期刊
ACTA PHARMACEUTICA SINICA B
卷 13, 期 4, 页码 1429-1437出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2022.07.011
关键词
Lipid nanoparticles; Doxorubicin; Bcl-2; siRNA delivery; Chemotherapy; Lymphoma
Evasion of apoptosis is a characteristic of cancer, and overexpression of Bcl-2 is a contributing factor. Therapeutic targeting of Bcl-2 has shown efficacy in the clinic and is being extensively tested in combination with chemotherapy. Therefore, developing co-delivery systems for Bcl-2 targeting agents and chemotherapeutics, such as LNPs, holds promise for combination cancer therapies.
Evasion of apoptosis is a hallmark of cancer, attributed in part to overexpression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). In a variety of cancer types, including lymphoma, Bcl-2 is overexpressed. Therapeutic targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with chemotherapy. Therefore, the development of co-delivery sys-tems for Bcl-2 targeting agents, such as small interfering RNA (siRNA), and chemotherapeutics, such as doxorubicin (DOX), holds promise for enabling combination cancer therapies. Lipid nanoparticles (LNPs) are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encap-sulation and delivery. Inspired by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs, here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNA-loaded LNPs. Our optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts' lymphoma (Raji) cells, leading to effective inhibition of tumor growth in a mouse model of lymphoma. Based on these results, our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.(c) 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sci-ences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据