| Autor: |
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 |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Science advances. 8(29) |
| ISSN: |
2375-2548 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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