Luminescent/magnetic hybrid nanoparticles with folate-conjugated peptide composites for tumor-targeted drug delivery.

We developed a novel chitosan-based luminescent/magnetic hybrid nanoparticles with folate-conjugated tetrapeptide composites (CLMNPs-tetrapeptide-FA) by conjugation in situ. First, chitosan, CdTe quantum dots (QDs), and superparamagnetic iron oxide were directly gelled into ternary hybrid nanogels. Subsequently, tetrapeptides (GFFG and LGPV) and folate were conjugated orderly into the hybrid nanoparticles. The morphology, composition, and properties of the as-prepared copolymers have also been characterized and determined using TEM, EDX, XRD, FTIR spectra, DLS, fluorescence spectroscopy, VSM, and fluorescence microscopy imaging studies. The size range of the end product CLMNPs-tetrapeptide-FA copolymers was from 150 to 190 nm under simulated physiological environment. In vivo, the experimental results of magnetic accumulation showed that the copolymers could be trapped in the tumor tissue under magnetic guidance. Under the present experimental conditions, the loading efficiencies of CPT were approximately 8.6 wt % for CLMNPs-GFFG-FA and 1.1 wt % for CLMNPs-LGPV-FA, respectively. The CPT cumulative release under dialysis condition mainly occurred for the first 28 h, and could reach 55% at pH 5.3 and 46% at pH 7.4 from CPT-loaded CLMNPs-GFFG-FA, and 69% at pH 5.3 and 57% at pH 7.4 from CPT-loaded CLMNPs-LGPV-FA within 28 h, respectively. The hemolysis percentages (<2%) and coagulation properties of blank and CPT-loaded copolymers were within the scope of safe values. Compared to free CPT, the CPT-loaded CLMNPs-tetrapeptide-FA copolymers showed specific targeting to A549 cells in vitro. More than 75% viability in L02 cells were seen in CLMNPs-GFFG-FA and CLMNPs-LGPV-FA copolymer concentration of 500 μg/mL, respectively. It was found that the two kinds of copolymers were transported into the A549 cells by a folate-receptor-mediated endocytosis mechanism. These results indicate that the multifunctional CLMNPs-tetrapeptide-FA copolymers possess a moderate CPT loading efficiency, low cytotoxicity, and favorable biocompatibility, and are promising candidates for tumor-targeted drug delivery.