A quantitative study of the intracellular fate of pH-responsive doxorubicin-polypeptide nanoparticles.

ABSTRACT: Nanoscale carriers with an acid-labile linker between the carrier and drug are commonly used for drug delivery. However, their efficacy is potentially limited by inefficient linker cleavage, and lysosomal entrapment of drugs. To address these critical issues, we developed a new imaging method that spatially overlays the location of a nanoparticle and the released drug from the nanoparticle, on a map of the local intracellular pH that delineates individual endosomes and lysosomes, and the therapeutic intracellular target of the drug-the nucleus. We used this method to quantitatively map the intracellular fate of micelles of a recombinant polypeptide conjugated with doxorubicin via an acid-labile hydrazone linker as a function of local pH and time within live cells. We found that hydrolysis

SUBMITTER: Wang J 

PROVIDER: S-EPMC6372108 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature