Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Science advances, 2022-07, Vol.8 (29), p.eabo6406

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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- F-fluoro-3-hydroxymethylbutyl)guanine ( 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.