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Polymeric nanoparticles for dual-targeted theranostic gene delivery to hepatocellular carcinoma.
Vaughan, Hannah J; Zamboni, Camila G; Hassan, Laboni F; Radant, Nicholas P; Jacob, Desmond; Mease, Ronnie C; Minn, Il; Tzeng, Stephany Y; Gabrielson, Kathleen L; Bhardwaj, Pranshu; Guo, Xin; Francisco, David; Pomper, Martin G; Green, Jordan J.
Afiliação
  • Vaughan HJ; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Zamboni CG; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Hassan LF; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Radant NP; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Jacob D; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Mease RC; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Minn I; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Tzeng SY; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Gabrielson KL; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
  • Bhardwaj P; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
  • Guo X; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Francisco D; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
  • Pomper MG; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Green JJ; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Sci Adv ; 8(29): eabo6406, 2022 07 22.
Article em En | MEDLINE | ID: mdl-35857843
ABSTRACT
Hepatocellular carcinoma (HCC) develops predominantly in the inflammatory environment of a cirrhotic liver caused by hepatitis, toxin exposure, or chronic liver disease. A targeted therapeutic approach is required to enable cancer killing without causing toxicity and liver failure. Poly(beta-amino-ester) (PBAE) nanoparticles (NPs) were used to deliver a completely CpG-free plasmid harboring mutant herpes simplex virus type 1 sr39 thymidine kinase (sr39) DNA to human HCC cells. Transfection with sr39 enables cancer cell killing with the prodrug ganciclovir and accumulation of 9-(4-18F-fluoro-3-hydroxymethylbutyl)guanine (18F-FHBG) for in vivo imaging. Targeting was achieved using a CpG-free human alpha fetoprotein (AFP) promoter (CpGf-AFP-sr39). Expression was restricted to AFP-producing HCC cells, enabling selective transfection of orthotopic HCC xenografts. CpGf-AFP-sr39 NP treatment resulted in 62% reduced tumor size, and therapeutic gene expression was detectable by positron emission tomography (PET). This systemic nanomedicine achieved tumor-specific delivery, therapy, and imaging, representing a promising platform for targeted treatment of HCC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Herpesvirus Humano 1 / Carcinoma Hepatocelular / Nanopartículas / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Sci Adv Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Herpesvirus Humano 1 / Carcinoma Hepatocelular / Nanopartículas / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Sci Adv Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos