Cargando…

Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models

Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, and kill adenocarcinoma cells with the added benefit of re-sensitising...

Descripción completa

Detalles Bibliográficos
Autores principales: Man, Yang Kee Stella, Aguirre-Hernandez, Carmen, Fernandez, Adrian, Martin-Duque, Pilar, González-Pastor, Rebeca, Halldén, Gunnel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408166/
https://www.ncbi.nlm.nih.gov/pubmed/36012152
http://dx.doi.org/10.3390/ijms23168884
_version_ 1784774540920881152
author Man, Yang Kee Stella
Aguirre-Hernandez, Carmen
Fernandez, Adrian
Martin-Duque, Pilar
González-Pastor, Rebeca
Halldén, Gunnel
author_facet Man, Yang Kee Stella
Aguirre-Hernandez, Carmen
Fernandez, Adrian
Martin-Duque, Pilar
González-Pastor, Rebeca
Halldén, Gunnel
author_sort Man, Yang Kee Stella
collection PubMed
description Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, and kill adenocarcinoma cells with the added benefit of re-sensitising drug-resistant cells in preclinical models. Further modifications are required to enable systemic delivery in patients due to the rapid hepatic elimination and neutralisation by blood factors and antibodies. Here, we show data that support the use of coating OAds with gold nanoparticles (AuNPs) as a possible new method of virus modification to help augment tumour uptake. The pre-incubation of cationic AuNPs with AdΔΔ, Ad-3∆-A20T and wild type adenovirus (Ad5wt) was performed prior to infection of prostate/pancreatic cancer cell lines (22Rv, PC3, Panc04.03, PT45) and a pancreatic stellate cell line (PS1). Levels of viral infection, replication and cell viability were quantified 24–72 h post-infection in the presence and absence of AuNPs. Viral spread was assessed in organotypic cultures. The presence of AuNPs significantly increased the uptake of Ad∆∆, Ad-3∆-A20T and Ad5wt in all the cell lines tested (ranging from 1.5-fold to 40-fold), compared to virus alone, with the greatest uptake observed in PS1, a usually adenovirus-resistant cell line. Pre-coating the AdΔΔ and Ad-3∆-A20T with AuNPs also increased viral replication, leading to enhanced cell killing, with maximal effect in the most virus-insensitive cells (from 1.4-fold to 5-fold). To conclude, the electrostatic association of virus with cationic agents provides a new avenue to increase the dose in tumour lesions and potentially protect the virus from detrimental blood factor binding. Such an approach warrants further investigation for clinical translation.
format Online
Article
Text
id pubmed-9408166
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94081662022-08-26 Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models Man, Yang Kee Stella Aguirre-Hernandez, Carmen Fernandez, Adrian Martin-Duque, Pilar González-Pastor, Rebeca Halldén, Gunnel Int J Mol Sci Article Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, and kill adenocarcinoma cells with the added benefit of re-sensitising drug-resistant cells in preclinical models. Further modifications are required to enable systemic delivery in patients due to the rapid hepatic elimination and neutralisation by blood factors and antibodies. Here, we show data that support the use of coating OAds with gold nanoparticles (AuNPs) as a possible new method of virus modification to help augment tumour uptake. The pre-incubation of cationic AuNPs with AdΔΔ, Ad-3∆-A20T and wild type adenovirus (Ad5wt) was performed prior to infection of prostate/pancreatic cancer cell lines (22Rv, PC3, Panc04.03, PT45) and a pancreatic stellate cell line (PS1). Levels of viral infection, replication and cell viability were quantified 24–72 h post-infection in the presence and absence of AuNPs. Viral spread was assessed in organotypic cultures. The presence of AuNPs significantly increased the uptake of Ad∆∆, Ad-3∆-A20T and Ad5wt in all the cell lines tested (ranging from 1.5-fold to 40-fold), compared to virus alone, with the greatest uptake observed in PS1, a usually adenovirus-resistant cell line. Pre-coating the AdΔΔ and Ad-3∆-A20T with AuNPs also increased viral replication, leading to enhanced cell killing, with maximal effect in the most virus-insensitive cells (from 1.4-fold to 5-fold). To conclude, the electrostatic association of virus with cationic agents provides a new avenue to increase the dose in tumour lesions and potentially protect the virus from detrimental blood factor binding. Such an approach warrants further investigation for clinical translation. MDPI 2022-08-10 /pmc/articles/PMC9408166/ /pubmed/36012152 http://dx.doi.org/10.3390/ijms23168884 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Man, Yang Kee Stella
Aguirre-Hernandez, Carmen
Fernandez, Adrian
Martin-Duque, Pilar
González-Pastor, Rebeca
Halldén, Gunnel
Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
title Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
title_full Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
title_fullStr Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
title_full_unstemmed Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
title_short Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
title_sort complexing the oncolytic adenoviruses ad∆∆ and ad-3∆-a20t with cationic nanoparticles enhances viral infection and spread in prostate and pancreatic cancer models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408166/
https://www.ncbi.nlm.nih.gov/pubmed/36012152
http://dx.doi.org/10.3390/ijms23168884
work_keys_str_mv AT manyangkeestella complexingtheoncolyticadenovirusesadandad3a20twithcationicnanoparticlesenhancesviralinfectionandspreadinprostateandpancreaticcancermodels
AT aguirrehernandezcarmen complexingtheoncolyticadenovirusesadandad3a20twithcationicnanoparticlesenhancesviralinfectionandspreadinprostateandpancreaticcancermodels
AT fernandezadrian complexingtheoncolyticadenovirusesadandad3a20twithcationicnanoparticlesenhancesviralinfectionandspreadinprostateandpancreaticcancermodels
AT martinduquepilar complexingtheoncolyticadenovirusesadandad3a20twithcationicnanoparticlesenhancesviralinfectionandspreadinprostateandpancreaticcancermodels
AT gonzalezpastorrebeca complexingtheoncolyticadenovirusesadandad3a20twithcationicnanoparticlesenhancesviralinfectionandspreadinprostateandpancreaticcancermodels
AT halldengunnel complexingtheoncolyticadenovirusesadandad3a20twithcationicnanoparticlesenhancesviralinfectionandspreadinprostateandpancreaticcancermodels