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

Hannah J. Vaughan; Camila G. Zamboni; Laboni F. Hassan; Nicholas P. Radant; Desmond Jacob; Ronnie C. Mease; Il Minn; Stephany Y. Tzeng; Kathleen L. Gabrielson; Pranshu Bhardwaj; Xin Guo; David Francisco; Martin G. Pomper; Jordan J. Green

doi:10.1126/sciadv.abo6406

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

Journal article

Peer reviewed

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

Hannah J. Vaughan, Camila G. Zamboni, Laboni F. Hassan, Nicholas P. Radant, Desmond Jacob, Ronnie C. Mease, Il Minn, Stephany Y. Tzeng, Kathleen L. Gabrielson, Pranshu Bhardwaj, …

Science advances, Vol.8(29), p.eabo6406

07/22/2022

DOI: 10.1126/sciadv.abo6406

PMID: 35857843

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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. A nanoparticle platform with multiple levels of cancer-specific targeting was designed to simultaneously kill and image liver tumors.

Applied Sciences and Engineering

Biomedicine and Life Sciences

Cancer

SciAdv r-articles

Details

Title: Subtitle: Polymeric nanoparticles for dual-targeted theranostic gene delivery to hepatocellular carcinoma
Creators: Hannah J. Vaughan - Johns Hopkins University
Camila G. Zamboni - Johns Hopkins University
Laboni F. Hassan - Johns Hopkins University
Nicholas P. Radant - Johns Hopkins University
Desmond Jacob - Johns Hopkins University
Ronnie C. Mease - Johns Hopkins University
Il Minn - Johns Hopkins University
Stephany Y. Tzeng - Johns Hopkins University
Kathleen L. Gabrielson - Johns Hopkins University
Pranshu Bhardwaj - Johns Hopkins University
Xin Guo - Johns Hopkins University
David Francisco - Johns Hopkins University
Martin G. Pomper - Johns Hopkins University
Jordan J. Green - Johns Hopkins University
Resource Type: Journal article
Publication Details: Science advances, Vol.8(29), p.eabo6406
DOI: 10.1126/sciadv.abo6406
PMID: 35857843
ISSN: 2375-2548
eISSN: 2375-2548
Publisher: American Association for the Advancement of Science
Grant note: ; P41EB024495 / ; P41EB028239 / ; F31CA250365 / ; R01EB022148 / ;
Language: English
Date published: 07/22/2022
Academic Unit: Radiology
Record Identifier: 9985179680202771

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