Orlistat-Dopamine Conjugate Micelles Improve Targeted Delivery and Therapeutic Efficiency of Camptothecin in Combination Chemotherapy

Abstract

Conventional chemotherapy as monotherapy comes with the problem of drug resistance in cancer, a high risk of severe side effects, and low drug delivery efficiency. Recently, we reported an orlistat-dopamine conjugate (ODC) with highly improved cytotoxicity against drug resistant cancers. Here, the orlistat-dopamine conjugate micelles (ODCM) were fabricated as a facile nanocarrier for camptothecin (CPT) to achieve combination therapy with highly therapeutic efficacy and selectivity against multi-drug resistant cancers. Due to the inherent bio-adhesive properties of the catechol moieties presented in ODCMs, CPT-ODCMs exhibited rapid accumulation on the cell membrane and facilitated efficient endocytosis by cancer cells. Followed by a two-stage continuous process to kill cancer cells, CPT-ODCM efficiently inhibited the proliferation of different cancer cells under hypoxia. The CPT-ODCM assembles different agents to become more effective and selective in chemotherapy through synergistic mechanism and provides a novel approach for combination therapy.