Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance

Autor: Xue Han, Ruijuan Su, Xiuqing Huang, Yingli Wang, Xiao Kuang, Shuang Zhou, Hongzhuo Liu
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Asian Journal of Pharmaceutical Sciences, Vol 14, Iss 5, Pp 569-580 (2019)
Druh dokumentu: article
ISSN: 1818-0876
DOI: 10.1016/j.ajps.2018.06.006
Popis: Mitochondria are currently known as novel targets for treating cancer, especially for tumors displaying multidrug resistance (MDR). This present study aimed to develop a mitochondria-targeted delivery system by using triphenylphosphonium cation (TPP+)-conjugated Brij 98 as the functional stabilizer to modify paclitaxel (PTX) nanocrystals (NCs) against drug-resistant cancer cells. Evaluations were performed on 2D monolayer and 3D multicellular spheroids (MCs) of MCF-7 cells and MCF-7/ADR cells. In comparison with free PTX and the non-targeted PTX NCs, the targeted PTX NCs showed the strongest cytotoxicity against both 2D MCF-7 and MCF-7/ADR cells, which was correlated with decreased mitochondrial membrane potential. The targeted PTX NCs exhibited deeper penetration on MCF-7 MCs and more significant growth inhibition on both MCF-7 and MCF-7/ADR MCs. The proposed strategy indicated that the TPP+-modified NCs represent a potentially viable approach for targeted chemotherapeutic molecules to mitochondria. This strategy might provide promising therapeutic outcomes to overcome MDR. Keywords: Paclitaxel, Nanocrystals, Brij 98, Triphenylphosphonium, Multidrug resistance, Mitochondria
Databáze: Directory of Open Access Journals