Poly(β-cyclodextrin)/platinum prodrug supramolecular nano system for enhanced cancer therapy: Synthesis and in vivo
Ruhe Zhang1, Xinru You2, Moucheng Luo1
1School of Biomedical Engineering; State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou 510006, China.
Abstract:
The use of cisplatin is restricted by systemic toxicity and drug resistance. Supramolecular nano-drug delivery systems involving drugs as building blocks circumvent these limitations promisingly. Herein, we describe a novel supramolecular system [Pt(IV)-SSNPs] based on poly(β-cyclodextrin), which was synthesized for efficient loading of adamantly-functionalized platinum(IV) prodrug [Pt(IV)-ADA2] via the host-guest interaction between β-cyclodextrin and adamantyl. Pt(IV)-ADA2 can be converted to active cisplatin in reducing environment in cancer cells, which further reduces systemic toxicity. The introduction of the adamantane group-tethered mPEG2k endowed the Pt(IV)-SSNPs with a longer blood circulation time. In vitro assays exhibited that the Pt(IV)-SSNPs could be uptaken by CT26 cells, resulting in cell cycle arrest in the G2/M and S phases, together with apoptosis. Furthermore, the Pt(IV)-SSNPs showed effective tumor accumulation, better antitumor effect, and negligible cytotoxicity to major organs. These results indicate that supramolecular nanoparticles are a promising platform for efficient cisplatin delivery and cancer treatment.
