A dual‐stimuli responsive supramolecular nanovector anchoring folic acid ligands for targeted delivery of anti‐colorectal drug hydroxycamptothecin

Abstract

Hydroxycamptothecin (HCPT) is a first-line anti-colorectal cancer chemotherapeutic agent. Nevertheless, the poor tumor-specific delivery properties of HCPT make it indiscriminate in killing normal and cancer cells, as well as impossible to achieve sustained treatment due to its low cumulative concentration in cancer cells. Here, a pH and temperature co-responsive supramolecular nanocarrier anchoring with folic acid (FA) ligands, termed PEHA-β-CD-FA/SDS NPs, was prepared based on electrostatic interaction between cationic mono-(6-pentaethylenehexamine)-β-CD (PEHA-β-CD-FA) and anionic sodium dodecyl sulfate (SDS). PEHA-β-CD-FA/SDS NPs exhibited assembly/disassembly behavior accompanied by co-regulation of temperature and pH and are therefore employed as nanocarriers to load, deliver, and release HCPT. Notably, the release rate of HCPT achieved 93.6% at pH = 8.5 and T = 45 C which simulates the microenvironment of colon cancer cells. Cell biology experiments demonstrated that the more precise targeting ability of HCPT-loaded NPs resulted in higher cytotoxicity to tumor cells but also less toxicity to normal cells BEAS-2B. Flow cytometry apoptosis analysis also demonstrated that HCPT-loaded NPs had a significant growth-inhibitory effect on SW480 colon cancer cells. We expected that the supramolecular nanoparticles combining active and passive targeting capabilities could be further developed as potential drug carrier formulations for enhancing the clinical efficacy of anti-colon cancer drugs.