Macropinocytic Uptake and pH-Responsive Endolysosomal Processing Drive Sustained Chemotherapeutic Efficacy of High-Load Core@Shell Nanocarriers in Colorectal Cancer.

ABSTRACT: Poor tumor targeting, strong toxic side effects, and high drug resistance remain clinical challenges for conventional chemotherapy. Here, it is reported that drug-cocktail core@shell nanocarriers are developed for the codelivery of lipophilic irinotecan (ITC) and the hydrophilic 5-fluorouracil (5-FU) metabolite (FdUMP), a commonly used combination in chemotherapy regimens for colorectal cancer. With a drug loading of 57% by mass, these nanocarriers achieve one of the highest reported drug payloads for a chemotherapeutic drug cocktail. Crucially, using a probe-based imaging strategy with mechanistically responsive fluorescent reporters, we found that after slow uptake predominantly via macropinocytosis, the nanocarriers rapidly traffic to endolysosomal compartments, where the acidic environ

SUBMITTER: Choezom D 

PROVIDER: S-EPMC12794672 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature