Polymer-Caged Nanobins for Synergistic Cisplatin−Doxorubicin Combination Chemotherapy

摘要

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.