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Updated: Jul 30, 2025
Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
Published on: April 15, 2016
Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection
Hannah J Vaughan1,2, Camila G Zamboni1,2, Kathryn M Luly1,2
1Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Purpose:
Hepatocellular carcinoma (HCC) has limited treatment options, and modest survival after systemic chemotherapy or procedures such as transarterial chemoembolization (TACE). There is therefore a need to develop targeted therapies to address HCC. Gene therapies hold immense promise in treating a variety of diseases, including HCC, though delivery remains a critical hurdle. This study investigated a new approach of local delivery of polymeric nanoparticles (NPs) via intra-arterial injection for targeted local gene delivery to HCC tumors in an orthotopic rat liver tumor model.
Methods:
Poly(beta-amino ester) (PBAE) nanoparticles were formulated and assessed for GFP transfection in N1-S1 rat HCC cells in vitro. Optimized PBAE NPs were next administered to rats via intra-arterial injection with and without orthotopic HCC tumors, and both biodistribution and transfection were assessed.
Results:
In vitro transfection of PBAE NPs led to >50% transfected cells in adherent and suspension culture at a variety of doses and weight ratios. Administration of NPs via intra-arterial or intravenous injection demonstrated no transfection of healthy liver, while intra-arterial NP injection led to transfection of tumors in an orthotopic rat HCC model.
Conclusion:
Hepatic artery injection is a promising delivery approach for PBAE NPs and demonstrates increased targeted transfection of HCC tumors compared to intravenous administration, and offers a potential alternative to standard chemotherapies and TACE. This work demonstrates proof of concept for administration of polymeric PBAE nanoparticles via intra-arterial injection for gene delivery in rats.
Insights
This study shows that intra-arterial injection of poly(beta-amino ester) nanoparticles effectively delivers genes to hepatocellular carcinoma (HCC) tumors in rats, offering a promising targeted therapy alternative.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) presents limited therapeutic options with modest survival rates.
- Existing treatments like chemotherapy and transarterial chemoembolization (TACE) have limitations.
- Gene therapy offers potential for HCC treatment, but efficient delivery remains a challenge.
Purpose of the Study:
- To investigate a novel local delivery method for targeted gene therapy in HCC.
- To evaluate the efficacy of polymeric nanoparticles (NPs) delivered via intra-arterial injection for HCC treatment.
- To establish a proof of concept for intra-arterial gene delivery in an orthotopic rat liver tumor model.
Main Methods:
- Poly(beta-amino ester) (PBAE) nanoparticles were formulated and tested for GFP transfection in rat HCC cells in vitro.
- Optimized PBAE NPs were administered to rats with and without orthotopic HCC tumors via intra-arterial injection.
- Biodistribution and gene transfection efficiency were assessed following NP administration.
Main Results:
- In vitro studies showed PBAE NPs achieved >50% transfection in HCC cells.
- Intra-arterial NP injection successfully transfected tumors in an orthotopic rat HCC model.
- Neither intra-arterial nor intravenous NP administration resulted in transfection of healthy liver tissue.
Conclusions:
- Intra-arterial hepatic artery injection is a viable and promising approach for PBAE nanoparticle delivery.
- This method demonstrates targeted transfection of HCC tumors, outperforming intravenous administration.
- This study provides proof of concept for intra-arterial polymeric NP gene delivery as a potential alternative to TACE and chemotherapy.
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