Apoferritin encapsulation of cysteine protease inhibitors for cathepsin L inhibition in cancer cells.

ABSTRACT: Cysteine proteases play a key role in tumorigenesis causing protein degradation and promoting invasive tumour growth. Cathepsin L is overexpressed in cancer cells and could provide a specific target for delivery of anticancer agents. We encapsulated novel dipeptidyl nitrile based cysteine protease inhibitors (Neq0551, Neq0554 and Neq0568) into biocompatible apoferritin (AFt) protein nanocages to achieve specific delivery to tumours and pH-induced drug release. AFt-encapsulated Neq0554 demonstrated ∼3-fold enhanced in vitro activity (GI₅₀ = 79 μM) compared to naked agent against MiaPaCa-2 pancreatic carcinoma cells. Selectivity for cancer cells was confirmed by comparing their activity to non-tumourigenic human fibroblasts (GI₅₀ > 200 μM). Transferrin receptor (

SUBMITTER: Quilles Junior JC 

PROVIDER: S-EPMC9075514 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature