Cancer Management and Research (Apr 2020)
Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy
Abstract
Yu-e Qin,* Wen-fan Tang,* Yun Xu, Fu-rong Wan, Ai-hua Chen Department of Gynecology and Obstetrics, The People’s Hospital of China Three Gorges University/The First People’s Hospital of Yichang, Yichang 443000, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai-hua ChenDepartment of Gynecology and Obstetrics, The People’s Hospital of China Three Gorges University/The First People’s Hospital of Yichang, No. 4, Hudi Street, Yichang City, Hubei Province, People’s Republic of ChinaTel +8613972602239Fax +86717-6221636Email [email protected]: miR-34a was downregulated and PD-L1 was upregulated in cervical cancer; however, the treatment of cervical cancer lacks precision and targeting. This study explored the ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles for synergistic cancer therapy.Methods: Cationic lipid microbubbles (CLMBs) were prepared by membrane hydration and mechanical oscillation. U14 subcutaneous xenograft mice were injected with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and tumor volume and tumor weight of mice were measured. TUNEL apoptosis test and the mRNA expression of apoptosis-related gene Bcl-2 and Bax were analyzed by qRT-PCR. Antitumor immune-related cytokines IFN-γ were investigated by qRT-PCR, LDH Cytotoxicity Assay Kit were performed to test cytotoxic T lymphocytes (CTL).Results: CLMBs were successfully prepared and the plasmid bound to its surface. The tumor volume and weight were specifically decreased by ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles, apoptosis was induced and the apoptosis suppressor gene Bcl-2 was downregulated and proapoptotic gene Bax were upregulated. qRT-PCR analysis revealed that antitumor immunity-related IFN-γ was strongly upregulated in mice, which were treated with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and the percentage of CTL was increased.Conclusion: These findings from the study demonstrated that CLMBs could deliver miR-34a and sPD-1, combined with ultrasound targeted destruction, could suppress the tumor tissue growing, induce apoptosis and enhance antitumor immunity in U14 subcutaneous xenograft mice.Keywords: miR-34a, sPD-1, microbubbles, ultrasound, cervical cancer, cancer therapy
