Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 6, Issue -, Pages 2053-2061Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S24344
Keywords
accelerated blood clearance; double smart; cleavable; mPEG-lipid derivates; pH-sensitive liposome
Funding
- Yantai University
- Enterprise state key laboratory, China [2010CB735600]
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Background: The ABC phenomenon is described as a syndrome of accelerated clearance of polyethylene glycol (PEG)-modified liposomes from the bloodstream when repeatedly injected, with their increased accumulation in the liver and spleen. Methods: To clarify this immune response phenomenon, we evaluated a novel modified pH--sensitive liposome with a cleavable double smart PEG-lipid derivative (mPEG-Hz-CHEMS). Results: The ABC phenomenon in mice was brought about by repeated injection of conventional PEG-PE liposomes and was accompanied by a greatly increased uptake in the liver. However, a slight ABC phenomenon was brought about by repeated injection of mPEG-CHEMS liposomes and was accompanied by only a slightly increased uptake in the liver, and repeated injection of mPEG-Hz-CHEMS liposomes did not induce the ABC phenomenon and there was no increase in liver accumulation. This finding indicates that the cleavable mPEG-Hz-CHEMS derivative could lessen or eliminate the ABC phenomenon induced by repeated injection of PEGylated liposomes. Conclusion: This research has shed some light on a solution to the ABC phenomenon using a cleavable PEG-Hz-CHEMS derivative encapsulated in nanoparticles.
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