Tumor Accumulation, Penetration, and Antitumor Response of Cisplatin-Loaded Gelatin/Poly(acrylic acid) Nanoparticles

摘要

In this report, the cisplatin (CDDP)-loaded gelatin/ poly(acrylic acid) (GEL-PAA) nanoparticles with a spherical shape and drug loading content of 24.6% were prepared. In vivo near-infrared fluorescence (NIRF) imaging and ex vivo gamma scintillation counting analyses reveal that CDDP-loaded GEL-PAA nanoparticles have prominent passive tumor-targeting ability and the nontarget nanoparticles can be readily excreted from the body. Further, it is demonstrated that the CDDP-loaded nanoparticles have the ability to penetrate the tumor after their extravasation through the leaky vessels and distribute in a distance of about 20 μm from the vessels at 24 h postinfection. The in vivo antitumor responses reveal that the nanoparticle formulation exhibits significantly superior in vivo antitumor effect than free CDDP by the comparison of tumor volume and the examinations of cell apoptosis and proliferation in tumor tissues through proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl-transferase-mediated nick end labeling (TUNEL) methods.