Although
local anesthetics (LAs) such as
lidocaine have been traditionally used for
pain relief, their antitumor activity has attracted more and more attentions in recent years. However, since nearly all LAs used in clinic are in their hydrochloride forms with small molecular weight and high water-solubility, their fast absorption and clearance greatly limit their antitumor activity in vivo. To better exploit the antitumor activity of LAs,
lidocaine nanoparticles (LNPs) are prepared by using a self-assembling
peptide to encapsulate the hydrophobic base form of
lidocaine. In cultured A375 human
melanoma cells, the LNPs show much higher cellular uptake level than the clinic formulation of
lidocaine hydrochloride, which leads to enhanced efficacy in inhibiting the proliferation, migration and invasion of the cells, as well as in inducing cell apoptosis. Compared with
lidocaine hydrochloride, LNPs can also significantly slow down the release rate of
lidocaine. In nude mice, LNPs can effectively inhibit the development of solid
tumors from seeded A375 cells and prevent the recurrence of
tumors after surgical excision. These results indicate that by using self-assembling
peptide to fabricate nanoparticle formulations of
local anesthetics, their antitumor activity can be significantly enhanced, suggesting a potential postoperative treatment to prevent
tumor recurrence after surgical excision.