Appl. Mater. Interfaces 5 (2013), 1566–1574.
53. Leek, R.D., Lewis, C.E., Whitehouse, R., Greenall, M., Clarke, J., Harris, A.L., Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 56 (1996), 4625–4629.
54. Levine, M.N., Raines, R.T., Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology. Chem. Sci. 3 (2012), 2412–2420.
55. Lewis, J.S., Landers, R.J., Underwood, J.C.E., Harris, A.L., Lewis, C.E., Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas. J. Pathol. 192 (2000), 150–158.
56. Liebler, D.C., The role of metabolism in the antioxidant function of vitamin E. Crit. Rev. Toxicol. 23 (1993), 147–169.
57. 64Cu liposomes. Biomaterials 33 (2012), 7785–7793.
58. Loges, S., Mazzone, M., Hohensinner, P., Carmeliet, P., Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell 15 (2009), 167–170.
59. Mack, P.C., Redman, M.W., Chansky, K., Williamson, S.K., Farneth, N.C., Lara, P.N. et al., Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J. Clin. Oncol. 26 (2008), 4771–4776.
60. Maeda, H., Fang, J., Inutsuka, T., Kitamoto, Y., Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. Int. Immunopharmacol. 3 (2003), 319–328.
61. Mason, D., Chen, Y.-Z., Krishnan, H.V., Sant, S., Cardiac gene therapy: recent advances and future directions. J. Control. Release 215 (2015), 101–111.
62. Meng, H., Xue, M., Xia, T., Zhao, Y.-L., Tamanoi, F., Stoddart, J.F. et al., Autonomous in vitro anticancer drug release from mesoporous silica nanoparticles by pH-sensitive nanovalves. J. Am. Chem. Soc. 132 (2010), 12690–12697.
63. Milane, L., Ganesh, S., Shah, S., Duan, Z.F., Amiji, M., Multi-modal strategies for overcoming tumor drug resistance: hypoxia, the Warburg effect, stem cells, and multifunctional nanotechnology. J. Control. Release 155 (2011), 237–247.
64. Minchinton, A.I., Tannock, I.F., Drug penetration in solid tumours. Nat. Rev. Cancer 6 (2006), 583–592.
65. Mizuno, T., Nagao, M., Yamada, Y., Narikiyo, M., Ueno, M., Miyagishi, M. et al., Small interfering RNA expression vector targeting hypoxia-inducible factor 1 alpha inhibits tumor growth in hepatobiliary and pancreatic cancers. Cancer Gene Ther. 13 (2005), 131–140.
66. Moon, C.Y., Choi, J.-W., Kasala, D., Jung, S.-J., Kim, S.W., Yun, C.-O., Dual tumor targeting with pH-sensitive and bioreducible polymer-complexed oncolytic adenovirus. Biomaterials 41 (2015), 53–68.
67. Murata, Y., Ohteki, T., Koyasu, S., Hamuro, J., IFN-gamma and pro-inflammatory cytokine production by antigen-presenting cells is dictated by intracellular thiol redox status regulated by oxygen tension. Eur. J. Immunol. 32 (2002), 2866–2873.
68. Murdoch, C., Giannoudis, A., Lewis, C.E., Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 104 (2004), 2224–2234.
69. Naughton, D.P., Drug targeting to hypoxic tissue using self-inactivating bioreductive delivery systems. Adv. Drug Deliv. Rev. 53 (2001), 229–233.
70. Nelson, D.A., Tan, T.-T., Rabson, A.B., Anderson, D., Degenhardt, K., White, E., Hypoxia and defective apoptosis drive genomic instability and tumorigenesis. Genes Dev. 18 (2004), 2095–2107.
71. Nguyen, T.D., Leung, K.C.-F., Liong, M., Pentecost, C.D., Stoddart, J.F., Zink, J.I., Construction of a pH-driven supramolecular nanovalve. Org. Lett. 8 (2006), 3363–3366.
72. Noy, R., Pollard, J.W., Tumor-associated macrophages: from mechanisms to therapy. Immunity 41 (2014), 49–61.
73. Obeid, E., Nanda, R., Fu, Y.-X., Olopade, O.I., The role of tumor-associated macrophages in breast cancer progression (review). Int. J. Oncol. 43 (2013), 5–12.
74. Oda, S., Oda, T., Nishi, K., Takabuchi, S., Wakamatsu, T., Tanaka, T. et al., Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner. PLoS One, 3, 2008, e2215.
75. Ojalvo, L.S., King, W., Cox, D., Pollard, J.W., High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am. J. Pathol. 174 (2009), 1048–1064.
76. Ostuni, R., Kratochvill, F., Murray, P.J., Natoli, G., Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol. 36 (2015), 229–239.
77. Parker, L.L., Lacy, S.M., Farrugia, L.J., Evans, C., Robins, D.J., O'Hare, C.C. et al., A novel design strategy for stable metal complexes of nitrogen mustards as bioreductive prodrugs. J. Med. Chem. 47 (2004), 5683–5689.
78. Patterson, A.V., Williams, K.J., Cowen, R.L., Jaffar, M., Telfer, B.A., Saunders, M. et al., Oxygen-sensitive enzyme-prodrug gene therapy for the eradication of radiation-resistant solid tumours. Gene Ther. 9 (2002), 946–954.
79. Patterson, A.V., Ferry, D.M., Edmunds, S.J., Gu, Y., Singleton, R.S., Patel, K. et al., Mechanism of action and preclinical antitumor activity of the novel hypoxia-activated DNA cross-linking agent PR-104. Clin. Cancer Res. 13 (2007), 3922–3932.
80. Pennacchietti, S., Michieli, P., Galluzzo, M., Mazzone, M., Giordano, S., Comoglio, P.M., Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3 (2003), 347–361.
81. Peters, K.B., Brown, J.M., Tirapazamine: a hypoxia-activated topoisomerase II poison. Cancer Res. 62 (2002), 5248–5253.
82. Poon, Z., Chang, D., Zhao, X., Hammond, P.T., Layer-by-layer nanoparticles with a pH-sheddable layer for in vivo targeting of tumor hypoxia. ACS Nano 5 (2011), 4284–4292.
83. Prabhakar, N.R., Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms. J. Appl. Physiol. (1985) 90 (2001), 1986–1994.
84. Qian, B.-Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L.R. et al., CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475 (2011), 222–225.
85. Rhim, T., Lee, D.Y., Lee, M., Hypoxia as a target for tissue specific gene therapy. J. Control. Release 172 (2013), 484–494.
86. Rischin, D., Peters, L., Hicks, R., Hughes, P., Fisher, R., Hart, R. et al., Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. J. Clin. Oncol. 19 (2001), 535–542.
87. Rischin, D., Peters, L., Fisher, R., Macann, A., Denham, J., Poulsen, M. et al., Tirapazamine, cisplatin, and radiation versus fluorouracil, cisplatin, and radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02). J. Clin. Oncol. 23 (2005), 79–87.
88. + T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 26 (2014), 623–637.
89. Saito, G., Swanson, J.A., Lee, K.-D., Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv. Drug Deliv. Rev. 55 (2003), 199–215.
90. Sant, S., Nadeau, W., Hildgen, P., Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA nanoparticles. J. Control. Release 107 (2005), 203–214.
91. Sant, S., Poulin, S., Hildgen, P., Effect of polymer architecture on surface properties, plasma protein adsorption, and cellular interactions of pegylated nanoparticles. J. Biomed. Mater. Res. A 87A (2008), 885–895.
92. Sant, S., Thommes, M., Hildgen, P., Microporous structure and drug release kinetics of polymeric nanoparticles. Langmuir 24 (2008), 280–287.
93. Semenza, G.L., Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3 (2003), 721–732.
94. Shibata, T., Giaccia, A.J., Brown, J.M., Hypoxia-inducible regulation of a prodrug-activating enzyme for tumor-specific gene therapy. Neoplasia 4 (2002), 40–48.
95. Shinde, S.S., Hay, M.P., Patterson, A.V., Denny, W.A., Anderson, R.F., Spin trapping of radicals other than the [rad]OH radical upon reduction of the anticancer agent tirapazamine by cytochrome P450 reductase. J. Am. Chem. Soc. 131 (2009), 14220–14221.
96. Singh, M., Close, D.A., Mukundan, S., Johnston, P.A., Sant, S., Production of uniform 3D microtumorsin hydrogel microwell arrays for measurement of viability, morphology, and signaling pathway activation.. Assay Drug Dev Technol 13 (2015), 570–583.
97. Singh, M., Mukundan, S., Jaramillo, M., Oesterreich, S., Sant, S., Three-]dimensional breast cancer models mimic hallmarks of size-induced tumorprogression. Cancer Res, 2016 (in press).
98. Subarsky, P., Hill, R.P., The hypoxic tumour microenvironment and metastatic progression. Clin. Exp. Metastasis 20 (2003), 237–250.
99. Sun, X., Vale, M., Jiang, X., Gupta, R., Krissansen, G.W., Antisense HIF-1[alpha] prevents acquired tumor resistance to angiostatin gene therapy. Cancer Gene Ther. 17 (2010), 532–540.
100. Thomlinson, R.H., Gray, L.H., The histological structure of some human lung cancers and the possible implications for radiotherapy. Br. J. Cancer 9 (1955), 539–549.
101. Tian, L., Bae, Y.H., Cancer nanomedicines targeting tumor extracellular pH. Colloids Surf. B Biointerfaces 99 (2012), 116–126.
102. Torroella-Kouri, M., Silvera, R., Rodriguez, D., Caso, R., Shatry, A., Opiela, S. et al., Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Res. 69 (2009), 4800–4809.
103. Turner, L., Scotton, C., Negus, R., Balkwill, F., Hypoxia inhibits macrophage migration. Eur. J. Immunol. 29 (1999), 2280–2287.
104. van Vlerken, L.E., Duan, Z., Seiden, M.V., Amiji, M.M., Modulation of intracellular ceramide using polymeric nanoparticles to overcome multidrug resistance in cancer. Cancer Res. 67 (2007), 4843–4850.
105. Vaupel, P., Mayer, A., Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 26 (2007), 225–239.
106. von Pawel, J., von Roemeling, R., Gatzemeier, U., Boyer, M., Elisson, L.O., Clark, P. et al., Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: a report of the international CATAPULT I study group. Cisplatin and tirapazamine in subjects with advanced previously untreated non-small-cell lung tumors. J. Clin. Oncol. 18 (2000), 1351–1359.
107. Ware, D.C., Palmer, B.D., Wilson, W.R., Denny, W.A., Hypoxia-selective antitumor agents. 7. Metal complexes of aliphatic mustards as a new class of hypoxia-selective cytotoxins. Synthesis and evaluation of cobalt(III) complexes of bidentate mustards. J. Med. Chem. 36 (1993), 1839–1846.
108. Williamson, S.K., Crowley, J.J., Lara, P.N., McCoy, J., Lau, D.H.M., Tucker, R.W. et al., Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group trial S0003. J. Clin. Oncol. 23 (2005), 9097–9104.
109. Wilson, W.R., Hay, M.P., Targeting hypoxia in cancer therapy. Nat. Rev. Cancer 11 (2011), 393–410.
110. Wouters, B.G., Koritzinsky, M., Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat. Rev. Cancer 8 (2008), 851–864.
111. Xia, Y., Choi, H.-K., Lee, K., Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur. J. Med. Chem. 49 (2012), 24–40.
112. Xue, M., Findenegg, G.H., Lysozyme as a pH-responsive valve for the controlled release of guest molecules from mesoporous silica. Langmuir 28 (2012), 17578–17584.
113. Xue, M., Zhong, X., Shaposhnik, Z., Qu, Y., Tamanoi, F., Duan, X. et al., pH-Operated mechanized porous silicon nanoparticles. J. Am. Chem. Soc. 133 (2011), 8798–8801.
114. Yu, W., Liu, C., Liu, Y., Zhang, N., Xu, W., Mannan-modified solid lipid nanoparticles for targeted gene delivery to alveolar macrophages. Pharm. Res. 27 (2010), 1584–1596.
115. Zhu, S., Niu, M., O'Mary, H., Cui, Z., Targeting of tumor-associated macrophages made possible by PEG-sheddable, mannose-modified nanoparticles. Mol. Pharm. 10 (2013), 3525–3530.