Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex

卵磷脂-壳聚糖纳米粒子负载紫杉醇-胆固醇复合物改善姑息性肿瘤内注射治疗的抗肿瘤效果

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作者:Xiao-Yang Chu, Wei Huang, Yu-Li Wang, Ling-Wei Meng, Li-Qing Chen, Ming-Ji Jin, Lu Chen, Chun-Hong Gao, Cheng Ge, Zhong-Gao Gao, Chun-Sheng Gao

Background

Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status.

Conclusion

In general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy.

Methods

In this study, a solvent-injection method was used to prepare paclitaxel-cholesterol complex-loaded lecithin-chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized.

Results

The particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration.

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