Self‐assembled Amphiphilic Camptothecin Nanoparticles with Glutathione‐Responsive and Tumor‐Targeting Ability for Enhanced Colorectal Cancer Therapy

Abstract Camptothecin (CPT) is impeded by low solubility, non‐tumor‐targeting ability, and fast blood clearance. Self‐assembly of hydrophobic drugs into nanostructures, especially nanoparticles (NPs), can improve their anti‐cancer effects. In this study, arginine‐glycine‐aspartic acid (RGD), a hydrophilic and tumor‐targeting peptide, is conjugated with CPT through a glutathione‐cleavable disulfide bond. The synthesized amphiphilic molecule CPT‐ss‐RGD self‐assembled into stable NPs in an aqueous solution with diameters of ≈86nm. They exhibited low critical aggregation concentrations, good stability, and glutathione responsiveness. They can be specifically taken up by CRC cells through RGD integrin‐mediated uptake, and exhibit high toxicity to CRC cells and multicellular tumor spheroids. As expected, CPT‐ss‐RGD NPs prolonged the blood circulation time and enhanced the tumor accumulation of CPT, exhibiting excellent anti‐tumor growth ability and few side effects. Thus, CPT‐ss‐RGD NPs have great clinical translational potential for CRC therapy. The successful self‐assembly of the CPT‐ss‐RGD NPs provides a new method for the self‐delivery of hydrophobic therapeutics in vivo.