Delivery of sPD1 gene by anti-CD133 antibody conjugated microbubbles combined with ultrasound for the treatment of cervical cancer in mice

• Published in: Toxicology and applied pharmacology Vol. 474; p. 116605
• Main Authors: Liu, Yun, Zheng, Zhiwei, Han, Jiaxuan, Lin, Chen, Liu, Chaoqi, Ma, Yao, Zhao, Yun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2023
• Subjects: Animals; Cell Line, Tumor; Female; Gene therapy; Humans; Immunoregulation; Mice; Microbubbles; Targeted microbubbles; Tumor; Tumor Microenvironment; Ultrasonography; Ultrasound; Uterine Cervical Neoplasms - diagnostic imaging; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - therapy; Tumor; Gene therapy; Targeted microbubbles; Immunoregulation; Ultrasound
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2023.116605

To explore new therapeutic options for cervical cancer, the inhibitory effect on cervical cancer of targeted CD133-loaded sPD1 gene microbubbles (MBs) combined with low-frequency ultrasound was studied and its mechanism was explored. We prepared microbubbles conjugated with anti-CD133 antibody to deliver the sPD1 gene and determined concentration, particle size, and potentials of MBs. In addition, we verified that CD133 targeted-MBs could specifically bind to U14 cervical cancer cells in vitro. A mouse model of subcutaneous xenograft cervical cancer was established and mice were divided into a control group, an non-targeted microbubble group, a CD133-MBs group, an sPD1-MBs group and a CD133/sPD1-MBs group. Compared with the control group, tumor growth was inhibited in each group, with the CD133/sPD1 group showing the strongest inhibitory effect after treatment. The tumor volume and weight inhibition rates in the CD133/sPD1-MBs group were 78.01% and 72.25% respectively, which were statistically different from the other groups (P < 0.05), and HE staining and TUNEL immunofluorescence showed necrosis and apoptosis in tumor tissue. Flow cytometry, lactate dehydrogenase, and indirect immunofluorescence experiments showed that T lymphocytes were activated and a large number of CD8-positive T cells infiltrated the tumor tissue after treatment, with the CD133/sPD1-MBs group showing the most prominent effects (P < 0.05). The combination of ultrasound with anti- CD133 antibody-conjugated microbubbles loaded with the sPD1 gene can inhibit the growth of cervical cancer, suggesting that the immunosuppressive microenvironment of the tumor is improved after treatment. •We rationally designed a type of multi-functional microbubbles.•We successfully down-regulate expression of PD-L1 and CD133.•sPD1/Anti-CD133 Ab-MBs could activate anti-tumor immune response.•sPD1/Anti-CD133 Ab-MBs could inhibit cervical cancer stemness.•sPD1/Anti-CD133 Ab-MBs could inhibit the growth of cervical cancer.