Polymeric nanoparticles for dual-targeted theranostic gene delivery to hepatocellular carcinoma.

Autor: Vaughan HJ; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Zamboni CG; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; 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.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Radant NP; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Jacob D; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA., Mease RC; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, 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.; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA., Tzeng SY; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Gabrielson KL; Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Bhardwaj P; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Guo X; Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Francisco D; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 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.; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.; Department of Materials Science and Engineering and the Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA., Green JJ; Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Department of Materials Science and Engineering and the Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.; Departments of Neurosurgery, Oncology, Ophthalmology, and Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Jul 22; Vol. 8 (29), pp. eabo6406. Date of Electronic Publication: 2022 Jul 20.
DOI: 10.1126/sciadv.abo6406
Abstrakt: 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- 18 F-fluoro-3-hydroxymethylbutyl)guanine ( 18 F-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.
Databáze: MEDLINE