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Non-small cell lung cancer targeted nanoparticles with reduced side effects fabricated by flash nanoprecipitation

Mingwei Wang,Haiyan Huang,Zilong Zhong,Xinyue Chen,Yuan Fang,Shenxin Chen,Zhiyao Qi,Dan-rong Yang,Junyou Wang,Wei Bian

Published 2023 in Cancer nanotechnology

ABSTRACT

Background Tyrosine kinase inhibitors (TKI) have been highlighted for the therapy of non-small-cell lung cancer (NSCLC), due to their capability of efficiently blocking signal pathway of epidermal growth factor receptor (EGFR) which causes the inhibition and apoptosis of NSCLC cells. However, EGFR-TKIs have poor aqueous solubility and severe side effects arising from the difficulty in control of biodistribution. In this study, folate-functionalized nanoparticles (FA-NPs) are designed and fabricated to load EGFR-TKI through flash nanoprecipitation (FNP) strategy, which could enhance the tumor-targeting drug delivery and reduced drug accumulation and side effects to normal tissues. Results Herein, the EGFR-TKI loaded FA-NPs are constructed by FNP, with FA decorated dextran- b -polylactide as polymeric stabilizer and gefitinib as TKI. The fast mixing and co-precipitation in FNP provide FA-NPs with well-defined particle size, narrow size distribution and high drug loading content. The FA-NPs exhibit efficient uptake and cytotoxicity in HCC827 NSCLC cells, and reduced uptake and cytotoxicity in normal cells comparing with free gefitinib. In vivo evaluation of gefitinib-loaded FA-NPs confirms the selective drug delivery and accumulation, leading to enhanced inhibition on NSCLC tumor and simultaneously diminished side effects to normal tissues. Conclusion The facile design of FA-NPs by FNP and their achieved performance in vitro and in vivo evaluations offer new therapeutic opportunities for treatment of non-small cell lung cancer. Graphical Abstract

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