In vitro evaluation of mitochondrial-targeted taxol TPP-PEG-PE nanomicelles and promotion of tumor cell apoptosis / 中草药

ABSTRACT

Objective To prepare taxol TPP-PEG-PE nanomicelles and study its in vitro release behavior, mitochondrial targeting and pro-apoptosis of A549 lung cancer cells. Methods The taxol TPP-PEG-PE nanomicelles were prepared by membrane hydration method. Based on the drug loading, encapsulation efficiency and particle size, the preparation parameters of taxol TPP-PEG-PE nanomicelles were optimized. The preferred nano-drug delivery system was then characterized. The drug delivery system was evaluated by in vitro drug release, mitochondrial targeting, lung cancer cell toxicity, and apoptosis assay. Results The diameter of taxol TPP-PEG-PE nanomicelles was (18.7 ± 0.8) nm, Zeta potential was (13.4 ± 0.5) mV, and the results of TEM electron microscopy showed that the taxol TPP-PEG-PE nanomicelles were regular spheres of uniform size. Mitochondrial targeting experiments showed that TPP-PEG-PE nanomicelles can promote drug accumulation in mitochondrial sites. Lung cancer cytotoxicity assay showed that taxol TPP-PEG-PE nanomicelles had good anti-apoptotic effect, and Hoechst staining suggested that a large number of morphological changes were observated in apoptotic lung cancer cells. Taxol TPP-PEG-PE nanomicelles could significantly increase the pro- apoptotic Caspase-3 activity and reduce the expression of anti-apoptotic protein Bcl-2 and c-IAP1. They were all significantly superior to that of taxol-PEG-PE nanomicelles and taxol group (P < 0.01). Conclusion The taxol TPP-PEG-PE nanomicelles had good mitochondrial targeting of lung cancer cells and promoted the apoptosis of lung cancer cells. It was a potential and efficient drug delivery system for lung cancer cell mitochondria.