title: Suppressive immune response of poly-(sarcosine) chains in peptide-nanosheets in contrast to polymeric micelles.
abstract: Nanoparticles are expected to be applicable for the theranostics as a carrier of the diagnostic and therapeutic agents. Lactosome is a polymeric micelle composed of amphiphilic polydepsipeptide, poly(sarcosine)64-block-poly(L-lactic acid)30, which was found to accumulate in solid tumors through the enhanced permeability and retention effect. However, lactosome was captured by liver on the second administration to a mouse. This phenomenon is called as the accelerated blood clearance phenomenon. On the other hand, peptide-nanosheet composed of amphiphilic polypeptide, poly(sarcosine)60-block-(L-Leu-Aib)6, where the poly(L-lactic acid) block in lactosome was replaced with the (L-Leu-Aib)6 block, abolished the accelerated blood clearance phenomenon. The ELISA and in vivo near-infrared fluorescence imaging revealed that peptide-nanosheets did not activate the immune system despite the same hydrophilic block being used. The high surface density of poly(sarcosine) chains on the peptide-nanosheet may be one of the causes of the suppressive immune response.
authors.affiliation: Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, 53 Shogoin kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hara
authors.forename: Motoki
authors.initials: M
authors.lastname: Ueda
authors.forename: Cheol Joo
authors.initials: CJ
authors.lastname: Kim
authors.forename: Akira
authors.initials: A
authors.lastname: Makino
authors.forename: Isao
authors.initials: I
authors.lastname: Hara
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ozeki
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Kimura
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D008823:Micelles; D010455:Peptides; C015475:polysarcosine; D012521:Sarcosine
keywords: T-independent antigen; immune response; nanoparticles; nanosheet; polymeric micelle