期刊
JOURNAL OF CONTROLLED RELEASE
卷 137, 期 3-4, 页码 234-240出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2009.04.006
关键词
Accelerated blood clearance (ABC) phenomenon; Polyethylene glycol (PEG); Anti-PEG IgM; PEG-coated siRNA/cationic liposome complex (PSCL); Small interfering RNA (siRNA)
资金
- Ministry of Education, Culture, Sports and Technology [20015033]
- Grants-in-Aid for Scientific Research [20015033] Funding Source: KAKEN
For efficient delivery of small interfering RNA (siRNA) in vivo, it is important to control the blood circulation of the delivery vehicle. Surface modification of the siRNA/cationic liposome complex (siRNA-lipoplex) with polyethylene glycol (PEG) is expected to enhance circulation time in blood. However, we have recently reported that anti-PEG IgM production after the first injection of PEG-coated liposome is responsible for a reduction in the blood circulation of the second dose of the liposome, which is known as the accelerated blood clearance (ABC) phenomenon. It is unknown whether a PEG-coated siRNA-lipoplex (PSCL) can cause the ABC phenomenon and anti-PEG IgM production. In this study, an anti-PEG IgM response to PSCL was detected and was inversely related to the PSCL dose. Interestingly, the anti-PEG IgM response was significantly lower for PSCL than it was for PEG-coated naked cationic liposomes (PCL). The studies with splenectomized mice and nude mice indicated that anti-PEG IgM production was closely related to an interaction of PSCL and PCL with the spleen, which is associated with a T cell-independent mechanism. In addition, PSCL induced apoptosis on IgM-expressing splenic cells more strongly than PCL did, which suggests that accumulation in the spleen and the apoptotic effect of PEG-coated substances on splenic B cells could affect the potency of anti-PEG IgM production. (C) 2009 Elsevier B.V. All rights reserved.
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