pH-Responsive Lipid Nanocapsules: A Promising Strategy for Improved Resistant Melanoma Cell Internalization

Abstract

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.

Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity

“…It has the effect of stabilizing the organometallic quinone methide that is the highly active primary metabolite, while acting as a brake on the formation of competing secondary and counterproductive metabolites, as we have shown elsewhere [ 17 , 18 ]. However, it is not known whether this behavior retains its advantages in vivo if a new type of stable vehicle is used, rather than the fragile lipid nanocapsules (LNC) that are typically used with ferrocifens [ 19 , 20 ]. This is the question that is addressed herein within the framework of the preclinical trial we developed.…”

Engineering Hyaluronic Acid Microneedles Loaded with Mn2+ and Temozolomide for Topical Precision Therapy of Melanoma

“…[ 1 ] Nevertheless, chemotherapy usually brings the side effects such as alopecia and bone marrow suppression, which seriously affects the life quality and causes extreme pain to the patients. [ 2 ] Consequently, target‐modified nanocarriers [ 3 ] and stimulus‐responsive release strategies [ 4 ] have been developed to solve these problem and enhance the curative effect. These strategies released the drugs at the site of the lesion to specifically kill the tumor, while they are still also hindered by low drug encapsulation rates and high production costs.…”

Lipid and Polymeric Nanocapsules

“…In the case of melanoma therapy, lipid nanocapsules prepared from N-vinylpyrrolidone and vinyl imidazole showed pH-responsive ability and improved drug entrance into the tumoral cells. The copolymers were inserted into the surface of the nanocapsules, and they particularly changed from neutral charge at physiological pH to positive charge in acid conditions [114]. Besides, polyurea/polyurethane nanocapsules displaying pH-synchronized amphoteric properties were proposed.…”