iRGD-paclitaxel conjugate nanoparticles for targeted paclitaxel delivery.

Paclitaxel (PTX) is a chemotherapeutic agent which shows antitumor activities against a broad spectrum of cancers. Yet, the current formulation of PTX used in clinic may cause a number of adverse reactions, which significantly limit its application. To obtain better clinical use of PTX, we report, for the first time, iRGD-PTX conjugate nanoparticles (NPs) for targeted PTX delivery. iRGD-PTX conjugate was synthesized from thiolated iRGD and 6-maleimidocaproic acid-PTX through Michael addition reaction. iRGD-PTX NPs with hydrodynamic diameter of ~110 nm were self-assembled from iRGD-PTX conjugate in deionized water. The as-prepared iRGD-PTX NPs exhibit good stability in phosphate buffered saline (PBS) buffer and fetal bovine serum containing PBS buffer. iRGD-PTX NPs exhibit sustained drug release behaviors. The in vitro studies show that iRGD-PTX NPs can be internalized by 4T1 cells by integrin αV-mediated endocytosis, resulting in better in vitro antitumor activity as compared to free PTX. The in vivo studies demonstrate that iRGD-PTX NPs exhibit enhanced tumor accumulation. The iRGD-PTX NPs reported here represent a novel PTX nanoplatform to achieve targeted PTX delivery.