Decorating Delivery Vehicles Using Hyaluronic Acid Oligosaccharides Enables Active Targeting Toward Cancer and Minimizes Adverse Effect of Chemotherapeutics

Author:

Jia Weibin12,Li Runrun1,Zou Fengjuan1,Li Min1,Weng Hongjuan1,Shen Qianqian1,Qi Guozhen1,Zhou Ruipiao1,Shi Yikang1,Gu Guofeng1,Wang Fengshan13,Chen Zonggang1ORCID

Affiliation:

1. National Glycoengineering Research Center and Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate‐based Medicine Shandong University Qingdao 266237 China

2. Hong Kong Centre for Cerebro‐Cardiovascular Health Engineering Hong Kong Science Park Hong Kong SAR 999077 China

3. School of Pharmaceutical Sciences Shandong University Jinan 250012 China

Abstract

AbstractThe major drawback of conventional chemotherapeutic treatment is the non‐specificity or inability to ascertain and target cancerous cells directly. In this study, an active targeting strategy that is poised to carry the anticancer agents to the desired sites for therapeutic action while avoiding toxicity to normal organs is provided. The active targeting of delivery vehicles is achieved by ligand‐receptor interactions, in particular the specific binding between hyaluronic acid oligosaccharides (oHAs) and CD44 receptors. This study first prepares oHAs by the size‐exclusion chromatography and utilizes them to decorate chitosan (CTS) as basic materials (oHAs‐CTS) for drug delivery, then fabricates oHAs‐CTS into micro/nanoscale carriers to encapsulate agents for cancer chemotherapy. The oHAs‐CTS micro/nanocarriers exhibit high drug encapsulation efficiency (58–87%), and the drug releases present a sustained behavior. Notably, oHAs‐CTS delivery vehicles display an enhanced active targeting toward cancers and alleviate the cytotoxic effects on normal cells. Additionally, in vivo results show that drug‐laden oHAs‐CTS nanocarriers demonstrate a significant inhibitory effect on 4 T1 tumors without any toxicity to the major organs. Taken together, the findings highlight the potential of oHAs‐CTS micro/nanospheres as delivery vehicles with enhanced active targeted capability toward cancers and minimized adverse effects of chemotherapeutic agents for cancer treatment.

Publisher

Wiley

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