Your browser doesn't support javascript.
loading
Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming.
Hu, Yizong; Tzeng, Stephany Y; Cheng, Leonardo; Lin, Jinghan; Villabona-Rueda, Andres; Yu, Shuai; Li, Sixuan; Schneiderman, Zachary; Zhu, Yining; Ma, Jingyao; Wilson, David R; Shannon, Sydney R; Warren, Tiarra; Rui, Yuan; Qiu, Chenhu; Kavanagh, Erin W; Luly, Kathryn M; Zhang, Yicheng; Korinetz, Nicole; D'Alessio, Franco R; Wang, Tza-Huei; Kokkoli, Efrosini; Reddy, Sashank K; Luijten, Erik; Green, Jordan J; Mao, Hai-Quan.
Afiliação
  • Hu Y; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
  • Tzeng SY; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Cheng L; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
  • Lin J; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Villabona-Rueda A; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
  • Yu S; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
  • Li S; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Schneiderman Z; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
  • Zhu Y; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
  • Ma J; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
  • Wilson DR; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.
  • Shannon SR; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Warren T; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208.
  • Rui Y; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
  • Qiu C; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218.
  • Kavanagh EW; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
  • Luly KM; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.
  • Zhang Y; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
  • Korinetz N; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • D'Alessio FR; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
  • Wang TH; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
  • Kokkoli E; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
  • Reddy SK; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.
  • Luijten E; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Green JJ; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
  • Mao HQ; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A ; 121(35): e2400194121, 2024 Aug 27.
Article em En | MEDLINE | ID: mdl-39172792
ABSTRACT
Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces. Specifically, our strategy permits controlled assembly of small poly(ß-amino ester)/messenger ribonucleic acid (mRNA) nanoparticles into particles with a size that is kinetically tunable between 200 and 1,000 nm with high colloidal stability in physiological media. We found that assembled particles with an average size of 400 nm safely and most efficiently transfect monocytes following intravenous administration and mediate their differentiation into macrophages in the periphery. When a CpG adjuvant is co-loaded into the particles with an antigen mRNA, the monocytes differentiate into inflammatory dendritic cells and prime adaptive anticancer immunity in the tumor-draining lymph node. This platform technology offers a unique ligand-independent, particle-size-mediated strategy for preferential mRNA delivery and enables therapeutic paradigms via monocyte programming.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Monócitos / Nanopartículas Limite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Monócitos / Nanopartículas Limite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2024 Tipo de documento: Article