title: Polymer-caged nanobins for synergistic cisplatin-doxorubicin combination chemotherapy.
abstract: Multicomponent chemotherapy has increasingly become a strategy of great importance in clinical cancer treatments. However, this type of chemotherapy has not been demonstrated in nanoscale delivery vehicles where two cytotoxic agents can be packaged together, potentially leading to synergistic drug activities. Herein, we present the codelivery of doxorubicin and cisplatin via a single polymer-caged nanobin (PCN) and show that copackaging can yield strong synergy in the efficacy of these agents. Such a PCN comprises a doxorubicin-encapsulated liposomal core protected by a pH-responsive cisplatin prodrug-loaded polymer shell with tunable drug ratios and surface charge potentials. This dual-agent Pt-PCN(DXR) formulation dramatically enhances the overall cytotoxicity of each drug against cancer cells at reduced doses and exhibits higher synergy than combinations of either the free drugs or separately nano-packaged drugs. These results clearly indicate that the polymer-caged nanobin platform can offer new means for building synergy into combination chemotherapy regimens.
authors.affiliation: Department of Chemistry and the Center of Cancer Nanotechnology Excellence, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Thomas V
authors.initials: TV
authors.lastname: O'Halloran
authors.forename: SonBinh T
authors.initials: ST
authors.lastname: Nguyen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002214:Capsules; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004705:Endocytosis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D010984:Platinum / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D004337:Drug Carriers; D008055:Lipids; D011108:Polymers; D010984:Platinum; D004317:Doxorubicin; D002945:Cisplatin