Exploration And Application Of New Therapeutic Means Of Renal Cell Carcinoma Based On Nano - Drug Delivery System

PEG-IR780-C13 micelles have been demonstrated to be a novel photothermal agent with tumor-targeting property. This study was designed to explore the feasibility of applying PEG-IR780-C13 micelles and near-infrared (NIR) irradiation for thermal ablation of renal tumor by using an in situ tumor model. In addition, the potential thermal injury to normal renal tissue was evaluated. PEG-IR780-C13 micelles intended to accumulate in renal tumor after systematic delivery. In vitro results revealed that PEG-IR780-C13 micelles were uptaked by RENCA cells mainly through caveolae-mediated endocytosis and mainly distributed in late endosomes and lysosomes. Upon NIR irradiation, PEG-IR780-C13 micelles generated heat effectively both in vitro and in vivo, exhibiting promising photothermal therapeutic property. The photothermal effect of PEG-IR780-C13 micelles could effectively destruct RENCA cells in vitro and adequately inhibit growth of in situ renal tumor in vivo. Meanwhile, PEG-IR780-C13 micelles mediated photothermal therapy (PTT) resulted in only limited injury to normal renal tissue surrounding tumor sites without inducing significant renal dysfunction. Our data indicated that PEG-IR780-C13 micelles mediated PTT could generate tumor-specific heat for destruction of renal tumor in a minimally invasive way, providing a novel strategy for thermal ablation of renal tumor.The effect of perfluorochemical preparations in enhancing radiotherapy has been well investigated. However, additional oxygen supply is essential before or during radiotherapy, suggesting the limited efficacy of perfluorochemical preparations. In the present study, perfluocarbon nanoparticles were developed by encapsulating perfluorohexane into liposome (lip(PFH)) to enhance radiotherapy. Renal cell carcinoma xenografts were grown in the flanks of Balb/c mice. After intravenous injection, lip(PFH) could accumulate in the tumor site over time, with a prominent accumulation in tumor 24 h post injection. X-ray was delivered to the tumor site 24 h after the injection of lip(PFH) under room air. The experimental mice were randomized into four groups:control (saline), lip(PFH) (lip(PFH) only), X-ray (X-ray only), and lip(PFH)+X-ray (lip(PFH) with x-ray radiation). Tumor volume and histology were monitored to assess treatment efficacy. Results indicated that tumor growth was significantly reduced in mice received lip(PFH) and X-ray compared with X-ray only. The histological data also revealed more destruction of tumor tissue in Lip(PFH)+X-ray group compared with X-ray only. In addition, Lip(PFH) did not show any significant tissue damage to major organs or induce significant liver/kidney dysfunction.In conclusion,lip(PFH) could accumulate in the tumor site and enhance radiotherapy without additional oxygen supply.