Enhancing precision medicine: Bispecific antibody-mediated targeted delivery of lipid nanoparticles for potential cancer therapy

被引:4
作者
Zhang, Yue [1 ]
Gu, Xiaoyan [1 ]
Huang, Lili [1 ]
Yang, Yani [1 ]
He, Jun [1 ]
机构
[1] Natl Adv Med Engn Res Ctr, China State Inst Pharmaceut Ind, 285 Gebaini Rd, Shanghai 201203, Peoples R China
关键词
Lipid nanoparticles; Bispecific antibody; GRP78; protein; Tumor cells; Tumor target; CELL-SURFACE GRP78; ADSORPTION; MIGRATION; CHAPERONE; MARKER; LIGAND;
D O I
10.1016/j.ijpharm.2024.123990
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The precise delivery of therapeutic agents to specific cell populations, including cancer cells, remains a target in modern medicine, to enhance treatment efficacy, while minimizing unintended side effects. This study presents a strategy utilizing bispecific antibodies for the targeted delivery of nucleic acid drugs to the surface of glucoseregulated protein 78 (GRP78)-overexpressing cancer cells. Strong binding affinity of the bispecific antibodies to GRP78-overexpressing cancer cells, including HEPG2 cells, confirmed the tumor-targeting potential of this platform. Functional analyses demonstrated the role of the bispecific antibodies in enhancing lipid nanoparticle (LNP) uptake, causing increased gene expression levels of nucleic acid drugs loaded within LNPs. In vivo imaging confirmed the potency of the bispecific-antibody-modified LNPs in delivering nucleic acid drugs to tumors and sustaining therapeutic expression levels. In vivo therapy results indicated that the bispecific antibodies improved the antitumor activity of PE38-loaded LNPs in tumors overexpressing surface GRP78. This study pioneered a bispecific-antibody-centered platform for the targeted delivery of nucleic acid drugs. The robust antigen-antibody binding affinity, tumor-selective interactions, enhanced cellular uptake, and proficient gene expression promise to advance precision therapeutics in oncology. Continued refinement and translation of this drug delivery strategy are important to unlock its full clinical potential.
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页数:10
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