title: Nanocapsules of therapeutic proteins with enhanced stability and long blood circulation for hyperuricemia management.
abstract: Among a broad spectrum of medical treatments, protein therapeutics holds tremendous opportunities for the treatment of metabolic disorders, cancer, autoimmune diseases and etc. Broad adaption of protein therapeutics, however, still remain challenging, not only because of poor protein stability, but they also experience fast clearance after administrated and elicit immune responses, resulting in undesirable biodistribution and short blood residence time. In this study, we demonstrate a novel protein delivery method via encapsulating therapeutic proteins within thin shells of poly(N-vinylpyrrolidone) (PVP), which leads to significantly improved protein stability, reduced macrophage uptake, prolonged circulation time and reduced immunogenicity. Exemplified with urate oxidase (UOx), the enzyme used for hyperuricemia treatment, as-formed UOx nanocapsules, n(UOx), exhibits enhanced stability, more significant therapeutic effects, and a more than 10-fold improvement in circulation time when compared with native UOx. This technology not only demonstrates the use of UOx nanocapsules for hyperuricemia management, but also provides a general approach for a broad spectrum of therapeutic proteins for in vivo applications.
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Chemical and Bimolecular Engineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Bimolecular Engineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology and Biomedicine and Division of Life and Health Sciences, Tsinghua University, Shenzhen, Guangdong 518055, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Chemical and Bimolecular Engineering, University of California, Los Angeles, CA 90095, USA. Electronic address: luucla@g.ucla.edu.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004355:Drug Stability; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D014357:Trypsin / Q000737:chemistry; D014503:Urate Oxidase / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053769:Nanocapsules; D011760:Pyrrolidinones; D007073:Immunoglobulin E; C042670:N-vinyl-2-pyrrolidinone; D014503:Urate Oxidase; D014357:Trypsin
keywords: Hyperuricemia management; Long circulation; Protein delivery; Protein therapeutics