Hyaluronic Acid Oligosaccharide-Modified Zeolitic Imidazolate Framework-8 Nanoparticles Loaded with Oxaliplatin as A Targeted Drug-Delivery System for Colorectal Cancer Therapy

Abstract

Aim: Exploring a nanoscale targeted drug-delivery system (DDS) for oxaliplatin (Oxa) to improve its therapeutic effect in colorectal cancer. Materials & methods: Nanoparticles were prepared using zeolitic imidazole framework-8 (ZIF-8) modified by hyaluronic acid oligosaccharide (oHA) as an Oxa carrier (oHA@ZIF-8@Oxa). After multiple characterizations, the therapeutic efficacy of the DDS was evaluated by cytotoxicity testing and a nude mouse tumor transplantation experiment in vivo. Results: The results of characterization showed the DDS was homogeneous in morphology and uniform in dispersion. The drug loading of Oxa was 11.82% and the encapsulation efficiency was 90.8%. The cytotoxicity test and in vivo experiments showed that oHA@ZIF-8@Oxa had a more significant anticolorectal cancer effect than free Oxa. Conclusion: This work offers a promising potential DDS for enhancing the anticolorectal cancer effect of Oxa.

Current Advances of Nanomaterial-Based Oral Drug Delivery for Colorectal Cancer Treatment

“…HA is currently the best drug delivery vehicle for intestinal diseases due to its ability to specifically bind to the receptor CD44, its transmucosal action, and its protective effect against injured mucosa. Li et al [84] successfully synthesized a pH-responsive nano-DDS targeting the oHA receptor, oHA@ZIF-8@Oxa, thus improving the efficacy of Oxa against CRC. The oHA can compete for the binding of endogenous HA to CD44 by inhibiting the MDR and other ABC transporter protein expression, breaking the "HA-CD44" barrier in vivo, reversing the chemotherapy resistance of tumors, and penetrating the colonic mucosa more potently to play a role.…”