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Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy
Yu-E Qin1, Wen-Fan Tang1, Yun Xu1
1Department 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.
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 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.
Insights
This study shows ultrasound-targeted microbubbles can deliver miR-34a and sPD-1 to reduce cervical cancer growth, induce apoptosis, and boost anti-tumor immunity in mice.
Area of Science:
- Oncology
- Biotechnology
- Nanomedicine
Background:
- Cervical cancer exhibits reduced miR-34a and elevated PD-L1, necessitating targeted therapies.
- Current cervical cancer treatments lack precision and targeted approaches.
Purpose of the Study:
- To explore ultrasound-mediated co-delivery of miR-34a and sPD-1 using microbubbles for synergistic cancer therapy.
- To investigate the therapeutic potential of cationic lipid microbubbles (CLMBs) for targeted drug delivery in cervical cancer models.
Main Methods:
- Cationic lipid microbubbles (CLMBs) were synthesized and loaded with miR-34a and sPD-1.
- Ultrasound-targeted destruction was employed for localized delivery in U14 xenograft mice.
- Tumor volume, weight, apoptosis (TUNEL, Bcl-2, Bax mRNA), and immune responses (IFN-γ, CTL) were assessed.
Main Results:
- CLMBs successfully bound and delivered miR-34a and sPD-1, leading to significant reduction in tumor volume and weight.
- The treatment induced apoptosis by downregulating Bcl-2 and upregulating Bax.
- Ultrasound-mediated delivery enhanced anti-tumor immunity, evidenced by increased IFN-γ and cytotoxic T lymphocytes (CTL).
Conclusions:
- CLMBs serve as effective carriers for co-delivering miR-34a and sPD-1.
- Ultrasound-targeted destruction of CLMBs suppresses tumor growth, induces apoptosis, and enhances anti-tumor immunity in cervical cancer xenografts.
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