pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer.

摘要: Background Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer thus are target. An acid-activated mitochondria-targeting nanocarrier with redox-responsive function was constructed present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy drug-resistant lung is unknown. Results Acid-cleavable dimethylmaleic anhydride (DA) used modify pluronic P85-conjugated triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP DA-P-SS-T). The nanocarriers demonstrated enhanced cellular uptake selective mitochondrial targeting at extracellular pH characteristic for tumor (6.5) were characterized by extended circulation blood. TPP promoted DA-P-SS-T/PTX nanomicelles outer membrane decrease potential ATP level, resulting inhibition P-glycoprotein suppression resistance metastasis. PTX also rapidly released presence high glutathione (GSH) levels directly diffused into mitochondria, apoptosis cells. Conclusions These promising results indicated that potentially represent significant advancement treatment. GRAPHIC ABSTARCT.