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The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) IF: 2.7 To calculate the five year Impact Factor, citations are counted in 2017 to the previous five years and divided by the source items published in the previous five years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) 5-Year IF: 3.6 The Immediacy Index is the average number of times an article is cited in the year it is published. The journal Immediacy Index indicates how quickly articles in a journal are cited. Immediacy Index: 0.8 The Eigenfactor score, developed by Jevin West and Carl Bergstrom at the University of Washington, is a rating of the total importance of a scientific journal. Journals are rated according to the number of incoming citations, with citations from highly ranked journals weighted to make a larger contribution to the eigenfactor than those from poorly ranked journals. Eigenfactor: 0.00023 The Journal Citation Indicator (JCI) is a single measurement of the field-normalized citation impact of journals in the Web of Science Core Collection across disciplines. The key words here are that the metric is normalized and cross-disciplinary. JCI: 0.39 SJR: 0.42 SNIP: 0.89 CiteScore™:: 5.5 H-Index: 79

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Insight on Multidrug Resistance and Nanomedicine Approaches to Overcome MDR

卷 37, 册 5, 2020, pp. 473-509
DOI: 10.1615/CritRevTherDrugCarrierSyst.2020025052
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摘要

Multidrug resistance (MDR) remains a major obstacle to ensure effective chemotherapy in cancer patients. Several factors could be associated with cancer cells' drug resistance such as overexpression of P-glycoprotein (P-gp), cancer stem cells (CSCs), defect in apoptosis, mutation and alteration in DNA repair pathways, angiogenesis, autophagy, and modulation in metabolic enzymes. Until now, drug efflux by ABC transporters has been a univocal and well-established mechanism of chemotherapeutic associated drug resistance. To explore the mechanics involved in ABC transporter associated drug resistance, many crucial studies have been conducted from identification of drug binding sites to elucidation of their structure. Due to our continuous battle with drug resistance, several strategies have been employed to combat MDR, including P-gp modulators, siRNAs, antibodies, as well as peptides. Furthermore, various nanoparticle and different effective combination nanomedicine strategies also suggest some exciting results. Thus, to improve nanomedicine approaches to overcome MDR, in this evolutionary review, we have focused on fundamentals of possible strategies as well as the latest accomplishments to reverse MDR.

参考文献
  1. Dhas NL, Kudarha RR, Acharya NS, Acharya SR. Polymeric immunonanoparticles mediated cancer therapy: Versatile nanocarriers for cell-specific cargo delivery. Crit Rev Ther Drug Carrier Syst. 2018;35(1):1-64.

  2. Allen TM, Cullis PR. Drug delivery systems: Entering the mainstream. Science. 2004;303(5665):1818-22.

  3. Desai P, Ann D, Wang J, Prabhu S. Pancreatic cancer: Recent advances in nanoformulation-based therapies. Crit Rev Ther Drug Carrier Syst. 2019;36(1):59-91.

  4. Tsuruo T, Naito M, Tomida A, Fujita N, Mashima T, Sakamoto H, Haga N. Molecular targeting therapy of cancer: Drug resistance, apoptosis and survival signal. Cancer Sci. 2003;94(1):15-21.

  5. Donnenberg VS, Donnenberg AD. Multiple drug resistance in cancer revisited: The cancer stem cell hypothesis. J Clinical Pharmacol. 2005;45(8):872-7.

  6. Harris AL, Hochhauser D. Mechanisms of multidrug resistance in cancer treatment. Acta Oncol. 1992;31(2):205-13.

  7. Shabbits JA, Krishna R, Mayer LD. Molecular and pharmacological strategies to overcome multidrug resistance. Expert Rev Anticancer Ther. 2001;1(4):585-94.

  8. Li J, Bauer M, Moe B, Leslie E, Li X. Multidrug resistance protein 4 (MRP4/ABCC4) protects cells from the toxic effects of halobenzoquinones. Chem Res Toxicol. 2017;30(10):1815-22.

  9. Geisler M, Aryal B, di Donato M, Hao P. A critical view on ABC transporters and their interacting partners in auxin transport. Plant Cell Physiol. 2017;58(10):1601-14.

  10. Do T, Martinoia E, Lee Y. Functions of ABC transporters in plant growth and development. Curr Opin Plant Biol. 2017;41:32-8.

  11. Gupta PB, Chaffer CL, Weinberg RA. Cancer stem cells:Mirage or reality? NatMed. 2009;15(9):1010-2.

  12. Hu CM, Zhang L. Therapeutic nanoparticles to combat cancer drug resistance. Curr Drug Metab. 2009;10(8):836-41.

  13. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: Therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761-9.

  14. Hu C-MJ, Kaushal S, Cao HST, Aryal S, Sartor M, Esener S, Bouvet M, Zhang L. Half-antibody functionalized lipid-polymer hybrid nanoparticles for targeted drug delivery to carcinoembryonic antigen presenting pancreatic cancer cells. Mol Pharmaceut. 2010;7(3):914-20.

  15. Phil L, Naveed M, Mohammad IS, Bo L, Bin D. Chitooligosaccharide: An evaluation of physicochemical and biological properties with the proposition for determination of thermal degradation products. Biomed Pharmacother. 2018;102:438-51.

  16. Patil Y, Sadhukha T, Ma L, Panyam J. Nanoparticle-mediated simultaneous and targeted delivery of paclitaxel and tariquidar overcomes tumor drug resistance. J Control Release. 2009;136(1):21-9.

  17. Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers for overcoming drug resistance in cancer. Adv Drug Deliv Rev. 2002;54(5):759-79.

  18. Advani R, Fisher GA, Lum BL, Hausdorff J, Halsey J, Litchman M, Sikic BI. A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance. Clin Cancer Res. 2001;7(5):1221-9.

  19. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976;455(1):152-62.

  20. Kartner N, Riordan, Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science. 1983;221(4617):1285.

  21. Ueda K, Cardarelli C, Gottesman MM, Pastan I. Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci U S A. 1987;84(9):3004-8.

  22. Roger E, Kalscheuer S, Kirtane A, Guru BR, Grill AE, Whittum-Hudson J, Panyam J. Folic acid functionalized nanoparticles for enhanced oral drug delivery. Mol Pharmaceut. 2012;9(7):2103-10.

  23. Becker M, Levy D. Modeling the transfer of drug resistance in solid tumors. Bull Math Biol. 2017;79(10):2394-2412.

  24. Sauna ZE, Ambudkar SV. Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein. Proc Natl Acad Sci U S A. 2000;97(6):2515-20.

  25. Loo TW, Clarke DM. Do drug substrates enter the common drug-binding pocket of P-glycoprotein through "gates"? Biochem Biophys Res Commun. 2005;329(2):419-22.

  26. Mohammad IS, He W, Yin L. Understanding of human ATP binding cassette superfamily and novel multidrug resistance modulators to overcome MDR. Biomed Pharmacother. 2018;100:335-48.

  27. Sognier MA, Yin Z, Eberle RL, Sweet KM, Altenberg GA, Belli JA. Sequestration of doxorubicin in vesicles in a multidrug-resistant cell line (LZ-100). Biochem Pharmacol. 1994;48(2):391-401.

  28. Jeddi F, Soozangar N, Sadeghi M, Somi M, Shirmohamadi M, Eftekhar-Sadat A, Samadi N. Nrf2 over-expression is associated with P-glycoprotein upregulation in gastric cancer. Biomed Pharmacother. 2017;97:286-92.

  29. Bhosale RR, Gangadharappa HV, Gowda DV, Osmani RAMA, Vaghela R, Kulkarni PK, Sairam KV, Gurupadayya B. Current perspectives on novel drug carrier systems and therapies for management of pancreatic cancer: An updated inclusive review. Crit Rev Ther Drug Carrier Syst. 2018;35(3):195-292.

  30. Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. J Pharm Sci. 2006;5:219.

  31. Rooney PH, Stevenson DAJ, Marsh S, Johnston PG, Haites NE, Cassidy J, McLeod HL. Comparative genomic hybridization analysis of chromosomal alterations induced by the development of resistance to thymidylate synthase inhibitors. Cancer Res. 1998;58(22):5042-5.

  32. Abolhoda A, Wilson AE, Ross H, Danenberg PV, Burt M, Scotto KW. Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin Cancer Res. 1999;5(11):3352-6.

  33. Ambudkar SV, Sauna ZE, Gottesman MM, Szakacs G. A novel way to spread drug resistance in tumor cells: Functional intercellular transfer of P-glycoprotein (ABCB1). Trends Pharmacol Sci. 2005;26(8):385-7.

  34. Cornelison R, Llaneza D, Landen C. Emerging therapeutics to overcome chemoresistance in epithelial ovarian cancer: A mini-review. Int J Mol Sci. 2017;18(10):2171.

  35. Balendiran GK, Dabur R, Fraser D. The role of glutathione in cancer. Cell Biochem Funct. 2004;22(6):343-52.

  36. Townsend DM, Tew KD, He L, King JB, Hanigan MH. Role of glutathione S-transferase Pi in cisplatin-induced nephrotoxicity. Biomed Pharmacother. 2009;63(2):79-85.

  37. Martin LP, Hamilton TC, Schilder RJ. Platinum resistance: The role of DNA repair pathways. Clin Cancer Res. 2008;14(5):1291-5.

  38. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CHM, Jones DL, Visvader J, Weissman IL, Wahl GM. Cancer stem cells-perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 2006;66(19):9339-44.

  39. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer 2005;5(4):275-84.

  40. Cheng L, Zhang S, Davidson DD, Montironi R, Lopez-Beltran A. Implications of cancer stem cells for cancer therapy. In: Teicher BA, Bagley RG, editors. Stem cells and cancer. Totowa, NJ: Humana Press; 2009. p. 255-62.

  41. Abubaker K, Latifi A, Luwor R, Nazaretian S, Zhu H, Quinn MA, Thompson EW, Findlay JK, Ahmed N. Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden. Mol Cancer. 2013;12:24.

  42. Li L, Bhatia R. Stem cell quiescence. Clin Cancer Res. 2011;17(15):4936-41.

  43. Baldini N, Scotlandi K, Barbanti-Brodano G, Manara MC, Maurici D, Bacci G, Bertoni F, Picci P, Sottili S, Campanacci M, Serra M. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med. 1995;333(21):1380-5.

  44. Karaszi E, Jakab K, Homolya L, Szakacs G, Hollo Z, Telek B, Kiss A, Rejto L, Nahajevszky S, Sarkadi B, Kappelmayer J. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia. Br J Haematol. 2001;112(2):308-14.

  45. Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen I-M, Head DR, Appelbaum FR, Willman CL. Acute myeloid leukemia in the elderly: Assessment of multidrug resistance (mdr1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemo-therapy. a southwest oncology group study. Blood. 1997;89(9):3323-9.

  46. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646-74.

  47. Hameed A, Ijaz S, Mohammad IS, Muhammad KS, Akhtar N, Khan HMS. Aglycone solanidine and solasodine derivatives: A natural approach towards cancer. Biomed Pharmacother. 2017;94:446-57.

  48. Moll UM, Wolff S, Speidel D, Deppert W. Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol. 2005;17(6):631-6.

  49. Ajabnoor GMA, Crook T, Coley HM. Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells. Cell Death Dis. 2012;3:e260.

  50. Sakalar Q, Izgi K, Iskender B, Sezen S, Aksu H, Qakir M, Kurt B, Turan A, Canatan H. The combination of thymoquinone and paclitaxel shows anti-tumor activity through the interplay with apoptosis network in triple-negative breast cancer. Tumor Biol. 2016;37(4):4467-77.

  51. Hameed A, Ijaz S, Mohammad IS, Muhammad KS, Akhtar N, Khan HMS. Aglycone solanidine and solasodine derivatives: A natural approach towards cancer. Biomed Pharmacother. 2017;94:446-57.

  52. Pham T-A, Mohammad IS, Vu V-T, Hu X-L, Birendra C, Ulah A, Guo C, Lu X-Y, Ye W-C, Wang H. Phloroglucinol derivatives from the fruits of eucalyptus globulus and their cytotoxic activities. Chem Biodivers. 2018;15(6):e1800052.

  53. Tuo J, Xie Y, Song J, Chen Y, Guo Q, Liu X, Ni X, Xu D, Huang H, Yin S, Zhu W, Wu J, Hu H. Development of a novel berberine-mediated mitochondria-targeting nano-platform for drug-resistant cancer therapy. J Mater Chem B. 2016;4(42):6856-64.

  54. Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296(5573):1655.

  55. Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2002;2:420.

  56. Tschopp J, Martinon F, Hofmann K. Apoptosis: Silencing the death receptors. Curr Biol. 1999;9(10):381-4.

  57. Sinicrope FA, Rego RL, Okumura K, Foster NR, O'Connell MJ, Sargent DJ, Windschitl HE. Prognostic impact of bim, puma, and noxa expression in human colon carcinomas. Clin Cancer Res. 2008;14(18):5810-8.

  58. Lage H. An overview of cancer multidrug resistance: A still unsolved problem. Cell Mol Life Sci. 2008;65(20):3145.

  59. Bradbury PA, Middleton MR. DNA repair pathways in drug resistance in melanoma. Anticancer drugs. 2004;15(5):421-6.

  60. Li W, Melton DW. Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance. Oncogene. 2012;31(19):2412-22.

  61. Youn C-K, Kim M-H, Cho H-J, Kim H-B, Chang I-Y, Chung M-H, You HJ. Oncogenic H-Ras up-regulates expression of ERCC1 to protect cells from platinum-based anticancer agents. Cancer Res. 2004;64(14):4849-57.

  62. Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN. Loss of the mismatch repair protein msh6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res. 2007;13(7):2038-45.

  63. Britten RA. Modification of radiosensitivity following chemotherapy exposure: Potential implications for combined-modality therapy. In: Andersson B, Murray D, editors. Clinically relevant resistance in cancer chemotherapy. Boston: Springer; 2002. p. 285-303.

  64. Jain RK. Determinants of tumor blood flow: A review. Cancer Res. 1988;48(10):2641-58.

  65. Tredan O, Galmarini CM, Patel K, Tannock IF. Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst. 2007;99(19):1441-54.

  66. Cairns R, Papandreou I, Denko N. Overcoming physiologic barriers to cancer treatment by molecularly targeting the tumor microenvironment. Mol Cancer Res. 2006;4(2):61-70.

  67. Hirst DG, Denekamp J. Tumour cell proliferation in relation to the vasculature. Cell Tissue Kinet. 1979;12(1):31-42.

  68. Curti BD, Urba WJ, Gregory Alvord W, Janik JE, Smith JW, Madara K, Longo DL. Interstitial pressure of subcutaneous nodules in melanoma and lymphoma patients: Changes during treatment. Cancer Res. 1993;53(10):2204-7.

  69. Klionsky DJ. Look people, "Atg" is an abbreviation for "autophagy-related." That's it. Autophagy. 2012;8(9):1281-2.

  70. Li Y-J, Lei Y-H, Yao N, Wang C-R, Hu N, Ye W-C, Zhang D-M, Chen Z-S. Autophagy and multidrug resistance in cancer. Chin J Cancer. 2017;36(1):52.

  71. Brown CM, Reisfeld B, Mayeno AN. Cytochromes P450: A structure-based summary of biotransfor-mations using representative substrates. Drug Metab Rev. 2008;40(1):1-100.

  72. Purnapatre K, Khattar SK, Saini KS. Cytochrome P450s in the development of target-based anticancer drugs. Cancer Lett. 2008;259(1):1-15.

  73. Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-drug interactions. J Neuro immune Pharm. 2006;1(3):323-39.

  74. Iyanagi T. Molecular mechanism of phase I and phase II drug-metabolizing enzymes: Implications for detoxification. Int Rev Cytol. 2007;260:35-112.

  75. Ghezzi P. Protein glutathionylation in health and disease. Biochim BiophysActa. 2013;1830(5):3165-72.

  76. Hemmerich S, Verdugo D, Rath VL. Strategies for drug discovery by targeting sulfation pathways. Drug Discov Today. 2004;9(22):967-75.

  77. Deeley RG, Westlake C, Cole SPC. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev. 2006;86(3):849-99.

  78. Ekhart C, Rodenhuis S, Smits PHM, Beijnen JH, Huitema ADR. An overview of the relations between polymorphisms in drug metabolising enzymes and drug transporters and survival after cancer drug treatment. Cancer Treat Rev. 2009;35(1):18-31.

  79. Shen H, Liu T, Fu L, Zhao S, Fan B, Cao J, Li X. Identification of microRNAs involved in dexamethasone-induced muscle atrophy. Mol Cell Biochem. 2013;381(1):105-13.

  80. Bao L, Haque A, Jackson K, Hazari S, Moroz K, Jetly R, Dash S. Increased expression of P-Glycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model. American J Pathol. 2011;178(2):838-52.

  81. Huang Z, Zhang L, Zhu D, Shan X, Zhou X, Qi L-W, Wu L, Zhu J, Cheng W, Zhang H, Chen Y, Zhu W, Wang T, Liu P. A novel serum microRNA signature to screen esophageal squamous cell carcinoma. Cancer Med. 2017;6(1):109-19.

  82. Hong L, Han Y, Zhang H, Li M, Gong T, Sun L, Wu K, Zhao Q, Fan D. The prognostic and chemotherapeutic value of miR-296 in esophageal squamous cell carcinoma. Ann Surg. 2010;251(6):1056-63.

  83. Fu W, Pang L, Chen Y, Yang L, Zhu J, Wei Y. The microRNAs as prognostic biomarkers for survival in esophageal cancer: A meta-analysis. Sci World J. 2014;2014:8.

  84. Dong W-H, Li Q, Zhang X-Y, Guo Q, Li H, Wang T-Y. Deep sequencing identifies deregulation of microRNAs involved with vincristine drug-resistance of colon cancer cells. Int J Clin Exp Pathol. 2015;8(9):11524-30.

  85. Perez J, Bardin C, Rigal C, Anthony B, Rousseau R, Dutour A. Anti-MDRl siRNA restores chemosensitivity in chemoresistant breast carcinoma and osteosarcoma cell lines. Anticancer Res. 2011;31(9):2813-20.

  86. Fisher M, Abramov M, Van Aerschot A, Xu D, Juliano RL, Herdewijn P. Inhibition of MDR1 expression with altritol-modified siRNAs. Nucleic Acids Res. 2007;35(4):1064-74.

  87. Liu S, Wang H, Zhang L, Tang C, Jones L, Ye H, Ban L, Wang A, Liu Z, Lou F, Zhang D, Sun H, Dong H, Zhang G, Dong Z, Guo B, Yan H, Yan C, Wang L, Su Z, Li Y, Huang XF, Chen S-Y, Zhou T. Rapid detection of genetic mutations in individual breast cancer patients by next-generation DNA sequencing. Hum Genomics. 2015;9(1):2.

  88. Duan Z, Chen C, Qin J, Liu Q, Wang Q, Xu X, Wang J. Cell-penetrating peptide conjugates to enhance the antitumor effect of paclitaxel on drug-resistant lung cancer. Drug Deliv. 2017;24(1):752-64.

  89. Mechetner EB, Roninson IB. Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc Natl Acad Sci U S A. 1992;89(13):5824-8.

  90. Naito M, Tsuge H, Kuroko C, Koyama T, Tomida A, Tatsuta T, Heike Y, Tsuruo T. Enhancement of cellular accumulation of cyclosporine by anti-P-glycoprotein monoclonal antibody MRK-16 and synergistic modulation of multidrug resistance. J Natl Cancer Inst. 1993;85(4):311-6.

  91. Watanabe T, Tsuruo T, Naito M, Kokubu N. Regression of established tumors expressing P-glycoprotein by combinations of adriamycin, cyclosporin derivatives, and MRK-16 antibodies. J Natl Cancer Inst. 1997;89(7):512-8.

  92. Goda K, Fenyvesi F, Bacso Z, Nagy H, Marian T, Megyeri A, Krasznai Z, Juhasz I, Vecsernyes M, Szabo G. Complete inhibition of p-glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody. J Pharmacol Exp Therapeut. 2007;320(1):81-8.

  93. Thomas H, Coley HM. Overcoming multidrug resistance in cancer: An update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control. 2003;10(2):159.

  94. Su Y, Cheng X, Tan Y, Hu Y, Zhou Y, Liu J, Xu Y, Xie Y, Wang C, Gao Y, Wang J, Cheng T, Yang C, Xiong D, Miao H. Synthesis of a dual functional anti-MDR tumor agent PH II-7 with elucidations of anti-tumor effects and mechanisms. PLoS One. 2012;7(3):e32782.

  95. Dong X, Mumper R. Nanomedicinal strategies to treat multidrug-resistant tumors: Current progress. Nanomedicine (Lond). 2010;5(4):597-615.

  96. Beh CW, Seow WY, Wang Y, Zhang Y, Ong ZY, Ee PLR, Yang Y-Y. Efficient delivery of Bcl-2-targeted siRNA using cationic polymer nanoparticles: Downregulating mRNA expression level and sensitizing cancer cells to anticancer drug. Biomacromolecules. 2009;10(1):41-8.

  97. Chen AM, Zhang M, Wei D, Stueber D, Taratula O, Minko T, He H. Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug- resistant cancer cells. Small. 2009;5(23):2673-7.

  98. Cheng D, Cao N, Chen J, Yu X, Shuai X. Multifunctional nanocarrier mediated co-delivery of doxorubicin and siRNA for synergistic enhancement of glioma apoptosis in rat. Biomaterials. 2012;33(4):1170-9.

  99. Saad M, Garbuzenko OB, Minko T. Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer. Nanomedicine. 2008;3(6):761-76.

  100. Devalapally H, Duan Z, Seiden MV, Amiji MM. Modulation of drug resistance in ovarian adenocarcinoma by enhancing intracellular ceramide using tamoxifen-loaded biodegradable polymeric nanoparticles. Clin Cancer Res. 2008;14(10):3193.

  101. Deng W-G, Kawashima H, Wu G, Jayachandran G, Xu K, Minna JD, Roth JA, Ji L. Synergistic tumor suppression by coexpression of FUS1 and p53 is associated with down-regulation of murine double minute-2 and activation of the apoptotic protease-activating factor 1-dependent apoptotic pathway in human non-small cell lung cancer cells. Cancer Res. 2007;67(2):709.

  102. Choi SH, Jin S-E, Lee M-K, Lim S-J, Park J-S, Kim B-G, Ahn WS, Kim C-K. Novel cationic solid lipid nanoparticles enhanced p53 gene transfer to lung cancer cells. Eur J Pharm Biopharm. 2008;68(3):545-54.

  103. Xu L, Pirollo KF, Tang W-H, Rait A, Chang EH. Transferrin-liposome-mediated systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts. Hum Gene Ther. 1999;10(18):2941-52.

  104. Ueda K, Kawashima H, Ohtani S, Deng W-G, Ravoori M, Bankson J, Gao B, Girard L, Minna JD, Roth JA, Kundra V, Ji L. The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin- induced resistance in human non-small-cell lung cancer cells. Cancer Res. 2006;66(19):9682.

  105. Shuhendler AJ, Cheung RY, Manias J, Connor A, Rauth AM, Wu XY. A novel doxorubicin-mitomycin C co-encapsulated nanoparticle formulation exhibits anti-cancer synergy in multidrug resistant human breast cancer cells. Breast Cancer Res Treat. 2009;119(2):255.

  106. Cairns R, Papandreou I, Denko N. Overcoming physiologic barriers to cancer treatment by molecu- larly targeting the tumor microenvironment. Mol Cancer Res. 2006;4(2):61.

  107. Ambasta RK, Sharma A, Kumar P. Nanoparticle mediated targeting of VEGFR and cancer stem cells for cancer therapy. Vasc Cell. 2011;3(1):26.

  108. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinote- can, fluorouracil, and leucovorin for metastatic colorectal cancer. N Eng J Med. 2004;350(23):2335-42.

  109. Mei J, Gao Y, Zhang L, Cai X, Qian Z, Huang H, Huang W. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro. Exp Oncol. 2008;30(1):29-34.

  110. Lee SH, Kim SH, Park TG. Intracellular siRNA delivery system using polyelectrolyte complex micelles prepared from VEGF siRNA-PEG conjugate and cationic fusogenic peptide. Biochem Biophys Res Commun. 2007;357(2):511-6.

  111. Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. Local and systemic delivery of VEGF siRNA using polyelectrolyte complex micelles for effective treatment of cancer. J Control Release. 2008;129(2):107-16.

  112. Murata N, Takashima Y, Toyoshima K, Yamamoto M, Okada H. Anti-tumor effects of anti-VEGF siRNA encapsulated with PLGA microspheres in mice. J Control Release. 2008;126(3):246-54.

  113. Niola F, Evangelisti C, Campagnola L, Massalini S, Bue MC, Mangiola A, Masotti A, Maira G, Farace MG, Ciafre SA. A plasmid-encoded VEGF siRNA reduces glioblastoma angiogenesis and its combination with interleukin-4 blocks tumor growth in a xenograft mouse model. Cancer Biol Ther. 2006;5(2):174-9.

  114. Tailor TD, Hanna G, Yarmolenko PS, Dreher MR, Betof AS, Nixon AB, Spasojevic I, Dewhirst MW. Effect of pazopanib on tumor microenvironment and liposome delivery. Mol Cancer Ther. 2010;9(6):1798.

  115. Herringson TP, Altin JG. Effective tumor targeting and enhanced anti-tumor effect of liposomes engrafted with peptides specific for tumor lymphatics and vasculature. Int J Pharm. 2011;411(1-2):206-14.

  116. Nasongkla N, Shuai X, Ai H, Weinberg BD, Pink J, Boothman DA, Gao J. cRGD-functionalized polymer micelles for targeted doxorubicin delivery. Angew Chem Int Ed Engl. 2004;43(46):6323-7.

  117. Gomes-da-Silva LC, Santos AO, Bimbo LM, Moura V, Ramalho JS, Pedroso de Lima MC, Simoes S, Moreira JN. Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment. Int J Pharm. 2012;434(1):9-19.

  118. Abu Lila AS, Kizuki S, Doi Y, Suzuki T, Ishida T, Kiwada H. Oxaliplatin encapsulated in PEG-coated cationic liposomes induces significant tumor growth suppression via a dual-targeting approach in a murine solid tumor model. J Control Release. 2009;137(1):8-14.

  119. Zhiqiang Y, Changyou Z, Ziyi W, Linglin F, Fei W, Yu L, Xiangkun Y, Qing D, Min L, Weiyue L. LyP- 1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics. Nanotechnology. 2011;22(41):415103.

  120. Shapira A, Livney YD, Broxterman HJ, Assaraf YG. Nanomedicine for targeted cancer therapy: Towards the overcoming of drug resistance. Drug Resist Updat. 2011;14(3):150-63.

  121. Alama A, Orengo AM, Ferrini S, Gangemi R. Targeting cancer-initiating cell drug-resistance: A road-map to a new-generation of cancer therapies? Drug Discov Today. 2012;17(9-10):435-42.

  122. Lacerda L, Pusztai L, Woodward WA. The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches. Drug Resist Updat. 2010;13(4):99-108.

  123. Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S, Sarkar FH. Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance. Drug Resist Updat. 2010;13(4):109-18.

  124. Wang C-H, Chiou S-H, Chou C-P, Chen Y-C, Huang Y-J, Peng C-A. Photothermolysis of glioblastoma stem-like cells targeted by carbon nano tubes conjugated with CD133 monoclonal antibody. Nanomedicine. 2011;7(1):69-79.

  125. Yuan Y, Cai T, Xia X, Zhang R, Chiba P, Cai Y. Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer. Drug Deliv. 2016;23(9):3350-7.

  126. Bar-Zeev M, Assaraf YG, Livney YD. P-casein nanovehicles for oral delivery of chemotherapeutic drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells. Oncotarget. 2016;7(17):23322-34.

  127. Sun T, Zhang YS, Pang B, Hyun DC, Yang M, Xia Y. Engineered nanoparticles for drug delivery in cancer therapy. Angew Chem Int Ed Engl. 2014;53(46):12320-64.

  128. Yang L, Li W, Kirberger M, Liao W, Ren J. Design of nanomaterial based systems for novel vaccine development. Biomater Sci. 2016;4(5):785-802.

  129. Zhang TT, Li W, Meng G, Wang P, Liao W. Strategies for transporting nanoparticles across the blood-brain barrier. Biomater Sci. 2016;4(2):219-29.

  130. Zhang M, Akbulut M. Adsorption, desorption, and removal of polymeric nanomedicine on and from cellulose surfaces: Effect of size. Langmuir. 2011;27(20):12550-9.

  131. Li W. The era of nanotechnology and omics sciences. Eur J BioMed Res. 2017;1(1):2.

  132. Harsha S. Dual drug delivery system for targeting H. pylori in the stomach: Preparation and in vitro characterization of amoxicillin-loaded Carbopol nanospheres. Int J Nanomed. 2012;7:4787-96.

  133. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Eng J Med. 2013;369(18):1691-703.

  134. Dhar S, Gu FX, Langer R, Farokhzad OC, Lippard SJ. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles. Proc Natl Acad Sci U S A. 2008;105(45):17356-61.

  135. Gu L-Q, Cui P-F, Xing L, He Y-J, Chang X, Zhou T-J, Liu Y, Li L, Jiang H-L. An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance. RSC Advances. 2019;9(21):12110-23.

  136. Wang Q, Zou C, Wang L, Gao X, Wu J, Tan S, Wu G. Doxorubicin and adjudin co-loaded pH-sensitive nanoparticles for the treatment of drug-resistant cancer. Acta Biomater. 2019;94:469-81.

  137. Mishra V, Kesharwani P, Jain NK. Biomedical applications and toxicological aspects of functionalized carbon nanotubes. Crit Rev Ther Drug Carrier Syst. 2018;35(4):293-330.

  138. Yao HJ, Sun L, Liu Y, Jiang S, Pu Y, Li J, Zhang Y. Monodistearoyl- phosphatidylethanolamine-hyaluronic acid functionalization of single-walled carbon nanotubes for targeting intracellular drug delivery to overcome multidrug resistance of cancer cells. Carbon. 2016;96:362-76.

  139. Park JW. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Res. 2002;4(3): 95.

  140. Ogawara K-I, Un K, Tanaka K-I, Higaki K, Kimura T. In vivo anti-tumor effect of PEG liposomal doxorubicin (DOX) in DOX-resistant tumor-bearing mice: Involvement of cytotoxic effect on vascular endothelial cells. J Control Release. 2009;133(1):4-10.

  141. Assanhou A, Li W, Zhang L, Xue L, Kong L, Sun H, Mo R, Zhang C. Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment. Biomaterials. 2015;73:284-95.

  142. Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: Design, characterization and biological significance. Adv Drug Deliv Rev. 2001;47(1):113-31.

  143. Jin X, Zhou B, Xue L, San W. Soluplus(R) micelles as a potential drug delivery system for reversal of resistant tumor. Biomed Pharmacother. 2015;69:388-95.

  144. Sheng J, Li F, Wong STC. Optimal drug prediction from personal genomics profiles. IEEE J Biomed Health. 2015;19(4):1264-70.

  145. Guo D, Ji X, Peng F, Zhong Y, Chu B, Su Y, He Y. Photostable and biocompatible fluorescent silicon nanoparticles for imaging-guided co-delivery of siRNA and doxorubicin to drug-resistant cancer cells. Nano-Micro Lett. 2019;11(1):27.

  146. Wang H, Gao Z, Liu X, Agarwal P, Zhao S, Conroy DW, Ji G, Yu J, Jaroniec CP, Liu Z, Lu X, Li X, He X. Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance. Nat Commun. 2018;9(1):562.

  147. Yang L, Zhang X, Ye M, Jiang J, Yang R, Fu T, Chen Y, Wang K, Liu C, Tan W. Aptamer-conjugated nanomaterials and their applications. Adv Drug Deliv Rev. 2011;63(14):1361-70.

  148. Lee S-M, Kim HJ, Kim SY, Kwon M-K, Kim S, Cho A, Yun M, Shin J-S, Yoo K-H. Drug-loaded gold plasmonic nanoparticles for treatment of multidrug resistance in cancer. Biomaterials. 2014;35(7):2272-82.

  149. Luo C, Li Y, Guo L, Zhang F, Liu H, Zhang J, Zheng J, Zhang J, Guo S. Graphene quantum dots down-regulate multiple multidrug-resistant genes via interacting with their C-rich promoters. Adv Healthc Mater. 2017;6(21):1700328.

  150. Zhao L, Cheng Y, Hu J, Wu Q, Xu T. Host-guest chemistry of dendrimer-drug complexes. 3. competitive binding of multiple drugs by a single dendrimer for combination therapy. J Phys Chem B. 2009;113(43):14172-9.

  151. Tekade RK, Dutta T, Gajbhiye V, Jain NK. Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics. J Microencapsul. 2009;26(4):287-96.

  152. Nagpal K, Kumar P, Mohan A, Thakur S. Dendrimers for therapeutic delivery: Compositions, characterizations, and current status. Crit Rev Ther Drug Carrier Syst. 2019;36(4):277-304.

  153. Li Y, Zhang X, Zhang Z, Wu H, Xu X, Gu Z. Tumor-adapting and tumor-remodeling AuNR dendrimer-assembly nanohybrids overcome impermeable multidrug-resistant cancer. Mater Horiz. 2018;5(6):1047-57.

  154. Li J, Liang H, Liu J, Wang Z. Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy. Int J Pharm. 2018;546(1):215-25.

  155. Li J, Liu J, Guo N, Zhang X. Reversal of multidrug resistance in breast cancer MCF-7/ADR cells by h-R3-siMDR1-PAMAM complexes. Int J Pharm. 2016;511(1):436-45.

  156. Mignani S, Tripathi RP, Chen L, Caminade A-M, Shi X, Majoral J-P. New ways to treat tuberculosis using dendrimers as nanocarriers. Pharmaceutics. 2018;10(3):105.

  157. Khan I, Khan R, Asif H, Alamgeer N, Khalid S, Asghar S, Saleem M, Shah K, Shah S, Rizvi S, Shahzad Y. Co-delivery strategies to overcome multidrug resistance in ovarian cancer. Int J Pharm. 2017;533(1):111-24.

  158. Huwyler J, Cerletti A, Flicker G, Eberle AN, Drewe J. By-passing of P-glycoprotein using immunoliposomes. J Drug Target. 2002;10(1):73-9.

  159. Rejman J, Oberle V, Zuhorn IS, Hoekstra D. Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J. 2004;377(1):159.

  160. Emilienne Soma C, Dubernet C, Bentolila D, Benita S, Couvreur P. Reversion of multidrug resistance by co-encapsulation of doxorubicin and cyclosporin A in polyalkylcyanoacrylate nanoparticles. Biomaterials. 2000;21(1):1-7.

  161. Liang G-W, Lu W-L, Wu J-W, Zhao J-H, Hong H-Y, Long C, Li T, Zhang Y-T, Zhang H, Wang J-C, Zhang X, Zhang Q. Enhanced therapeutic effects on the multi-drug resistant human leukemia cells in vitro and xenograft in mice using the stealthy liposomal vincristine plus quinacrine. Fund Clin Pharmacol. 2008;22(4):429-37.

  162. Wu J, Lu Y, Lee A, Pan X, Yang X, Zhao X, Lee RJ. Reversal of multidrug resistance by transferrin-conjugated liposomes co-encapsulating doxorubicin and verapamil. J Pharm Pharm Sci. 2007;10(3):350-7.

  163. Ganta S, Amiji M. Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm. 2009;6(3):928-39.

  164. Cao X, Yu LX, Barbaciru C, Landowski CP, Shin H-C, Gibbs S, Miller HA, Amidon GL, Sun D. Permeability dominates in vivo intestinal absorption of P-gp substrate with high solubility and high permeability. Mol Pharm. 2005;2(4):329-40.

  165. Mohammad IS, He W, Yin L. A smart paclitaxel-disulfiram nanococrystals for efficient MDR reversal and enhanced apoptosis. Pharm Res. 2018;35(4):77.

  166. Mohammad IS, Teng C, Chaurasiya B, Yin L, Wu C, He W. Drug-delivering-drug approach-based codelivery of paclitaxel and disulfiram for treating multidrug-resistant cancer. Int J Pharm. 2019;557:304-13.

  167. Tang B, Qian Y, Gou Y, Cheng G, Fang G. VE-albumin core-shell nanoparticles for paclitaxel delivery to treat MDR breast cancer. Molecules. 2018;23(11):2760.

  168. van Vlerken LE, Duan Z, Little SR, Seiden MV, Amiji MM. Augmentation of therapeutic efficacy in drug-resistant tumor models using ceramide coadministration in temporal-controlled polymer-blend nanoparticle delivery systems. AAPS J. 2010;12(2):171-80.

  169. Patel NM, Nozaki S, Shortle NH, Bhat-Nakshatri P, Newton TR, Rice S, Gelfanov V, Boswell SH, Goulet RJ Jr, Sledge GW Jr, Nakshatri H. Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide. Oncogene. 2000;19(36):4159-69.

  170. Fan L, Li F, Zhang H, Wang Y, Cheng C, Li X, Gu C-H, Yang Q, Wu H, Zhang S. Co-delivery of PDTC and doxorubicin by multifunctional micellar nanoparticles to achieve active targeted drug delivery and overcome multidrug resistance. Biomaterials. 2010;31(21):5634-42.

  171. Misra R, Sahoo SK. Coformulation of Doxorubicin and curcumin in poly(d,l-lactide-co-glycolide) nanoparticles suppresses the development of multidrug resistance in K562 cells. Mol Pharm. 2011;8(3):852-66.

  172. Singh SK, Lillard JW, Singh R. Reversal of drug resistance by planetary ball milled (PBM) nanoparticle loaded with resveratrol and docetaxel in prostate cancer. Cancer Lett. 2018;427:49-62.

  173. Shin H-C, Alani AWG, Cho H, Bae Y, Kolesar JM, Kwon GS. A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs. Mol Pharm. 2011;8(4):1257-65.

  174. Aryal S, Hu C-MJ, Zhang L. Combinatorial drug conjugation enables nanoparticle dual-drug delivery. Small. 2010;6(13):1442-8.

  175. Kolishetti N, Dhar S, Valencia PM, Lin LQ, Karnik R, Lippard SJ, Langer R, Farokhzad OC. Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy. Proc Natl Acad Sci U S A. 2010;107(42):17939-44.

  176. Pavillard V, Kherfellah D, Richard S, Robert J, Montaudon D. Effects of the combination of camptothecin and doxorubicin or etoposide on rat glioma cells and camptothecin-resistant variants. Br J Cancer. 2001;85(7):1077-83.

  177. Raitanen M, Rantanen V, Kulmala J, Helenius H, Grenman R, Grenman S. Supra-additive effect with concurrent paclitaxel and cisplatin in vulvar squamous cell carcinoma in vitro. Int J Cancer. 2002;100(2):238-43.

  178. Feldman EJ, Lancet JE, Kolitz JE, Ritchie EK, Roboz GJ, List AF, Allen SL, Asatiani E, Mayer LD, Swenson C, Louie AC. First-in-man study of CPX-351: A liposomal carrier containing cytarabine and daunorubicin in a fixed 5:1 molar ratio for the treatment of relapsed and refractory acute myeloid leukemia. J Clin Oncol. 2011;29(8):979-85.

  179. Batist G, Gelmon KA, Chi KN, Miller WH, Chia SKL, Mayer LD, Swenson CE, Janoff AS, Louie AC. Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Clin Cancer Res. 2009;15(2):692.

  180. Aryal S, Hu C-MJ, Zhang L. Polymeric nanoparticles with precise ratiometric control over drug loading for combination therapy. Mol Pharm. 2011;8(4):1401-7.

  181. Bar-Zeev M, Livney Y, Assaraf Y. Targeted nanomedicine for cancer therapeutics: Towards precision medicine overcoming drug resistance. Drug Resist Updat. 2017;31:15-30.

  182. Navyatha B, Nara S. Theranostic nanostructures for ovarian cancer. Crit Rev Ther Drug Carrier Syst. 2019;36(4):305-71.

  183. Duan X, Xiao J, Yin Q, Zhang Z, Yu H, Mao S, Li Y. Smart pH-sensitive and temporal-controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram. ACS Nano. 2013;7(7):5858-69.

  184. Sengupta S, Eavarone D, Capila I, Zhao G, Watson N, Kiziltepe T, Sasisekharan R. Temporal targeting oftumour cells and neovasculature with a nanoscale delivery system. Nature. 2005;436(7050):568-72.

  185. Wang Z, Ho PC. A nanocapsular combinatorial sequential drug delivery system for antiangiogenesis and anticancer activities. Biomaterials. 2010;31(27):7115-23.

  186. Shah MA, Schwartz GK. Cell cycle-mediated drug resistance. Clin Cancer Res. 2001;7(8):2168.

  187. Singh MS, Tammam SN, Shetab Boushehri MA, Lamprecht A. MDR in cancer: Addressing the underlying cellular alterations with the use of nanocarriers. Pharmacol Res. 2017;126:2-30.

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