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

Abstract

Camptothecin (CPT) is a potent chemotherapeutic drug for colorectal cancer (CRC), however, its clinical use is impeded by low solubility, non‐tumor‐targeting ability, and has fast blood clearance. The self‐assembly of hydrophobic drugs into discrete nanostructures, especially nanoparticles (NPs), can improve their anti‐cancer effects. However, it is difficult to form stable nano‐assemblies using free CPT. In this study, arginine‐glycine‐aspartic acid (RGD), a hydrophilic and tumor‐targeting peptide, was conjugated with CPT through a glutathione‐cleavable disulfide bond to form an amphiphile conjugate CPT‐ss‐RGD. Simultaneously, a conjugate without redox‐responsive ability (CPT‐cc‐RGD) was used as a control. Both CPT‐ss‐RGD and CPT‐cc‐RGD self‐assembled into stable NPs in an aqueous solution with diameters of approximately 86 and 70 nm, respectively. They exhibited low critical aggregation concentrations and good stability. More importantly, CPT‐ss‐RGD NPs showed a glutathione‐responsive drug release behavior. They can be specifically taken up by CRC SW480 and CT26 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.This article is protected by copyright. All rights reserved