Nanoparticle delivery strategies to target doxorubicin to tumor cells and reduce side effects

Therapeutic Delivery

Volumn 1, Issue 2, 2010, Pages 273-287

  Wang, Yiguang ^a   Wei, Xiuli ^a   Zhang, Chunling ^a   Zhang, Fayun ^a   Liang, Wei ^a  

^a INSTITUTE OF BIOPHYSICS   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; COMBRETASTATIN; CYCLOPHOSPHAMIDE; DENDRIMER; DOXORUBICIN; LIPOSOME; MACROGOL; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 2C5; NANOPARTICLE; PACLITAXEL; PHOSPHATIDYLETHANOLAMINE; POLYCAPROLACTONE; POLYMER; UNCLASSIFIED DRUG;

ADVERSE OUTCOME; BLOOD TOXICITY; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER RESISTANCE; CARDIOTOXICITY; COLON CARCINOMA; CONTROLLED DRUG RELEASE; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CYTOTOXICITY; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG PENETRATION; DRUG SAFETY; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG STABILITY; DRUG TARGETING; DRUG TOLERABILITY; DRUG UPTAKE; ESOPHAGEAL ADENOCARCINOMA; GASTROINTESTINAL CARCINOMA; HAND FOOT SYNDROME; HUMAN; KAPOSI SARCOMA; LEWIS CARCINOMA; LUNG CANCER; METASTASIS; MICELLE; MULTIDRUG RESISTANCE; NANOENCAPSULATION; NANOPHARMACEUTICS; NEUROBLASTOMA; NEUTROPENIA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE; SKIN TOXICITY; SOLID TUMOR; STOMACH CANCER; TREATMENT PLANNING; ULTRASOUND THERAPY;

EID: 79955042843     PISSN: 20415990     EISSN: 20416008     Source Type: Journal    
DOI: 10.4155/tde.10.24     Document Type: Review

References (102)

1. Hortobagyi GN. Anthracyclines in the treatment of cancer. An overview. Drugs. 54 (Suppl. 4), 1-7 (1997). (Pubitemid 27487789)
2. Maluf FC, Spriggs D. Anthracyclines in the treatment of gynecologic malignancies. Gynecol. Oncol. 85(1), 18-31 (2002). (Pubitemid 34304005)
3. Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the anti-tumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol. 57(7), 727-741 (1999). (Pubitemid 29094544)
4. Olson RD, Mushlin PS. Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. FASEB J. 4(13), 3076-3086 (1990).
5. Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7(9), 771-782 (2008).
6. Peer D, Karp JM, Hong S et al. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2(12), 751-760 (2007). (Pubitemid 350223348)
7. Maeda H, Wu J, Sawa T et al. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control Release 65(1-2), 271-284 (2000). (Pubitemid 30122932)
8. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv. Drug Deliv. Rev. 60(15), 1615-1626 (2008).
9. Lammers T, Hennink WE, Storm G. Tumour-targeted nanomedicines: principles and practice. Br. J. Cancer. 99(3), 392-397 (2008).
10. Batist G, Barton J, Chaikin P et al. Myocet (liposome-encapsulated doxorubicin citrate): a new approach in breast cancer therapy. Expert Opin. Pharmacother. 3(12), 1739-1751 (2002). (Pubitemid 36054595)
11. Leonard RC, Williams S, Tulpule A et al. Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet). Breast. 18(4), 218-224 (2009).
12. James ND, Coker RJ, Tomlinson D et al. Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS. Clin. Oncol. (R. Coll. Radiol.) 6(5), 294-296 (1994). (Pubitemid 24310395)
13. Tejada-Berges T, Granai CO, Gordinier M et al. Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Expert Rev. Anticancer Ther. 2(2), 143-150 (2002). (Pubitemid 34679469)
14. Sutton D, Nasongkla N, Blanco E et al. Functionalized micellar systems for cancer targeted drug delivery. Pharm. Res. 24(6), 1029-1046 (2007). (Pubitemid 46798882)
15. Sparano JA, Winer EP. Liposomal anthracyclines for breast cancer. Semin. Oncol. 28(4 Suppl. 12), 32-40 (2001). (Pubitemid 32879937)
16. Batist G, Ramakrishnan G, Rao CS et al. Reduced cardiotoxicity and preserved anti-tumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J. Clin. Oncol. 19(5), 1444-1454 (2001). (Pubitemid 32202552)
17. Harris L, Batist G, Belt R et al. Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer. 94(1), 25-36 (2002). (Pubitemid 34049039)
18. Chan S, Davidson N, Juozaityte E et al. Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. Ann. Oncol. 15(10), 1527-1534 (2004). (Pubitemid 39409744)
19. Elbayoumi TA, Torchilin VP. Tumor-specific antibody-mediated targeted delivery of Doxil reduces the manifestation of auricular erythema side effect in mice. Int. J. Pharm. 357(1-2), 272-279 (2008).
20. Cheng WW, Allen TM. Targeted delivery of anti-CD19 liposomal doxorubicin in B-cell lymphoma: a comparison of whole monoclonal antibody, Fab' fragments and single chain Fv. J. Control Release. 126(1), 50-58 (2008).
21. Yamada A, Taniguchi Y, Kawano K et al. Design of folate-linked liposomal doxorubicin to its anti-tumor effect in mice. Clin. Cancer Res. 14(24), 8161-8168 (2008).
22. Schiffelers RM, Koning GA, ten Hagen TL et al. Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. J. Control Release. 91(1-2), 115-122 (2003). (Pubitemid 37288882)
23. Allen TM, Mumbengegwi DR, Charrois GJ. Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates. Clin. Cancer Res. 11(9), 3567-3573 (2005). (Pubitemid 40627913)
24. Pastorino F, Brignole C, Marimpietri D et al. Doxorubicin-loaded Fab' fragments of anti-disialoganglioside immunoliposomes selectively inhibit the growth and dissemination of human neuroblastoma in nude mice. Cancer Res. 63(1), 86-92 (2003). (Pubitemid 36070424)
25. Murphy EA, Majeti BK, Barnes LA et al. Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis. Proc. Natl Acad. Sci. USA 105(27), 9343-9348 (2008).
26. Lee TY, Lin CT, Kuo SY et al. Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery. Cancer Res. 67(22), 10958-10965 (2007).
27. Moreira JN, Gaspar R. Antagonist G-mediated targeting and cytotoxicity of liposomal doxorubicin in NCI-H82 variant small cell lung cancer. Braz. J. Med. Biol. Res. 37(8), 1185-1192 (2004). (Pubitemid 39172552)
28. Kobayashi T, Ishida T, Okada Y et al. Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells. Int. J. Pharm. 329(1-2), 94-102 (2007). (Pubitemid 44937528)
29. Saul JM, Annapragada A, Natarajan JV et al. Controlled targeting of liposomal doxorubicin via the folate receptor in vitro. J. Control Release. 92(1-2), 49-67 (2003). (Pubitemid 37130121)
30. Gabizon A, Tzemach D, Gorin J et al. Improved therapeutic activity of folate-targeted liposomal doxorubicin in folate receptor-expressing tumor models. Cancer Chemother. Pharmacol. 66(1), 43-52 (2010).
31. Peer D, Margalit R. Tumor-targeted hyaluronan nanoliposomes increase the anti-tumor activity of liposomal doxorubicin in syngeneic and human xenograft mouse tumor models. Neoplasia. 6(4), 343-353 (2004). (Pubitemid 38924849)
32. Eliaz RE, Szoka FC Jr. Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44-overexpressing tumor cells. Cancer Res. 61(6), 2592-2601 (2001). (Pubitemid 32685844)
33. Song CK, Jung SH, Kim DD et al. Disaccharide-modified liposomes and their in vitro intracellular uptake. Int. J. Pharm. 380(1-2), 161-169 (2009).
34. Elbayoumi TA, Torchilin VP. Enhanced cytotoxicity of monoclonal anticancer antibody 2C5-modified doxorubicin-loaded PEGylated liposomes against various tumor cell lines. Eur. J. Pharm. Sci. 32(3), 159-168 (2007). (Pubitemid 47532709)
35. Lukyanov AN, Elbayoumi TA, Chakilam AR et al. Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody. J. Control Release. 100(1), 135-144 (2004). (Pubitemid 39445991)
36. Elbayoumi TA, Pabba S, Roby A et al. Antinucleosome antibody-modified liposomes and lipid-core micelles for tumor-targeted delivery of therapeutic and diagnostic agents. J. Liposome Res. 17(1), 1-14 (2007). (Pubitemid 46631140)
37. Elbayoumi TA, Torchilin VP. Tumor-specific anti-nucleosome antibody improves therapeutic efficacy of doxorubicin-loaded long-circulating liposomes against primary and metastatic tumor in mice. Mol. Pharm. 6(1), 246-254 (2009).
38. Elbayoumi TA, Torchilin VP. Tumor-targeted nanomedicines: enhanced anti-tumor efficacy in vivo of doxorubicin-loaded, long-circulating liposomes modified with cancer-specific monoclonal antibody. Clin. Cancer Res. 15(6), 1973-1980 (2009).
39. Pastorino F, Brignole C, Marimpietri D et al. Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. Cancer Res. 63(21), 7400-7409 (2003). (Pubitemid 37413482)
40. Pastorino F, Brignole C, Di Paolo D et al. Targeting liposomal chemotherapy via both tumor cell-specific and tumor vasculature-specific ligands potentiates therapeutic efficacy. Cancer Res. 66(20), 10073-10082 (2006). (Pubitemid 44672061)
41. Loi M, Marchio S, Becherini P et al. Combined targeting of perivascular and endothelial tumor cells enhances anti-tumor efficacy of liposomal chemotherapy in neuroblastoma. J. Control Release. 145(1), 66-73 (2010).
42. Longmuir KJ, Haynes SM, Baratta JL et al. Liposomal delivery of doxorubicin to hepatocytes in vivo by targeting heparan sulfate. Int. J. Pharm. 382(1-2), 222-233 (2009).
43. Cheong I, Huang X, Bettegowda C et al. A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science. 314(5803), 1308-1311 (2006). (Pubitemid 44846406)
44. Cheong I, Huang X, Thornton K et al. Targeting cancer with bugs and liposomes: ready, aim, fire. Cancer Res. 67(20), 9605-9608 (2007). (Pubitemid 47621203)
45. Wang Y, Wang R, Lu X et al. Pegylated phospholipids-based self-assembly with water-soluble drugs. Pharm. Res. 27(2), 361-370 (2010).
46. Matsumura Y, Hamaguchi T, Ura T et al. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br. J. Cancer. 91(10), 1775-1781 (2004). (Pubitemid 39664964)
47. Kuroda J, Kuratsu J, Yasunaga M et al. Potent antitumor effect of SN-38-incorporating polymeric micelle, NK012, against malignant glioma. Int. J. Cancer. 124(11), 2505-2511 (2009).
48. Matsumura Y. Poly (amino acid) micelle nanocarriers in preclinical and clinical studies. Adv. Drug Deliv. Rev. 60(8), 899-914 (2008).
49. Danson S, Ferry D, Alakhov V et al. Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer. Br. J. Cancer. 90(11), 2085-2091 (2004). (Pubitemid 38869710)
50. Kim DW, Kim SY, Kim HK et al. Multicenter Phase II trial of Genexol-PM, a novel Cremophor-free, polymeric micelle formulation of paclitaxel, with cisplatin in patients with advanced non-small-cell lung cancer. Ann. Oncol. 18(12), 2009-2014 (2007).
51. Lee KS, Chung HC, Im SA et al. Multicenter Phase II trial of Genexol-PM, a cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer. Breast Cancer Res. Treat. 108(2), 241-250 (2008). (Pubitemid 351311357)
52. Valle JW, Armstrong A, Newman C et al. A Phase II study of SP1049C, doxorubicin in P-glycoprotein-targeting pluronics, in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction. Invest New Drugs. DOI: 10.1007/s10637- 010-9399-9391 (2010) (Epub ahead of print).
53. Tang N, Du G, Wang N et al. Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin. J. Natl Cancer Inst. 99(13), 1004-1015 (2007). (Pubitemid 47232602)
54. Tsukioka Y, Matsumura Y, Hamaguchi T et al. Pharmaceutical and biomedical differences between micellar doxorubicin (NK911) and liposomal doxorubicin (Doxil). Jpn J. Cancer Res. 93(10), 1145-1153 (2002). (Pubitemid 35314960)
55. Yoo HS, Park TG. Folate receptor targeted biodegradable polymeric doxorubicin micelles. J. Control Release. 96(2), 273-283 (2004). (Pubitemid 38481509)
56. Yoo HS, Park TG. Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin-PEG-folate conjugate. J. Control Release. 100(2), 247-256 (2004). (Pubitemid 39491276)
57. Tsai HC, Chang WH, Lo CL et al. Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging. Biomaterials 31(8), 2293-2301 (2010).
58. Kim D, Gao ZG, Lee ES et al. In vivo evaluation of doxorubicin-loaded polymeric micelles targeting folate receptors and early endosomal pH in drug-resistant ovarian cancer. Mol. Pharm. 6(5), 1353-1362 (2009).
59. Kim D, Lee ES, Oh KT et al. Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH. Small 4(11), 2043-2050 (2008).
60. Nasongkla N, Shuai X, Ai H et al. cRGD-functionalized polymer micelles for targeted doxorubicin delivery. Angew Chem. Int. Ed. Engl. 43(46), 6323-6327 (2004). (Pubitemid 40029462)
61. Nasongkla N, Bey E, Ren J et al. Multi functional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett. 6(11), 2427-2430 (2006). (Pubitemid 46076928)
62. Xiong XB, Ma Z, Lai R et al. The therapeutic response to multifunctional polymeric nano-conjugates in the targeted cellular and subcellular delivery of doxorubicin. Biomaterials 31(4), 757-768 (2010).
63. Kataoka K, Matsumoto T, Yokoyama M et al. Doxorubicin-loaded poly(ethylene glycol)- poly(b-benzyl-l-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance. J. Control Release 64(1-3), 143-153 (2000). (Pubitemid 30035315)
64. Bae Y, Nishiyama N, Fukushima S et al. Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo anti-tumor efficacy. Bioconjug. Chem. 16(1), 122-130 (2005). (Pubitemid 40129685)
65. Hruby M, Konak C, Ulbrich K. Polymeric micellar pH-sensitive drug-delivery system for doxorubicin. J. Control Release 103(1), 137-148 (2005). (Pubitemid 40248568)
66. Bae Y, Fukushima S, Harada A et al. Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change. Angew Chem. Int. Ed. Engl. 42(38), 4640-4643 (2003). (Pubitemid 37271305)
67. Bae Y, Jang WD, Nishiyama N et al. Multifunctional polymeric micelles with folate-mediated cancer cell targeting and pH-triggered drug releasing properties for active intracellular drug delivery. Mol. Biosyst. 1(3), 242-250 (2005). (Pubitemid 41442434)
68. Lee ES, Na K, Bae YH. Polymeric micelle for tumor pH and folate-mediated targeting. J. Control Release. 91(1-2), 103-113 (2003). (Pubitemid 37288881)
69. Lee ES, Na K, Bae YH. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. J. Control Release 103(2), 405-418 (2005). (Pubitemid 40342538)
70. Lee ES, Gao Z, Kim D et al. Super pH-sensitive multifunctional polymeric micelle for tumor pH(e) specific TAT exposure and multidrug resistance. J. Control Release 129(3), 228-236 (2008).
71. Lee ES, Na K, Bae YH. Super pH-sensitive multifunctional polymeric micelle. Nano Lett. 5(2), 325-329 (2005). (Pubitemid 40308294)
72. Sethuraman VA, Bae YH. TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors. J. Control Release. 118(2), 216-224 (2007). (Pubitemid 46350711)
73. Holmgren L, O'Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat. Med. 1(2), 149-153 (1995).
74. Satchi-Fainaro R, Puder M, Davies JW et al. Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470. Nat. Med. 10(3), 255-261 (2004). (Pubitemid 38667615)
75. Tozer GM, Kanthou C, Baguley BC. Disrupting tumour blood vessels. Nat. Rev. Cancer 5(6), 423-435 (2005). (Pubitemid 40791485)
76. Sengupta S, Eavarone D, Capila I et al. Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature 436(7050), 568-572 (2005). (Pubitemid 41112931)
77. Mooney D. Cancer: one step at a time. Nature 436, 468-469 (2005). (Pubitemid 41112900)
78. MacKay JA, Chen M, McDaniel JR et al. Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nat. Mater. 8(12), 993-999 (2009).
79. Park J, Fong PM, Lu J et al. PEGylated PLGA nanoparticles for the improved delivery of doxorubicin. Nanomedicine 5(4), 410-418 (2009).
80. Li YL, Zhu L, Liu Z et al. Reversibly stabilized multifunctional dextran nanoparticles efficiently deliver doxorubicin into the nuclei of cancer cells. Angew Chem. Int. Ed. Engl. 48(52), 9914-9918 (2009).
81. Maeng JH, Lee DH, Jung KH et al. Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. Biomaterials 31(18), 4995-5006 (2010).
82. Kim B, Han G, Toley BJ et al. Tuning payload delivery in tumour cylindroids using gold nanoparticles. Nat. Nanotechnol. 5, 465-472 (2010).
83. Duncan R. Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer. 6(9), 688-701 (2006). (Pubitemid 44286001)
84. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5(3), 161-171 (2005). (Pubitemid 40314948)
85. Gillies ER, Frechet JM. Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today 10(1), 35-43 (2005). (Pubitemid 40164817)
86. Lee CC, Gillies ER, Fox ME et al. A single dose of doxorubicin- functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas. Proc. Natl Acad. Sci. USA 103(45), 16649-16654 (2006). (Pubitemid 44737307)
87. Kono K, Kojima C, Hayashi N et al. Preparation and cytotoxic activity of poly(ethylene glycol)-modified poly(amidoamine) dendrimers bearing adriamycin. Biomaterials 29(11), 1664-1675 (2008).
88. Kaneshiro TL, Lu ZR. Targeted intracellular codelivery of chemotherapeutics and nucleic acid with a well-defined dendrimer-based nanoglobular carrier. Biomaterials 30(29), 5660-5666 (2009).
89. Rapoport N, Pitt WG, Sun H et al. Drug delivery in polymeric micelles: from in vitro to in vivo. J. Control Release 91(1-2), 85-95 (2003). (Pubitemid 37288879)
90. Husseini GA, Runyan CM, Pitt WG. Investigating the mechanism of acoustically activated uptake of drugs from Pluronic micelles. BMC Cancer 2, 20 (2002).
91. Marin A, Sun H, Husseini GA et al. Drug delivery in pluronic micelles: effect of high-frequency ultrasound on drug release from micelles and intracellular uptake. J. Control Release 84(1-2), 39-47 (2002). (Pubitemid 35223412)
92. Rapoport NY, Herron JN, Pitt WG et al. Micellar delivery of doxorubicin and its paramagnetic analog, ruboxyl, to HL-60 cells: effect of micelle structure and ultrasound on the intracellular drug uptake. J. Control Release 58(2), 153-162 (1999). (Pubitemid 29112886)
93. Ferrara KW. Driving delivery vehicles with ultrasound. Adv. Drug Deliv. Rev. 60(10), 1097-1102 (2008).
94. Frenkel V. Ultrasound mediated delivery of drugs and genes to solid tumors. Adv. Drug Deliv. Rev. 60(10), 1193-1208 (2008).
95. Vandenbroucke RE, Lentacker I, Demeester J et al. Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles. J. Control Release 126(3), 265-273 (2008).
96. Lentacker I, Vandenbroucke RE, Lucas B et al. New strategies for nucleic acid delivery to conquer cellular and nuclear membranes. J. Control Release. 132(3), 279-288 (2008).
97. Lentacker I, Geers B, Demeester J et al. Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved. Mol. Ther. 18(1), 101-108 (2010).
98. Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat. Rev. Cancer 4(6), 423-436 (2004). (Pubitemid 38745528)
99. Browder T, Butterfield CE, Kraling BM et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. 60(7), 1878-1886 (2000). (Pubitemid 30207647)
100. Italiano A, Toulmonde M, Lortal B et al. "Metronomic" chemotherapy in advanced soft tissue sarcomas. Cancer Chemother. Pharmacol. 66(1), 197-202 (2010).
101. Munzone E, Di Pietro A, Goldhirsch A et al. Metronomic administration of pegylated liposomal-doxorubicin in extensively pre-treated metastatic breast cancer patients: a mono-institutional case-series report. Breast 19(1), 33-37 (2010).
102. Allen TM, Cullis PR. Drug-delivery systems: entering the mainstream. Science 303(5665), 1818-1822 (2004).