Mitochondrial Targeting and pH-Responsive Nanogels for Co-Delivery of Lonidamine and Paclitaxel to Conquer Drug Resistance.

ABSTRACT: Multidrug resistance (MDR) is one of the leading causes of the failure of cancer chemotherapy and mainly attributed to the overexpression of drug efflux transporters in cancer cells, which is dependent on adenosine triphosphate (ATP). To overcome this phenomenon, herein, a mitochondrial-directed pH-sensitive polyvinyl alcohol (PVA) nanogel incorporating the hexokinase inhibitor lonidamine (LND) and the chemotherapeutic drug paclitaxel (PTX) was developed to restore the activity of PTX and synergistically treat drug-resistant tumors. The introduction of 2-dimethylaminoethanethiol (DMA) moiety into the nanogels not only promoted the drug loading capacity but also enabled the lysosomal escape of the nanogels. The subsequent mitochondrial targeting facilitated the accumulation and acid-trigger

SUBMITTER: Chen E 

PROVIDER: S-EPMC8667579 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature