Orlistat–dopamine conjugate micelles improve targeted delivery and therapeutic efficiency of camptothecin in combination chemotherapy

Abstract

Conventional chemotherapy as a monotherapy often suffers from drug resistance, severe systemic toxicity, and limited delivery efficiency. To address these limitations, we developed orlistat–dopamine conjugate micelles (ODCMs) as a dual-functional nanocarrier for camptothecin (CPT), enabling synergistic combination therapy against multidrug-resistant cancers. Owing to the bio-adhesive properties of the catechol moieties present in ODCMs, CPT-ODCMs rapidly accumulated at the cancer cell membrane and facilitated efficient cellular uptake. The system exhibited pH-responsive, two-stage drug release-initiating reactive oxygen species (ROS) generation and monoamine oxidase (MAO)-mediated cytotoxicity, followed by CPT-induced apoptosis, resulting in enhanced antitumor efficacy under hypoxic conditions. This platform assembles different agents to become more effective and selective in chemotherapy through a synergistic mechanism and offers a promising strategy for overcoming drug resistance in cancer therapy.