Drug Delivery Using Nanocarriers Self-Assembled by Triskelion Aromatic Molecules

Here we present a new drug delivery nanocarrier constructed by an efficient and facile self-assembling system. A simple triskelion Fmoc-conjugate is designed to rapidly self-assemble into nanoparticles in water. To stabilize the nanoparticles at physiological pH, an Fmoc-dipeptide is employed to bind to the nanoparticles. The fabricated two-component nanoparticles were found to be size-controllable within the range from 53 nm to 125 nm, well-tolerated by cells, and stable upon heating, long-time incubation and dilution. Moreover, these novel particles were readily decorated by short Fmoc-peptides as targeting ligands. We further demonstrated that the two-component nanoparticles could entrap poorly-soluble anticancer drug, paclitaxel (PTX), with a high loading efficiency. With Fmoc-FRGD modifying the nanocarriers to target integrin overexpressed on tumor cells, PTX-loaded nanoparticles showed better in vitro anti-cancer effects than free PTX, with IC₅₀ value of about 3 nM against MDA-MB-435 breast carcinoma cells. The PTX-loaded nanoparticles were stable after 3 days of incubation at 37 ^oC with FBS-supplemented medium. Furthermore, Fmoc-FRGD stabilized nanoparticles were differentially taken up by MDA-MB-435 cells but Fmoc-FRDG stabilized nanoparticles not, which verifies the targeting property of Fmoc-FRGD stabilized nanoparticles. All these attractive characteristics make the novel nanoparticles a promising drug delivery carrier for anticancer therapy.