Nanocarriers for cancer-targeted delivery based on Pickering emulsions stabilized by casein nanoparticles

This study demonstrates the development of stimuli-responsive Pickering emulsions stabilized by casein nanoparticles (CNPs) for targeted drug delivery to colorectal cancer cells (CRC). Encapsulation of a fluorescent dye simulates therapeutic delivery, demonstrating biomedical potential. The oil-in-water nanoemulsions stabilized by CNPs function as nanocarriers sensitive to matrix metalloproteinase-7 (MMP-7), an enzyme overexpressed in CRC cells, enabling precise drug release. Emulsions exhibited strong stability due CNPs forming a robust layer at the oil-water interface, enhancing bioavailability and controlled release. Covalent modifications of CNPs with polyethyleneimine (PEI) or polyacrylic acid (PAA), and pH adjustments optimize the zeta potential, improving surface charge and delivery efficiency. Maximal CNP uptake occurred with PAA-modified CNPs (−20 mV), showing superior interaction with CRC cells compared to pristine (−6.7 mV) and PEI-modified (+30.5, +42.1 mV) CNPs. Confocal microscopy and imaging flow cytometry confirmed that CNP-stabilized emulsions enhance CRC inter-localization compared to dispersed CNPs. Nanoemulsions with the highest CNP uptake showed selective interaction with tumor cells, while minimizing oil droplet uptake, driven by nanoscale dimensions and targeted surface interactions. Enzymatic degradation of CNPs by MMP-7 induces phase separation and targeted release. This dual-functional system, leveraging charge modification and enzymatic responsiveness, highlights CNP-stabilized nanoemulsions as a promising CRC-targeted drug delivery platform.