Loading...
Doxorubicin-conjugated siRNA lipid nanoparticles for combination cancer therapy
Butowska, Kamila Han, Xuexiang Gong, Ningqiang El-Matya, Rakan Haley, Rebecca M. Xue, Lulu Zhong, Wenqun Guo, Wei Mitchell, Michael J.
Butowska, Kamila
Han, Xuexiang
Gong, Ningqiang
El-Matya, Rakan
Haley, Rebecca M.
Xue, Lulu
Zhong, Wenqun
Guo, Wei
Mitchell, Michael J.
Citations
Altmetric:
Genre
Journal article
Date
2023-04-19
Advisor
Committee member
Group
Department
Bioengineering
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
http://dx.doi.org/10.1016/j.apsb.2022.07.011
Abstract
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 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 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.
Description
Citation
Kamila Butowska, Xuexiang Han, Ningqiang Gong, Rakan El-Mayta, Rebecca M. Haley, Lulu Xue, Wenqun Zhong, Wei Guo, Karin Wang, Michael J. Mitchell, Doxorubicin-conjugated siRNA lipid nanoparticles for combination cancer therapy, Acta Pharmaceutica Sinica B, Volume 13, Issue 4, 2023, Pages 1429-1437, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2022.07.011.
Citation to related work
Elsevier
Has part
Acta Pharmaceutica Sinica B (APSB), Vol. 13, Iss. 4
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu