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

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, I-131, as a radioactive tracer, was used to label FA-PLP nanoparticles (FA-PLP-I-131) to evaluate their cell uptake activity, in vivo blood circulation, and biodistribution. The FA-PLP-I-131 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-I-131 uptake by melanoma B16F10 cells, which was further confirmed by the cell incorporation rate via I-131 activity detection as measured by a gamma counter. FA-PLP-I-131 without PTX (FA-PL-I-131) shows minor cytotoxicity, good biocompatibility, while FA-PLP-I-131 was demonstrated to have efficient cell viability suppression compared to free PTX and PLP-I-131. 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-I-131. Through FA targeting, the tumor uptake of FA-PLP-I-131 was approximately 4.41- and 12.8-fold higher compared to that of PLP-I-131 and free PTX-I-131, respectively. Moreover, following 40 days of treatment, FA-PLP-I-131 showed an improved tumor inhibition effect compared to free PTX and PLP-I-131, with no relapse and no remarkable systemic in vivo toxicity. The results demonstrate that the I-131-labeled PLGA-lipid nanoparticle can be simultaneously applied for targeted drug delivery and reliable tracking of drugs in vivo.