Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 63, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2021.102488
Keywords
Non-cationic liposome; siRNA; Photosensitizer; RNAi; Intracellular delivery
Categories
Funding
- JSPS KAKENHI [16H06314, 18K18386]
- Japan Agency for Medical Research and Development (AMED) [17fk0310105h0001, 18jm0610005h0001]
- JGC-S Scholarship Foundation
- Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials (MEXT)
- Grants-in-Aid for Scientific Research [16H06314, 18K18386] Funding Source: KAKEN
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siRNA can specifically suppress gene expression through RNA interference (RNAi), but the efficiency of delivery is low. Researchers have successfully demonstrated highly efficient cytoplasmic delivery of siRNA and observed RNAi phenomena by combining non-cationic liposomes and the photosensitizer AlPcS2a.
Small interfering RNA (siRNA) can specifically suppress gene expression by cleaving mRNA in the cytoplasm, termed RNA interference (RNAi). Although a nanoparticle-based siRNA delivery system has been approved for clinical use, the efficiency of cytoplasmic delivery of siRNA is still low. Recently, our group has established a highly efficient siRNA encapsulation method using non-cationic liposomes (LPs), which are more biocompatible than conventional cationic LPs. While non-cationic LPs containing siRNA were taken up by cells in vitro, the cytoplasmic release of siRNA and subsequent phenomena involving RNAi were not observed. It was considered that cytoplasmic delivery of siRNA, and siRNA release from LPs, should occur sequentially. We utilized amphiphilic photosensitizer Al (III) phthalocyanine chloride disulfonic acid (AlPcS2a), which can generate singlet oxygen under exposure to red light. When SK-HEP-1 cells expressing luciferase were treated with non-cationic LPs containing both siRNA and AlPcS2a, RNAi could be observed upon red light exposure, suggesting that singlet oxygen efficiently disrupts the membranous structures of endo/lysosomes and LPs. Thus, the combined use of AlPcS2a and red light is effective for utilizing non-cationic LPs for cytoplasmic delivery of siRNA.
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