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Peptide-coated graphene oxide nanosheets for prolonged blood circulation
펩타이드 수식 그래핀을 이용한 혈중 지속시간 증강연구

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Authors
박규태
Advisor
오유경
Major
약학대학 약학과
Issue Date
2018-02
Publisher
서울대학교 대학원
Keywords
signal regulatory protein alphaCD47macrophagepeptidegraphene nanosheets
Description
학위논문 (석사)-- 서울대학교 대학원 : 약학대학 약학과, 2018. 2. 오유경.
Abstract
In this study, we modified the surfaces of graphene oxide (GO) nanosheets with a CD47-like signal regulatory protein alpha (SIRPα)-binding peptide (SP). SIRPα is highly expressed in macrophages of the reticuloendothelial system and in tumor-associated macrophages, whereas tumor cells express the surface membrane protein, CD47, which interacts with SIRPα to negatively regulate phagocytosis. The presence of SP on GO nanosheets reduced the macrophage uptake to a greater extent than the PEGylation of such nanosheets. This reduced uptake was found to be mediated by the activation of Src homology region 2 domain-containing phosphatase 1 (SHP-1) and the downstream inhibition of myosin assembly, which is necessary for phagosome formation. Unlike SP-coated GO nanosheets, PEGylated GO nanosheets did not affect myosin assembly or phagocytosis. After in vivo systemic administration, the clearance of SP-coated GO nanosheets was slower than that of PEGylated GO nanosheets, and this difference increased with repeated administration. Finally, SP-coated GO nanosheets showed a higher distribution to tumor tissues than PEGylated GO nanosheets or a physical mixture of SP and GO nanosheets. Our findings indicate that immune-camouflaged GO nanosheets with natural CD47-like SIRPα-binding molecules can reduce the nonspecific loss of such nanosheets through macrophage uptake, thereby enhancing their blood circulation and tumor delivery after multiple injections.
Language
English
URI
https://hdl.handle.net/10371/142231
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Theses (Master's Degree_약학과)
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