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Cellular uptake and fate of cationic polymer-coated nanodiamonds delivering siRNA: a mechanistic study
Gene silencing using small interfering RNAs (siRNAs) is a selective and promising approach for treatment of numerous diseases. However, broad applications of siRNAs are compromised by their low stability in a biological environment and limited ability to penetrate cells. Nanodiamonds (NDs) coated wi...
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Published in: | Nanoscale 2024-02, Vol.16 (5), p.249-253 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Gene silencing using small interfering RNAs (siRNAs) is a selective and promising approach for treatment of numerous diseases. However, broad applications of siRNAs are compromised by their low stability in a biological environment and limited ability to penetrate cells. Nanodiamonds (NDs) coated with cationic polymers can enable cellular delivery of siRNAs. Recently, we developed a new type of ND coating based on a random copolymer consisting of (2-dimethylaminoethyl) methacrylate (DMAEMA) and
N
-(2-hydroxypropyl) methacrylamide (HPMA) monomers. These hybrid NDpolymer particles (Cop
+
-FND) provide near-infrared fluorescence, form stable complexes with siRNA in serum, show low toxicity, and effectively deliver siRNA into cells
in vitro
and
in vivo
. Here, we present data on the mechanism of cellular uptake and cell trafficking of Cop
+
-FND:siRNA complexes and their ability to selectively suppress mRNA levels, as well as their cytotoxicity, viability and colloidal stability. We identified clathrin-mediated endocytosis as the predominant entry mechanism for Cop
+
-FND:siRNA into U-2 OS human bone osteosarcoma cells, with a substantial fraction of Cop
+
-FND:siRNA following the lysosome pathway. Cop
+
-FND:siRNA potently inhibited the target GAPDH gene with negligible toxicity and sufficient colloidal stability. Based on our results, we suggest that Cop
+
-FND:siRNA can serve as a suitable
in vivo
delivery system for siRNA.
Nanodiamonds coated with a random cationic copolymer based on (2-dimethylaminoethyl) methacrylate (DMAEMA) and
N
-(2-hydroxypropyl) methacrylamide (HPMA) enable highly effective cellular delivery of siRNAs. Clathrin-mediated endocytosis is the predominant entry mechanism. |
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ISSN: | 2040-3364 2040-3372 |
DOI: | 10.1039/d3nr05738k |