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Background: 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 immunerelated 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.

This research recommended for chin operations in Chinese population: the surgical safe zone could be set in the region about over 4 mm anterior to the mental foramen, and over 12 mm above inferior border of mandible for anterior alveolar surgery, or within 9 mm above inferior border of mandible for genioplasty.