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Metallic Cation-Mediated Entrapment of Nucleic Acids on Mesoporous Silica Surface: Application in Castration-Resistant Prostate Cancer

Journal Article · · Chemistry of Materials
The use of exogenous nucleic acid technologies to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for the treatment of diseases such as advanced prostate cancer (PC). The promise of nucleic-based therapeutics is dependent on the development of platforms that effectively protect nucleic acids from nuclease degradation and deliver the nucleic acids to the cytosol of target cells. In this work, we present the development of a divalent metal-mediated nucleic acid entrapment strategy with a porous silica matrix. This simple strategy results in efficient loading percentages of both siRNA (>60%) and mRNA (>80%) as well as their release within relevant biological environments (80%). Additionally, our data supports that the current method reduces endosomal entrapment and supports the lipid coating of mesoporous silica nanoparticles (LC-MSNs). Finally, the metal-enhanced nanosystem is assessed for biocompatibility, stability, and circulation within in vitro, ex ovo, and in vivo models of PC.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
Center for Metals and Biology and Medicine; National Aeronautics and Space Administration (NASA); National Cancer Institute (NCI); National Institutes of Health (NIH); National Science Foundation (NSF); USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)
Grant/Contract Number:
89233218CNA000001; NA0003525
OSTI ID:
2472587
Report Number(s):
LA-UR--23-33127
Journal Information:
Chemistry of Materials, Journal Name: Chemistry of Materials Journal Issue: 24 Vol. 35; ISSN 0897-4756
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English

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