Abstract
To reduce the problems of poor solubility, high in vivo dosage requirement, and weak targeting ability of paclitaxel (PTX), a hyaluronic acid-octadecylamine (HA-ODA)-modified nano-structured lipid carrier (HA-NLC) was constructed. HA-ODA conjugates were synthesized by an amide reaction between HA and ODA. The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC. The HA-NLC displayed strong internalization in cluster determinant 44 (CD44) highly expressed MCF-7 cells, and endocytosis mediated by the CD44 receptor was involved. The HA-NLC had an encapsulation efficiency of PTX of 72.0%. The cytotoxicity of the PTX-loaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol®. In vivo, the HA-NLC exhibited strong tumor targeting ability. The distribution of the NLCs to the liver and spleen was reduced after HA modification, while more nanoparticles were aggregated to the tumor site. Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.
概要
目 的
以脂质纳米载体为递药系统向肿瘤部位靶向输送难溶性抗肿瘤药物紫杉醇, 实现药物的靶向递送.
创新点
采用一端疏水化的透明质酸修饰脂质纳米载体, 利用透明质酸与肿瘤部位高表达 CD44 的特异性结合, 实现载药脂质纳米粒的靶向输送.
方 法
通过酰胺反应, 将硬脂胺化学嫁接至透明质酸, 制备透明质酸-硬脂胺嫁接物. 采用水性溶剂扩散法制备脂质纳米粒, 并将透明质酸-硬脂胺嫁接物插入脂质纳米粒的表面. 使用红外染料 DiR 标记脂质纳米粒, 通过小动物活体成像技术观察标记脂质纳米粒的体内分布.
结 论
透明质酸修饰的脂质纳米粒, 可通过与 CD44 的特异性结合, 实现抗肿瘤药物的靶向递送.
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Xiao LIU performed the experimental research, analyzed the data, and wrote the manuscript. Hai LIU contributed to the study design and data analysis. Su-lan WANG performed the establishment of animal models. Jing-wen LIU wrote and edited the manuscript. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Xiao LIU, Hai LIU, Su-lan WANG, and Jing-wen LIU declare that they have no conflict of interest.
All the animal studies were conducted according to the guidelines issued by the Ethical Committee of Zhejiang University, Hangzhou, China (Ethical Approval No. 14481) and all animal experiments complied with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978).
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Project supported by the Zhejiang Provincial Natural Science Foundation of China (No. LY14H160016)
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Liu, X., Liu, H., Wang, Sl. et al. Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy. J. Zhejiang Univ. Sci. B 21, 571–580 (2020). https://doi.org/10.1631/jzus.B1900624
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DOI: https://doi.org/10.1631/jzus.B1900624
Key words
- Paclitaxel (PTX)
- Hyaluronic acid-octadecylamine (HA-ODA)
- Nano-structured lipid carrier (NLC)
- Tumor targeting
- In vivo distribution