Polymer-Caged Nanobins for Synergistic Cisplatin−Doxorubicin Combination Chemotherapy
- 15 November 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 132 (48), 17130-17138
- https://doi.org/10.1021/ja107333g
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-PCNDXR 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.Keywords
This publication has 48 references indexed in Scilit:
- Biological Evaluation of pH-Responsive Polymer-Caged Nanobins for Breast Cancer TherapyACS Nano, 2010
- Coencapsulation of Arsenic‐ and Platinum‐based Drugs for Targeted Cancer TreatmentAngewandte Chemie International Edition, 2009
- “Clickable” Polymer-Caged Nanobins as a Modular Drug Delivery PlatformJournal of the American Chemical Society, 2009
- Targeting DNA topoisomerase II in cancer chemotherapyNature Reviews Cancer, 2009
- Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA–PEG nanoparticlesProceedings of the National Academy of Sciences, 2008
- The resurgence of platinum-based cancer chemotherapyNature Reviews Cancer, 2007
- Soluble Single-Walled Carbon Nanotubes as Longboat Delivery Systems for Platinum(IV) Anticancer Drug DesignJournal of the American Chemical Society, 2007
- Second-line chemotherapy with pegylated liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO phase II trialAnnals of Oncology, 2006
- Targeting multidrug resistance in cancerNature Reviews Drug Discovery, 2006
- Cellular processing of platinum anticancer drugsNature Reviews Drug Discovery, 2005