Hydroxychloroquine loaded hollow apoferritin nanocages for cancer drug repurposing and autophagy inhibition.

Autor: Fang X; Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China., Zeng J; Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China., Li Y; Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China., Yu H; Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China., Wu Z; Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zhenghongwu66@cpu.edu.cn., Qi X; Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China; Hangzhou Innovative Institute of Pharmaceutics, China Pharmaceutical University, Hangzhou 310018, China. Electronic address: qixiaole523@cpu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Oct; Vol. 203, pp. 114473. Date of Electronic Publication: 2024 Aug 24.
DOI: 10.1016/j.ejpb.2024.114473
Abstrakt: Hydroxychloroquine sulfate (HCQ) is currently being repurposed for cancer treatment. The antitumor mechanism of HCQ is inhibition of cellular autophagy, but its therapeutic potential is severely limited by poor solubility, lack of tumor targeting and lower cellular uptake. Therefore, utilization of human H-chain apoferritin (HFn) composed only of heavy subunits is an attractive approach for tumor targeting drug delivery. This study focused on pH-triggered encapsulation of HCQ within the inner cavity of HFn to form HFn@HCQ nanoparticles for tumor-targeted drug delivery. Characterization using a range of techniques has been used to confirm the successful establishment of HFn@HCQ. HFn@HCQ exhibited pH-responsive release behavior, with almost no drug release at pH 7.4, but 80% release at pH 5.0. Owing to its intrinsic binding to transferrin receptor 1 (TfR1), HFn@HCQ was significantly internalized through TfR1-mediated endocytosis, with a 4.4-fold difference of internalization amount across cell lines. Additionally, HFn@HCQ enhanced the antitumor effect against four different cancer cell lines when compared against HCQ alone, especially in TfR1 high-expressing cells, where the inhibitory effect was 3-fold higher than free HCQ. The autophagy inhibition of HFn@HCQ has been demonstrated, which is a major pathway to induce cancer cell death. According to current findings, HFn based drug delivery is a promising strategy to target and kill TfR1 overexpressing tumor cells.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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