Targeted Nanobubbles of PD-L1 mAb Combined with Doxorubicin as a Synergistic Tumor Repressor in Hepatocarcinoma

• DOI: 10.2147/ijn.s376172
• Publication Date: 2022-09-06T12:30:22Z
• Authors: Yezi Chen; Xiaoqin Luo; Yun Liu; Yunlei Zou; Shiqi Yang; Chaoqi Liu; Yun Zhao
• Keywords: Medicine (General); tumor immune therapy; Carcinoma, Hepatocellular; Liver Neoplasms; Antibodies, Monoclonal; Biotin; B7-H1 Antigen; 3. Good health; immune checkpoint inhibitors; 03 medical and health sciences; R5-920; 0302 clinical medicine; International Journal of Nanomedicine; Doxorubicin; Cell Line, Tumor; immunogenic cell death; drug delivery; Animals; ultrasound targeted nanobubble destruction; Original Research

Ultrasound nanobubbles (NBs) can kill tumor cells, mediated by their effects of cavitation and acoustic perforation through ultrasound, while as novel drug carriers, biomaterial-modified NBs release drugs at a target region. In this work, the ultrasound bridged biotin-streptavidin were prepared simultaneously to be loaded with both programmed death ligand 1 monoclonal antibody (PD-L1 mAb) doxorubicin (DOX), which are immune checkpoint inhibitors (ICIs) chemotherapeutic agents, synergize immunotherapy chemotherapy combined sonodynamic therapy (SDT).The PD-L1 mAb/DOX NBs, using bridging affinity biotin (BRAB) technology bridge, thin-film hydration mechanical oscillation for targeted delivery biotinylated mAb DOX. Characterization pharmacokinetic studies performed in vitro vivo. The antitumor effect ultrasound-mediated mAb/DOX-NBs was studied subcutaneously transplanted H22 hepatoma model, mechanism synergistic repression investigated.The data targeting experiments, contrast-enhanced imaging (CEUS), vivo small animals system (IVIS), frozen sections showed that have well-targeted aggregation tumor. By observing inhibition rate, tissue cell apoptosis, apoptosis-related gene protein expression, group best effects, its volume mass rates about 69.64% 75.97%, respectively (P < 0.01). Therefore, blocking PD-1/PD-L1 pathway could improve cells' tumor-killing ability. Antitumor cytokines further enhanced when DOX-induced apoptosis immunogenic (ICD).In summary, significant providing potential strategy HCC.