Cancer cell membrane biomimetic composites of cisplatin prodrug for targeted eradication of circulating tumor cells in whole blood

Abstract

The dissemination of circulating tumor cells in the peripheral blood circulation system plays a fundamental role in cancer recurrence and metastasis. Therefore, it is a pivotal scientific requirement to eradicate circulating tumor cells in whole blood system effectively. In this work, we provide a pH and GSH responsive drug delivery and release composites using cancer cell membrane biomimetic nanoparticles loaded with Pt(IV) prodrug (CM-Pt(IV) NPs), which exhibits high selectivity and biocompatibility. Cancer cells tend to form homogeneous aggregates by interacting with tumor-specific binding proteins on their surface. Thus, the cancer cell membrane coating possesses a homologous targeting ability to circulating tumor cells. The core nano-carrier composites loaded with Platinum(IV) agents were prepared by combining PLGA, Hyaluronic acid, and Cystamine. Within the nano-carrier composites, the S–S bond was reduced to S–H due to the high concentration of GSH present in cancer cells under an environment with a pH of 6.8. Consequently, this facilitates the release of platinum drugs that can specifically bind to cell DNA and effectively eradicate cancer cells. This highly selective delivery and precise release composites enable CM-Pt(IV) NPs to eliminate circulating tumor cells in the peripheral blood system effectively. This study provides an efficient drug delivery strategy for treating metastatic cancer.