期刊
NANO LETTERS
卷 16, 期 11, 页码 6916-6923出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.6b02915
关键词
Cytosolic release; low internalization; low doses; high efficiency; siRNA delivery; monoblastic cell
类别
资金
- National High Technology Research and Development Program of China [2012AA022501]
- National Natural Science Foundation of China [31271073, 81273422, 81371667, 81473128, 81402863]
The extremely low efficient cytosolic release of the internalized siRNA has emerged recently as a central issue for siRNA delivery, while there is a lack of guidelines to facilitate the cytosolic release of internalized siRNA. To address these concerns, we studied the contribution of the pH-sensitive inner core on handling the cytosolic release of siRNA delivered by a series of PG-P(DPAx-co-DMAEMAy)-PCB amphiphilic polycation nanomicelles (GDDC-Ms) with extremely low internalization (<1/4 of lipofactamine 2000 (Lipo2000)). Significantly, just by varying the mole ratio of DPA and DMAEMA to adjust the initial disassembly pH (pH(dis)) of the core near to 6.8, GDDC(4)-Ms/siRNA could get nearly 98.8% silencing efficiency at w/w = 12 with 50 nM siRNA and similar to 78% silencing efficiency at w/w = 30 with a very low dose of 5 nM siRNA in HepG-2 cell lines, while Lipo2000 only got 65.7% with 50 nM siRNA. Furthermore, similar to 98.4% silencing efficiency was also realized in the hard-to-transfect human acute monoblastic leukemia cell line U937 by GDDC(4)-Ms/siRNA (at w/w = 15, 50 nM siRNA), in the inefficient case for Lipo2000. Additionally, the high silencing efficiency (similar to 80%) in skin tissue in vivo was discovered. Undoubtedly, the robust potential of GDDC(4)-Ms in handling the cytosolic release paves a simple but efficient new way for the design of the nonviral siRNA vector.
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