Novel hyaluronic acid oligosaccharide-loaded and CD44v6-targeting oxaliplatin nanoparticles for the treatment of colorectal cancer. (1st January 2021)

• Record Type: Journal Article
• Authors: Du, Wenlong; Yang, Xiaoping; He, Shenfu; Wang, Jia; Guo, Yuanxian; Kou, Bangguo; Jiang, Yongjie; Bian, Pan; Li, Bingtai; Yin, Lanning
• Is Part Of: Drug delivery. Volume 28:Number 1(2021)
• Page Start: 920
• Page End: 929
• Publication Date: 2021-01-01
• Subjects: Hyaluronic acid oligosaccharide -- CD44v6 -- oxaliplatin -- drug delivery system -- colorectal cancer; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.1080/10717544.2021.1914777
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: Oxaliplatin resistance is one of the main causes of failed colorectal cancer treatment, followed by recurrence and metastasis. In this study, we found that colorectal cancer cells secrete a high level of hyaluronic acid (HA), which interacts with its receptor CD44v6 to mediate colorectal cancer resistance to chemotherapy. HA oligosaccharide (oHA) is a degradation product of HA. We found that it competitively binds to CD44v6, reversing the HA–CD44v6-mediated effect of HA on oxaliplatin resistance. In addition, oHA showed no toxicity or immunogenicity but exhibited good biocompatibility and tumor-targeting capability. Therefore, we synthesized oHA-loaded oxaliplatin liposome nanoparticles (oHA-Lipid-Oxa) using a thin-film hydration method. The cytotoxicity of oHA-Lipid-Oxa was assessed in vitro using flow cytometry, which revealed greater lethality than oxaliplatin alone. Finally, we established a tumor-bearing nude mouse model and separately injected oHA-Lipid-Oxa, Lipid-Oxa, Oxa, oHA, and phosphate-buffered saline (PBS) into the tail vein to observe the antitumor effects of nanoparticles in vivo. The oHA-Lipid-Oxa group exhibited the highest tumor suppression rate, but the weight loss was not obvious. Hematoxylin and eosin staining showed greatest lymphocyte and macrophage infiltration in the oHA-Lipid-Oxa group. Moreover, oHA-Lipid-Oxa induced tumor cell apoptosis and necrosis most robustly compared with the other groups. We showed that oHA-Lipid-Oxa has excellent histocompatibility and CD44v6-targeting capabilities, thus greatly increasing the sensitivity to oxaliplatin and reducing adverse reactions. Accordingly, oHA-Lipid-Oxa has a broad potential for therapeutic application.