期刊
JOURNAL OF CONTROLLED RELEASE
卷 250, 期 -, 页码 20-26出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.01.040
关键词
Anti-PEG IgM; ABC phenomenon; Ganglioside; PEGylated liposomes; Splenic B cells
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan [15H04639]
- Grants-in-Aid for Scientific Research [15H04639] Funding Source: KAKEN
Despite the clinical introduction of a vast number of polyethylene glycol (PEG)-conjugated therapeutics, conjugated PEG is also known for an unfortunate inclination toward immunogenicity. Immunogenicity of PEG, manifested by the robust production of anti-PEG IgM, is known to compromise the therapeutic efficacy and/or reduce the tolerance of PEGylated therapeutics. In the present study, we inserted ganglioside into the membrane of PEGylated liposome (PL) to prepare ganglioside-modified PEGylated liposomes (G-PL), and investigated its efficacy in attenuating the anti-PEG IgM response against PL. A single intravenous injection of G-PL significantly attenuated the anti-PEG IgM production, compared with that of naive PL. In addition, pretreatment with G-PL substantially alleviated the anti-PEG IgM response elicited by a subsequent dose of PL, presumably via inducing B cell tolerance, and as a consequence, this modification abrogated/attenuated the incidence of the rapid clearance of subsequently administrated PL. These results indicate that incorporating gangliosides in PEGylated liposome membrane not only prevents the immunogenicity of PEG but also induces the tolerance of B cells to subsequent doses of the immunogenic PL. Consequently, liposomal membrane modification with ganglioside might represent a promising approach to attenuating the immunogenicity of PEGylated liposomes while preserving their therapeutic efficacy, particularly upon repeated administration. (C) 2017 Elsevier B.V. All rights reserved.
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