Journal
MOLECULAR THERAPY
Volume 21, Issue 6, Pages 1195-1203Publisher
CELL PRESS
DOI: 10.1038/mt.2013.57
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Funding
- Japan Society for the Promotion of Science (JSPS)
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- MEXT of Japan [2306]
- New Energy and Industrial Technology Development Organization (NEDO)
- Grants-in-Aid for Scientific Research [10J02352, 24107502, 21229002] Funding Source: KAKEN
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Small interfering RNA (siRNA) would be predicted to function as a cancer drug, but an efficient siRNA delivery system is required for clinical development. To address this issue, we developed a liposomal siRNA carrier, a multifunctional envelope-type nanodevice (MEND). We previously reported that a MEND composed of a pH-sensitive cationic lipid, YSK05, showed significant knockdown in both in vitro and in tumor tissue by intratumoral injection. Here, we report on the development of an in vivo siRNA delivery system that is delivered by systemic injection and an analysis of the pharmacokinetics of an intravenously administered siRNA molecule in tumor tissue. Tumor delivery of siRNA was quantified by means of stem-loop primer quantitative reverse transcriptase PCR (qRT-PCR) method. PEGylation of the YSK-MEND results in the increase in the accumulation of siRNA in tumor tissue from 0.0079% ID/g tumor to 1.9% ID/g tumor. The Administration of the MEND (3 mg siRNA/kg body weight) showed about a 50% reduction in the target gene mRNA and protein. Moreover, we verified the induction of RNA interference by 5' RACE-PCR method. The collective results reported here indicate that an siRNA carrier was developed that can deliver siRNA to a target cell in tumor tissue through an improved siRNA bioavailability.
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