Advertisement

Journal of Pharmaceutical Investigation

, Volume 46, Issue 4, pp 325–339 | Cite as

Nanoparticle-based combination drug delivery systems for synergistic cancer treatment

  • Ju Yeon Choi
  • Raj Kumar Thapa
  • Chul Soon Yong
  • Jong Oh Kim
Review

Abstract

Despite being a leading cause of death worldwide, cancer remains difficult to treat due to the development of drug resistance and severe adverse effects associated with conventional chemotherapy. Hence, combination chemotherapy is theoretically advantageous owing to the synergistic effects of drugs and suppression of drug resistance. Nanoparticle-mediated chemotherapeutic delivery is a promising approach for the effective treatment of various cancers because it may simultaneously enhance therapeutic effects and reduce side effects. The loading of multiple chemotherapeutic agents to these systems could additionally improve the antineoplastic efficacy. This review highlights recent advances in combination chemotherapy using small-molecule chemotherapeutic agents via nanocarrier systems, e.g., liposomes, polymeric micelles, dendrimers, polymer-drug conjugates, and mesoporous silica nanoparticles. Specifically, it emphasizes the unique properties of these systems that make them amenable to optimized treatments with respect to efficacy and safety and clarifies areas in which current therapeutic strategies can be improved.

Keywords

Nanoparticle Combination chemotherapy Synergistic effect Nanocarrier 

Notes

Acknowledgments

This research was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. 2015R1A2A2A01004118, 2015R1A2A2A04004806).

Conflict of interest

The authors have no conflict of interest.

References

  1. Agrawal V, Paul MK, Mukhopadhyay AK (2005) 6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization. J Liposome Res 15(3–4):141–155PubMedCrossRefGoogle Scholar
  2. Al-Jamal WT, Kostarelos K (2011) Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine. Acc Chem Res 44(10):1094–1104PubMedCrossRefGoogle Scholar
  3. Arcos D, López-Noriega A, Ruiz-Hernández E, Terasaki O, Vallet-Regi M (2009) Ordered mesoporous microspheres for bone grafting and gene delivery. Chem Mater 21(6):1000–1009CrossRefGoogle Scholar
  4. Armstrong AJ, Carducci MA (2006) New drugs in prostate cancer. Curr Opin Urol 16(3):138–145PubMedCrossRefGoogle Scholar
  5. Bae Y, Diezi TA, Zhao A, Kwon GS (2007) Mixed polymeric micelles for combination cancer chemotherapy through the concurrent delivery of multiple chemotherapeutic agents. J Control Release 122:324–330PubMedCrossRefGoogle Scholar
  6. Bae Y, Alani AW, Rockich NC, Lai TS, Kwon GS (2010) Mixed pH-sensitive polymeric micelles for combination drug delivery. Pharm Res 27(11):2421–2432PubMedCrossRefGoogle Scholar
  7. Baeza A, Colilla M, Vallet-Regi M (2015) Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery. Expert Opin Drug Deliv 12(2):319–337PubMedCrossRefGoogle Scholar
  8. Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13(1):238–252PubMedCrossRefGoogle Scholar
  9. Batist G, Gelmon KA, Chi KN, Miller WH Jr, Chia SK, Mayer LD, Swenson CE, Janoff AS, Louie AC (2009) Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Clin Cancer Res 15(2):692–700PubMedCrossRefGoogle Scholar
  10. Beer TM, Ryan C, Alumkal J, Ryan CW, Sun J, Eilers KM (2010) A phase II study of paclitaxel poliglumex in combination with transdermal estradiol for the treatment of metastatic castration-resistant prostate cancer after docetaxel chemotherapy. Anticancer Drugs 21(4):433–438PubMedCrossRefGoogle Scholar
  11. Bell A (2005) Antimalarial drug synergism and antagonism: mechanistic and clinical significance. FEMS Microbiol Lett 253(2):171–184PubMedCrossRefGoogle Scholar
  12. Boissiere C, Grosso D, Chaumonnot A, Nicole Sanchez C (2011) Aerosol route to functional nanostructured inorganic and hybrid porous materials. Adv Mater 23(5):599–623PubMedCrossRefGoogle Scholar
  13. Cai L, Xu G, Shi C, Guo D, Wang X, Luo J (2015) Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: a synergistic combination nanotherapy for ovarian cancer treatment. Biomaterials 37:456–468PubMedCrossRefGoogle Scholar
  14. Chipman SD, Oldham FB, Pezzoni G, Singer JW (2006) Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int J Nanomedicine 1(4):375–383PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chitkara D, Singh S, Kumar V, Danguah M, Behrman SW, Kumar N, Mahato RI (2012) Micellar delivery of cyclopamine and gefitinib for treating pancreatic cancer. Mol Pharm 9(8):2350–2357PubMedGoogle Scholar
  16. Cho H, Lai TC, Kwon GS (2013) Poly (ethylene glycol)-block-poly(epsilon-caprolactone) micelles for combination drug delivery: evaluation of paclitaxel, cyclopamine and gossypol in intraperitoneal xenograft models of ovarian cancer. J Control Release 166:1–9PubMedCrossRefGoogle Scholar
  17. Chou TC (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58(3):621–681PubMedCrossRefGoogle Scholar
  18. Chou TC (2010) Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 70(2):440–446PubMedCrossRefGoogle Scholar
  19. Colilla M, Manzano M, Izquierdo-Barba I, Vallet-Regi M, Boissiere C, Sanchez C (2010) Advanced drug delivery vectors with tailored surface properties made of mesoporous binary oxides submicronic spheres. Chem Mater 22(5):1821–1830CrossRefGoogle Scholar
  20. Croy SR, Kwon GS (2006) Polymeric micelles for drug delivery. Curr Pharm Des 12:4669–4684PubMedCrossRefGoogle Scholar
  21. De La Taille A, Vacherot F, Salomon L, Druel C, De Gil Diez Medina S, Abbou C, Buttyan R, Chopin D (2001) Hormone-refractory prostate cancer: a multi-step and multi-event process. Prostate Cancer Prostatic Dis 4(4):204–212CrossRefGoogle Scholar
  22. Delbaldo C, Michiels S, Syz N, Soria JC, Le Chevalier T, Pignon JP (2004) Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA 292(4):470–484PubMedCrossRefGoogle Scholar
  23. Desale SS, Cohen SM, Zhao Y, Kabanov AV, Bronich TK (2013) Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer. J Control Release 171(3):339–348PubMedPubMedCentralCrossRefGoogle Scholar
  24. Di Maio M, Chiodini P, Georgoulias V, Hatzidaki D, Takeda K, Wachters FM, Gebbia V, Smit EF, Morabito A, Gallo C, Perrone F, Gridelli C (2009) Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 27(11):1836–1843PubMedCrossRefGoogle Scholar
  25. Dilnawaz F, Singh A, Mohanty C, Sahoo SK (2010) Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 31(13):3694–3706PubMedCrossRefGoogle Scholar
  26. Dong JT (2006) Prevalent mutations in prostate cancer. J Cell Biochem 97(3):433–447PubMedCrossRefGoogle Scholar
  27. Duncan R (2006) Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer 6:688–701PubMedCrossRefGoogle Scholar
  28. Duncan R, Vicent MJ, Greco F, Nicholson RI (2005) Polymer-drug conjugates: towards a novel approach for the treatment of endocrine-related cancer. Endocr Relat Cancer 12:S189–S199PubMedCrossRefGoogle Scholar
  29. Fang J, Nakamura H, Marda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63(3):136–151PubMedCrossRefGoogle Scholar
  30. Ganta S, Amiji M (2009) Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm 6(3):928–939PubMedCrossRefGoogle Scholar
  31. Gao M, Xu Y, Qiu L (2015) Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes. Int J Nanomedicine 10:6615–6632PubMedPubMedCentralGoogle Scholar
  32. Greco F, Vicent MJ (2008) Polymer-drug conjugates: current status and future trends. Front Biosci 13:2744–2756PubMedCrossRefGoogle Scholar
  33. Greco F, Vicent MJ (2009) Combination therapy: opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines. Adv Drug Deliver Rev 61:1203–1213CrossRefGoogle Scholar
  34. Greco F, Vicent MJ, Gee S, Jones AT, Gee J, Nicholson RI, Duncan R (2007) Investigating the mechanism of enhanced cytotoxicity of HPMA copolymer-Dox-AGM in breast cancer cells. J Control Release 117(1):28–39PubMedCrossRefGoogle Scholar
  35. Grün M, Lauer I, Unger KK (1997) The synthesis of micrometer- and submicrometer-size spheres of ordered mesoporous oxide MCM-41. Adv Mater 9:254–257CrossRefGoogle Scholar
  36. Gustafson TP, Cao Q, Wang ST, Berezin MY (2013) Design of irreversible optical nanothermometers for thermal ablations. Chem Commun (Camb) 49(7):680–682CrossRefGoogle Scholar
  37. Han Y, He Z, Schulz A, Bronich TK, Jordan R, Luxenhofer R, Kabanov AV (2012) Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles. Mol Pharm 9(8):2302–2313PubMedPubMedCentralGoogle Scholar
  38. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70PubMedCrossRefGoogle Scholar
  39. Harasym TO, Tardi PG, Harasym NL, Harvie P, Johnstone SA, Mayer LD (2007) Increased preclinical efficacy of irinotecan and floxuridine coencapsulated inside liposomes is associated with tumor delivery of synergistic drug ratios. Oncol Res 16(8):361–374PubMedGoogle Scholar
  40. Hasenstein JR, Shin HC, Kasmerchak K, Buehler D, Kwon GS, Kozak KR (2012) Antitumor activity of Triolimus: a novel multidrug-loaded micelle containing paclitaxel, rapamycin, and 17-AAG. Mol Cancer Ther 11:2233–2242PubMedPubMedCentralCrossRefGoogle Scholar
  41. Hoffmann F, Cornelius M, Morell J, Fröba M (2006) Silica-based mesoporous organic-inorganic hybrid materials. Angew Chem Int Ed Engl 45(20):3216–3251PubMedCrossRefGoogle Scholar
  42. Hurley LH (2002) DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer 2:188–200PubMedCrossRefGoogle Scholar
  43. Ismael GF, Rosa DD, Mano MS, Awada A (2008) Novel cytotoxic drugs: old challenges, new solutions. Cancer Treat Rev 34(1):81–91PubMedCrossRefGoogle Scholar
  44. Jia J, Zhu F, Ma X, Cao Z, Li Y, Chen YZ (2009) Mechanism of drug combinations: interaction and network perspectives. Nat Rev Drug Discov 8(2):111–128PubMedCrossRefGoogle Scholar
  45. Johnson SM, Bangham AD, Hill MW, Korn ED (1971) Single bilayer liposomes. Biochim Biophys Acta 233(3):820–826PubMedCrossRefGoogle Scholar
  46. Kaneshiro TL, Lu ZR (2009) Targeted intracellular codelivery of chemotherapeutics and nucleic acid with a well-defined dendrimer-based nanoglobular carrier. Biomaterials 30(29):5660–5666PubMedCrossRefGoogle Scholar
  47. Katragadda U, Teng Q, Rayaprolu BM, Chandran T, Tan C (2011) Multi-drug delivery to tumor cells via micellar nanocarriers. Int J Pharm 419(1–2):281–286PubMedPubMedCentralCrossRefGoogle Scholar
  48. Kim S, Shi Y, Kim JY, Park K, Cheng JX (2010) Overcoming the barriers in micellar drug delivery: loading efficiency, in vivo stability, and micelle-cell interaction. Expert Opin Drug Deliv 7:49–62PubMedCrossRefGoogle Scholar
  49. Kitano H (2007) A robustness-based approach to systems-oriented drug design. Nat Rev Drug Discov 6(3):202–210PubMedCrossRefGoogle Scholar
  50. Kopecek J, Kopecková P (2010) HPMA copolymers: origins, early developments, present, and future. Adv Drug Deliv Rev 62(2):122–149PubMedCrossRefGoogle Scholar
  51. Krakovicová H, Etrych T, Ulbrich K (2009) HPMA-based polymer conjugates with drug combination. Eur J Pharm Sci 37(3–4):405–412PubMedCrossRefGoogle Scholar
  52. Lammers T, Subr V, Ulbrich K, Peschke P, Huber PE, Hennink WE, Storm G (2009) Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers. Biomaterials 30(20):3466–3475PubMedCrossRefGoogle Scholar
  53. Lasic DD (1998) Novel applications of liposomes. Trends Biotechnol 16(7):307–321PubMedCrossRefGoogle Scholar
  54. Lee KS, Chung HC, Im SA, Park YH, Kim CS, Kim SB, Rha SY, Lee MY, Ro J (2008) 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):241–250PubMedCrossRefGoogle Scholar
  55. Lee SM, O’Halloran TV, Nguyen ST (2010) Polymer-caged nanobins for synergistic cisplatin-doxorubicin combination chemotherapy. J Am Chem Soc 132(48):17130–17138PubMedCrossRefGoogle Scholar
  56. Li L, Liu T, Fu C, Liu H, Tan L, Meng X (2014a) Multifunctional silica-based nanocomposites for cancer nanotheranostics. J Biomed Nanotechnol 10(9):1784–1809PubMedCrossRefGoogle Scholar
  57. Li M, Tang Z, Lv S, Song W, Hong H, Jing X, Zhang Y, Chen X (2014b) Cisplatin crosslinked pH-sensitive nanoparticles for efficient delivery of doxorubicin. Biomaterials 35(12):3851–3864PubMedCrossRefGoogle Scholar
  58. Li XY, Zhao Y, Sun MG, Shi JF, Ju RJ, Zhang CX, Li XT, Zhao WY, Mu LM, Zeng F, Lou JN, Lu WL (2014c) Multifunctional liposomes loaded with paclitaxel and artemether for treatment of invasive brain glioma. Biomaterials 35(21):5591–5604PubMedCrossRefGoogle Scholar
  59. Ma X, Zhao Y, Ng KW, Zhao Y (2013) Integrated hollow mesoporous silica nanoparticles for target drug/siRNA co-delivery. Chemistry 19(46):15593–15603PubMedCrossRefGoogle Scholar
  60. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1–2):271–284PubMedCrossRefGoogle Scholar
  61. Martinez A, Fuentes-Paniagua E, Baeza A, Sánchez-Nieves J, Cicuendez M, Gómez R, de la Mata FJ, González B, Vallet-Regi M (2015) Mesoporous silica nanoparticles decorated with carbosilane dendrons as new non-viral oligonucleotide. Chemistry 21(44):15651–15666PubMedCrossRefGoogle Scholar
  62. Matsumura Y (2014) The drug discovery by nanomedicine and its clinical experience. Jpn J Clin Oncol 44:515–525PubMedCrossRefGoogle Scholar
  63. Matsumura Y, Kataoka K (2009) Preclinical and clinical studies of anti-cancer agent-incorporating polymer micelles. Cancer Sci 100:572–579PubMedCrossRefGoogle Scholar
  64. Mayer LD, Janoff AS (2007) Optimizing combination chemotherapy by controlling drug ratios. Mol Interv 7(4):216–223PubMedCrossRefGoogle Scholar
  65. Meng H, Wang M, Liu H, Liu X, Situ A, Wu B, Ji Z, Chang CH, Nel AE (2015) Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano 9(4):3540–3557PubMedPubMedCentralCrossRefGoogle Scholar
  66. Mills EJ, Thorlund K, Ioannidis JP (2012) Calculating additive treatment effects from multiple randomized trials provides useful estimates of combination therapies. J Clin Epidemiol 65(12):1282–1288PubMedCrossRefGoogle Scholar
  67. Minko T, Kopecková P, Kopecek J (2000) Efficacy of the chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma. Int J Cancer 86(1):108–117PubMedCrossRefGoogle Scholar
  68. Mita M, Mita A, Sarantopoulos J, Takimoto CH, Rowinsky EK, Romero O, Angiuli P, Allievi C, Eisenfeld A, Verschraegen CF (2009) Phase I study of paclitaxel poliglumex administered weekly for patients with advanced solid malignancies. Cancer Chemother Pharmacol 64(2):287–295PubMedCrossRefGoogle Scholar
  69. Miyata K, Christie RJ, Kataoka K (2011) Polymeric micelles for nanoscale drug delivery. React Funct Polym 71:227–234CrossRefGoogle Scholar
  70. Morton SW, Lee MJ, Deng ZJ, Dreaden EC, Siouve E, Shopsowitz KE, Shah NJ, Yaffe MB, Hammond PT (2014) A nanoparticle-based combination chemotherapy delivery system for enhanced tumor killing by dynamic rewiring of signaling pathways. Sci Signal 7(325):ra44PubMedPubMedCentralCrossRefGoogle Scholar
  71. Muhammad F, Guo M, Wang A, Zhao J, Qi W, Guo Y, Zhu G (2014) Responsive delivery of drug cocktail via mesoporous silica nanolamps. J Colloid Interface Sci 434:1–8PubMedCrossRefGoogle Scholar
  72. Muthu MS, Feng SS (2010) Nanopharmacology of liposomes developed for cancer therapy. Nanomedicine (Lond) 5(7):1017–1019CrossRefGoogle Scholar
  73. Na HS, Lim YK, Jeong YI, Lee HS, Lim YJ, Kang MS, Cho CS, Lee HC (2010) Combination antitumor effects of micelle-loaded anticancer drugs in a CT-26 murine colorectal carcinoma model. Int J Pharm 383(1–2):192–200PubMedCrossRefGoogle Scholar
  74. O’Brien ME, Socinski MA, Popovich AY, Bondarenko IN, Tomova A, Bilynsky BT, Hotko YS, Ganul VL, Kostinsky IY, Eisenfeld AJ, Sandalic L, Oldham FB, Bandstra B, Sandler AB, Singer JW (2008) J Thorac Oncol 3(7):728–734PubMedCrossRefGoogle Scholar
  75. Olson F, Hunt CA, Szoka FC, Vail WJ, Papahadjopoulos D (1979) Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. Biochim Biophys Acta 557(1):9–23PubMedCrossRefGoogle Scholar
  76. Pradhan R, Ramasamy T, Choi JY, Kim JH, Poudel BK, Tak JW, Nukolova N, Choi HG, Yong CS, Kim JO (2015) Hyaluronic acid-decorated poly (lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin. Carbohydr Polym 123:313–323PubMedCrossRefGoogle Scholar
  77. Putnam D, Kopecek J (1995) Polymer conjugates with anticancer activity. Adv Polym Sci 122:55–123CrossRefGoogle Scholar
  78. Ramasamy T, Haider ZS, Tran TH, Choi JY, Jeong JH, Shin BS, Choi HG, Yong CS, Kim JO (2014a) Layer-by-layer assembly of liposomal nanoparticles with PEGylated polyelectrolytes enhances systemic delivery of multiple anticancer drugs. Acta Biomater 10(12):5116–5127PubMedCrossRefGoogle Scholar
  79. Ramasamy T, Kim J, Choi HG, Yong CS, Kim JO (2014b) Novel dual drug-loaded block ionomer complex micelles for enhancing the efficacy of chemotherapy treatments. J Biomed Nanotechnol 10(7):1304–1312PubMedCrossRefGoogle Scholar
  80. Ramasamy T, Kim JH, Choi JY, Tran TH, Choi HG, Yong CS, Kim JO (2014c) pH sensitive polyelectrolyte complex micelles for highly effective combination chemotherapy. J Mater Chem B 2:6324–6333CrossRefGoogle Scholar
  81. Ramsay EC, Dos Santos N, Dragowska WH, Laskin JJ, Bally MB (2005) The formulation of lipid-based nanotechnologies for the delivery of fixed dose anticancer drug combinations. Curr Drug Deliv 2(4):341–351PubMedCrossRefGoogle Scholar
  82. Rapoport N (2007) Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery. Prog Polym Sci 32:962–990CrossRefGoogle Scholar
  83. Robertson JD, Orrenius S, Zhivotovsky B (2000) Review: nuclear events in apoptosis. J Struct Biol 129(2–3):346–358PubMedCrossRefGoogle Scholar
  84. Sabbatini P, Sill MW, O’Malley D, Adler L, Secord AA (2008) A phase II trial of paclitaxel poliglumex in recurrent or persistent ovarian or primary peritoneal cancer (EOC): a Gynecologic Oncology Group Study. Gynecol Oncol 111(3):455–460PubMedCrossRefGoogle Scholar
  85. Sapra P, Zhao H, Mehlig M, Malaby J, Kraft P, Longley C, Greenberger LM, Horak ID (2008) Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model. Clin Cancer Res 14(6):1888–1896PubMedCrossRefGoogle Scholar
  86. Scarano W, de Souza P, Stenzel MH (2015) Dual-drug delivery of curcumin and platinum drugs in polymeric micelles enhances the synergistic effects: a double act for the treatment of multi-drug-resistant cancer. Biomater Sci 3(1):163–174PubMedCrossRefGoogle Scholar
  87. Shim G, Lee S, Choi J, Lee S, Kim CW, Oh YK (2014) Liposomal co-delivery of omacetaxine mepesuccinate and doxorubicin for synergistic potentiation of antitumor activity. Pharm Res 31(8):2178–2185PubMedCrossRefGoogle Scholar
  88. Shin HC, Alani AW, Cho H, Bae Y, Kolesar JM, Kwon GS (2011) A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs. Mol Pharm 8:1257–1265PubMedPubMedCentralCrossRefGoogle Scholar
  89. Shin HC, Cho H, Lai TC, Kozak KR, Kolesar JM, Kwon GS (2012) Pharmacokinetic study of 3-in-1 poly (ethylene glycol)-block-poly (D, L-lactic acid) micelles carrying paclitaxel, 17-allylamino-17-demethoxygeldanamycin, and rapamycin. J Control Release 163:93–99PubMedPubMedCentralCrossRefGoogle Scholar
  90. Suggitt M, Bibby MC (2005) 50 years of preclinical anticancer drug screening: empirical to target-driven approaches. Clin Cancer Res 11(3):971–981PubMedGoogle Scholar
  91. Tacar O, Sriamornsak P, Dass CR (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65(2):157–170PubMedCrossRefGoogle Scholar
  92. Takakura Y, Hashida M (1995) Macromolecular drug carrier systems in cancer chemotherapy: macromolecular prodrugs. Crit Rev Oncol Hematol 18(3):207–231PubMedCrossRefGoogle Scholar
  93. Tardi P, Johnstone S, Harasym N, Xie S, Harasym T, Zisman N, Harvie P, Bermudes D, Mayer L (2009a) In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy. Leuk Res 33(1):129–139PubMedCrossRefGoogle Scholar
  94. Tardi PG, Dos Santos N, Harasym TO, Johnstone SA, Zisman N, Tsang AW, Bermudes DG, Mayer LD (2009b) Drug ratio-dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo. Mol Cancer Ther 8(8):2266–2275PubMedCrossRefGoogle Scholar
  95. Tekade RK, Dutta T, Gajbhiye V, Jain NK (2009) Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics. J Microencapsul 26(4):287–296PubMedCrossRefGoogle Scholar
  96. Thapa RK, Youn YS, Jeong JH, Choi HG, Yong CS, Kim JO (2016) Graphene oxide-wrapped PEGylated liquid crystalline nanoparticles for effective chemo-photothermal therapy of metastatic prostate cancer cells. Colloids Surf B Biointerfaces 143:271–277PubMedCrossRefGoogle Scholar
  97. Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4(2):145–160PubMedCrossRefGoogle Scholar
  98. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2012) Global cancer statistics. CA Cancer J Clin 65(2):87–108CrossRefGoogle Scholar
  99. Touma SE, Goldberg JS, Moench P, Guo X, Tickoo SK, Gudas LJ, Nanus DM (2005) Retionic acid and the histone deacetylase inhibitor trichostatin a inhibit the proliferation of human renal cell carcinoma in a xenograft tumor model. Clin Cancer Res 11(9):3558–3566PubMedCrossRefGoogle Scholar
  100. Tran TH, Nguyen HT, Pham TT, Choi JY, Choi HG, Yong CS, Kim JO (2015) Development of a graphene oxide nanocarrier for dual-drug chemo-phototherapy to overcome drug resistance in cancer. ACS Appl Mater Interfaces 7(51):28647–28655PubMedCrossRefGoogle Scholar
  101. Trewyn BG, Slowing II, Giri S, Chen HT, Lin VS (2007) Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol-gel process and applications in controlled release. Acc Chem Res 40(9):846–853PubMedCrossRefGoogle Scholar
  102. Vallet-Regí M, Colilla M, González B (2011) Medical applications of organic-inorganic hybrid materials within the field of silica-based bioceramics. Chem Soc Rev 40(2):596–607PubMedCrossRefGoogle Scholar
  103. Wang H, Zhao Y, Wu Y, Hu YL, Nan K, Nie G, Chen H (2011) Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials 32(32):8281–8290PubMedCrossRefGoogle Scholar
  104. Wang E, Xiong H, Zou D, Xie Z, Huang Y, Jing X, Sun X (2014) Co-delivery of oxaliplatin and demethylcantharidin via a polymer-drug conjugate. Macromol Biosci 14(4):588–596PubMedCrossRefGoogle Scholar
  105. Wang B, Yu XC, Xu SF, Xu M (2015) Paclitaxel and etoposide co-loaded polymeric nanoparticles for the effective combination therapy against human osteosarcoma. J Nanobiotechnol 13:22CrossRefGoogle Scholar
  106. Wong MY, Chiu GN (2010) Simultaneous liposomal delivery of quercetin and vincristine for enhanced estrogen-receptor-negative breast cancer treatment. Anticancer Drugs 21(4):401–410PubMedCrossRefGoogle Scholar
  107. Xiao B, Han MK, Viennois E, Wang L, Zhang M, Si X, Merlin D (2015) Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy. Nanoscale 7(42):17745–17755PubMedCrossRefGoogle Scholar
  108. Zhang L, Radovic-Moreno AF, Alexis F, Gu FX, Basto PA, Bagalkot V, Jon S, Langer RS, Farokhzad OC (2007) Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle-aptamer bioconjugates. ChemMedChem 2(9):1268–1271PubMedCrossRefGoogle Scholar
  109. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC (2008) Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther 83(5):761–769PubMedCrossRefGoogle Scholar
  110. Zhang X, Li J, Yan M (2016) Targeted hepatocellular carcinoma therapy: transferrin modified, self-assembled polymeric nanomedicine for co-delivery of cisplatin and doxorubicin. Drug Dev Ind Pharm. doi: 10.3109/03639045.2016.1160103 Google Scholar
  111. Zhong J, Li L, Zhu X, Guan S, Yang Q, Zhou Z, Zhang Z, Huang Y (2015) A smart polymeric platform for multistage nucleus-targeted anticancer drug delivery. Biomaterials 65:43–55PubMedCrossRefGoogle Scholar
  112. Zhu J, Xu X, Hu M, Qiu L (2015) Co-encapsulation of combretastatin-A4 phosphate and doxorubicin in polymerosomes for synergistic therapy of nasopharyngeal epidermal carcinoma. J Biomed Nanotechnol 11(6):997–1006PubMedCrossRefGoogle Scholar
  113. Zoli W, Ricotti L, Tesei A, Barzanti F, Amadori D (2001) In vitro preclinical models for a rational design of chemotherapy combinations in human tumors. Crit Rev Oncol Hematol 37(1):69–82PubMedCrossRefGoogle Scholar
  114. Zucker D, Barenholz Y (2010) Optimization of vincristine-topotecan combination—paving the way for improved chemotherapy regimens by nanoliposomes. J Control Release 146(3):326–333PubMedCrossRefGoogle Scholar
  115. Zucker D, Andriyanov AV, Steiner A, Raviv U, Barenholz Y (2012) Characterization of PEGylated nanoliposomes co-remotedly loaded with topotecan and vincristine: relating structure and pharmacokinetics to therapeutic efficacy. J Control Release 160(2):281–289PubMedCrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2016

Authors and Affiliations

  1. 1.College of PharmacyYeungnam UniversityGyeongsanSouth Korea

Personalised recommendations