G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma

Abstract

Zhiping Yu,1 Yixuan Wang,2 Dan Xu,3 Lianhua Zhu,3 Ming Hu,1 Qiuli Liu,1 Weihua Lan,1 Jun Jiang,1 Luofu Wang1 1Department of Urology, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2The First Clinical College, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Ultrasound, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Luofu WangDepartment of Urology, Daping Hospital, No. 10 Changjiangzhilu Road, Yuzhong District, Chongqing 400042, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: We intended to design G250 antigen-targeting temsirolimus-loaded nanobubbles (G250-TNBs) based on the targeted drug delivery system and to combine G250-TNBs with ultrasound targeted nanobubble destruction (UTND) to achieve a synergistic treatment for renal cell carcinoma (RCC).Methods: The filming-rehydration method was combined with mechanical shock and electrostatic interactions to prepare temsirolimus-loaded nanobubbles (TNBs). G250-TNBs were prepared by attaching anti-G250 nanobodies to the surface of TNBs using the biotin-streptavidin-bridge method. The ability of G250-TNBs to target the G250 antigen of RCC cells and the synergistic efficacy of G250-TNBs and UTND in the treatment of RCC were assessed.Results: The average diameter of the prepared G250-TNBs was 368.7 ± 43.4 nm, the encapsulation efficiency was 68.59% ± 5.43%, and the loading efficiency was 5.23% ± 0.91%. In vitro experiments showed that the affinity of G250-TNBs to the human RCC 786-O cells was significantly higher than that of TNBs (P <0.05), and the inhibitory effect on 786-O cell proliferation and the induction of 786-O cell apoptosis was significantly enhanced in the group treated with G250-TNBs and UTND (G250-TNBs+ UTND group) compared with the other groups (P <0.05). In a nude mouse xenograft model, compared with TNBs, G250-TNBs could target the transplanted tumors and thus significantly enhance the ultrasound imaging of the tumors. Compared with all other groups, the G250-TNBs+UTND group exhibited a significantly lower tumor volume, a higher tumor growth inhibition rate, and a higher apoptosis index (P <0.05).Conclusion: The combined G250-TNBs and UTND treatment can deliver anti-tumor drugs to local areas of RCC, increase the local effective drug concentration, and enhance anti-tumor efficacy, thus providing a potential novel method for targeted therapy of RCC.Keywords: nanobubble, G250 antigen, nanobody, targeted drug delivery system, renal cell carcinoma, temsirolimus

Keywords

• nanobubble
• g250 antigen
• nanobody
• targeted drug delivery system
• renal cell carcinoma
• temsirolimus