Despite significant advances in
melanoma therapy, low response rates and multidrug resistance (MDR) have been described, reducing the anticancer efficacy of the administered molecules. Among the causes to explain these resistances, the decreased intratumoral pH is known to potentiate MDR and to reduce the sensitivity to anticancer molecules. Nanomedicines have been widely exploited as the carriers of MDR reversing molecules.
Lipid nanocapsules (LNC) are nanoparticles that have already demonstrated their ability to improve
cancer treatment. Here, LNC were modified with novel copolymers that combine
N-vinylpyrrolidone (NVP) to impart stealth properties and vinyl
imidazole (Vim), providing pH-responsive ability to address classical chemoresistance by improving
tumor cell entry. These copolymers could be post-inserted at the LNC surface, leading to the property of going from neutral charge under physiological pH to positive charge under acidic conditions. LNC modified with
polymer P5 (C18H37-P(NVP21-co-Vim15)) showed in vitro pH-responsive properties characterized by an enhanced cellular uptake under acidic conditions. Moreover, P5 surface modification led to an increased
biological effect by protecting the nanocarrier from opsonization by complement activation. These data suggest that pH-sensitive LNC responds to what is expected from a promising nanocarrier to target metastatic
melanoma.