Hybrid Nanoparticles Modified by Hyaluronic Acid Loading an HSP90 Inhibitor as a Novel Delivery System for Subcutaneous and Orthotopic Colon Cancer Therapy

• Published in: International journal of nanomedicine Vol. 16; pp. 1743 - 1755
• Main Authors: Pan, Chenwei, Zhang, Tiaotiao, Li, Shaoxun, Xu, Zhihua, Pan, Binhui, Xu, Sheng, Jin, Shuanghong, Lu, Guangrong, Yang, Shouxing, Xue, Zhanxiong, Chen, Ping, Shen, Xian, Wang, Fangyan, Xu, Changlong
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Benzoquinones - pharmacology; Biocompatible Materials - chemistry; Cancer; Cancer therapies; Care and treatment; cationic hybrid nanoparticles; Cell Line, Tumor; Chemotherapy; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Colorectal cancer; Drug Delivery Systems; Drugs; Efficiency; Endocytosis - drug effects; Experiments; Fatty Acids, Monounsaturated - chemistry; Flow cytometry; Fluorescence; Health aspects; Heat shock proteins; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; hsp90 inhibitor; Humans; Hyaluronan Receptors - metabolism; Hyaluronic acid; hyaluronic acid (ha); Hyaluronic Acid - chemistry; Inflammation; Lactams, Macrocyclic - pharmacology; Ligands; Lipids; Medical research; Mice; Microscopy; Morphology; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Original Research; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Polymers; Proteins; Quaternary Ammonium Compounds - chemistry; Subcutaneous Tissue - drug effects; Subcutaneous Tissue - pathology; targeted delivery system; China; targeted delivery system; HA; HSP90 inhibitor; cationic hybrid nanoparticles; colon cancer; hyaluronic acid
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S275805

As a therapeutic target for cancer treatment, HSP90 has been explored extensively. However, the significant side effects of the HSP90 inhibitor 17AAG have limited its clinical use. In this study, we used hyaluronic acid (HA)-decorated DOTAP-PLGA hybrid nanoparticles (HA-DOTAP-PLGA NPs) as 17AAG-delivery carriers for targeted colon cancer therapy. Different methods were used to characterize the successful fabrication of these hybrid PLGA NPs. Our results demonstrated that internalization of HA-NPs in colon cancer cells was governed by CD44receptor-mediated endocytosis. Annexin V-propidium iodide staining experiments revealed that cell apoptosis induced by HA-NPs-17AAG in colon cancer cells was more efficient than free 17AAG. In two animal models used to screen anticancer efficacy (Luc-HT29 subcutaneous xenograft and AOM/DSS-induced orthotopic tumor model), HA-NPs-17AAG significantly inhibited xenograft and orthotopic tumor growth, demonstrating HA-NPs-17AAG had much better therapeutic efficiency than free 17AAG. It is worth noting that great biocompatibility of HA-DOTAP-PLGA NPs was observed both in vitro and in vivo. Our research offers a preclinical proof of concept for colon cancer therapy with DOTAP-PLGA NPs as a creative drug-delivery system.