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您的检索式：作者名="Rebecca MHaley"
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| 1 | Doxorubicin-conjugated siRNA lipid nanoparticles for combination cancer therapy显示文摘Evasion of apoptosis is a hallmark of cancer,attributed in part to overexpression of the antiapoptotic 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 systems 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 encapsulation 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 siRNAloaded 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. | Kamila Butowska Xuexiang Han Ningqiang Gong Rakan El-Mayta Rebecca MHaley Lulu Xue Wenqun Zhong Wei Guo Karin Wang Michael J.Mitchell | 2023 | Acta Pharmaceutica Sinica B2023，13，4： | 1 |
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