Combined UTMD-Nanoplatform for the Effective Delivery of Drugs to Treat Renal Cell Carcinoma

Abstract

Ting Dai,* Qimeihui Wang,* Lingyu Zhu, Qiang Luo, Jiayu Yang, Xia Meng, Hui Wang, Zhixia Sun Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Wang; Zhixia Sun, Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Email [email protected]; [email protected]: The effective accumulation of nanoparticles (NPs) in the tumour area is an important goals of current nanotechnology research, and a targeted nanoplatform is an effective solution. So we designed a multifunctional sound-sensitive targeted NP that combines a sonosensitizer to enable precisely targeted, deep-penetration sonodynamic therapy (SDT) in combination with multimodal imaging for the diagnosis and monitoring of renal cell carcinoma (RCC).Methods: ZnPP@PP NPs (ZnPP@PLGA- PFP NPs) were prepared via a double emulsion method, and G250 was covalently attached to the NPs shell via the carbon diimide method. Physicochemical property tests were conducted on the ZnPP@G-PP NPs, including tests of particle size, potential distribution, encapsulation efficiency and drug loading capability. We assessed the targeting ability, the production of reactive oxygen species (ROS) and permeability of the NPs in vitro. Moreover, we evaluated the nanoparticle’s multimodal imaging capabilities and therapeutic ability against RCC, both in vitro and in vivo.Results: The Znpp@G-PP NPs were successfully constructed, and their general properties showed uniform particle size, negative potential and good stability. The nanoparticles were successfully loaded with ZnPP and connected with G250, showing tumor-specific targeting ability. Under LIFU irradiation, the nanoparticles produced 1O2 by SDT. For RCC, PA/US multi-modal imaging of Znpp@G-PP NPs provide diagnostic information and monitor therapies in real time in 786-O RCC xenografts, with good biocompatibility. With the UTMD, nanoparticles can be effectively targeted into the tumor cells and penetrate into the tumor interior, significantly improving the SDT effect. Experiments in vitro and in vivo showed that the combination of the nanoparticles and LIFU could suppress the tumor, and the therapeutic effect was confirmed by immunohistochemistry.Conclusion: ZnPP@G-PP NPs provide a promising theranostic strategy for RCC and a platform for further research on improving the efficacy of diagnosis and treatment.Keywords: targeted therapy, deep-penetration, sonodynamic therapy, multimodal imaging

Keywords

• targeted therapy
• deep-penetration
• sonodynamic therapy
• multimodal imaging