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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.

透明质酸衍生物修饰脂质纳米载体的抗肿瘤作用及体内靶向研究

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[29]List of electronic supplementary materials

[30]Fig. S1 Zeta potential determination of the nanoparticles (NLC, NLC/PTX, HA-NLC, and HA-NLC/PTX)

[31]Fig. S2 Size distribution of the nanoparticles (NLC, NLC/PTX, HA-NLC, and HA-NLC/PTX) at the 10th day after they were prepared