131I-Traced PLGA-Lipid Nanoparticles as Drug Delivery Carriers for the Targeted Chemotherapeutic Treatment of Melanoma

Haiyan Wang, Weizhong Sheng

Herein, folic acid (FA) conjugated Poly(d,l-lactide-co-glycolide) (PLGA)-lipid composites (FA-PL) were developed as nanocarriers for the targeted delivery of insoluble anti-cancer drug paclitaxel (PTX), resulting FA-PLP nanoparticles. Furthermore, (131)I, as a radioactive tracer, was used to label FA-PLP nanoparticles (FA-PLP-(131)I) to evaluate their cell uptake activity, in vivo blood circulation, and biodistribution. The FA-PLP-(131)I nanoparticles had a spherical morphology with great stability, a narrow size distribution (165.6 and 181.2 nm), and -22.1 mV in average zeta potential. Confocal laser scanning microscopy indicated that the targeting molecule FA promotes PLP-(131)I uptake by melanoma B16F10 cells, which was further confirmed by the cell incorporation rate via (131)I activity detection as measured by a gamma counter. FA-PLP-(131)I without PTX (FA-PL-(131)I) shows minor cytotoxicity, good biocompatibility, while FA-PLP-(131)I was demonstrated to have efficient cell viability suppression compared to free PTX and PLP-(131)I. Following intravenous injection, the blood circulation half-life of free PTX (t 1/2 = 5.4 ± 0.23 h) was prolonged to 18.5 ± 0.5 h by FA-PLP-(131)I. Through FA targeting, the tumor uptake of FA-PLP-(131)I was approximately 4.41- and 12.8-fold higher compared to that of PLP-(131)I and free PTX-(131)I, respectively. Moreover, following 40 days of treatment, FA-PLP-(131)I showed an improved tumor inhibition effect compared to free PTX and PLP-(131)I, with no relapse and no remarkable systemic in vivo toxicity. The results demonstrate that the (131)I-labeled PLGA-lipid nanoparticle can be simultaneously applied for targeted drug delivery and reliable tracking of drugs in vivo.