Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection

Hannah J Vaughan; Camila G Zamboni; Kathryn M Luly; Ling Li; Kathleen L Gabrielson; Laboni F Hassan; Nicholas P Radant; Pranshu Bhardwaj; Florin M Selaru; Martin G Pomper; Jordan J Green

doi:10.2147/IJN.S390384

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Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection

Journal article

Open access

Peer reviewed

Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection

Hannah J Vaughan, Camila G Zamboni, Kathryn M Luly, Ling Li, Kathleen L Gabrielson, Laboni F Hassan, Nicholas P Radant, Pranshu Bhardwaj, Florin M Selaru, Martin G Pomper, …

International journal of nanomedicine, Vol.18, pp.2525-2537

01/01/2023

DOI: 10.2147/IJN.S390384

PMID: 37197026

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Abstract

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. 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. 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. 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.

Animals

Carcinoma, Hepatocellular - genetics

Carcinoma, Hepatocellular - therapy

Chemoembolization, Therapeutic - methods

Injections, Intra-Arterial

Liver Neoplasms - genetics

Liver Neoplasms - therapy

Polymers

Rats

Tissue Distribution

Details

Title: Subtitle: Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection
Creators: Hannah J Vaughan - Johns Hopkins University
Camila G Zamboni - Johns Hopkins University
Kathryn M Luly - Johns Hopkins University
Ling Li - Johns Hopkins University
Kathleen L Gabrielson - Johns Hopkins University
Laboni F Hassan - Johns Hopkins University
Nicholas P Radant - Johns Hopkins University
Pranshu Bhardwaj - Johns Hopkins University
Florin M Selaru - Johns Hopkins University
Martin G Pomper - Johns Hopkins University
Jordan J Green - Johns Hopkins University
Resource Type: Journal article
Publication Details: International journal of nanomedicine, Vol.18, pp.2525-2537
DOI: 10.2147/IJN.S390384
PMID: 37197026
NLM abbreviation: Int J Nanomedicine
ISSN: 1178-2013
eISSN: 1178-2013
Language: English
Date published: 01/01/2023
Academic Unit: Radiology
Record Identifier: 9985179849602771

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