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

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.