Aerosol delivery of star polymer-siRNA nanoparticles as a therapeutic strategy to inhibit lung tumor growth.

Autor: Ma Z; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Australia; School of Women's and Children's Health, UNSW Sydney, Australia; Australian Centre for NanoMedicine, UNSW Sydney, Australia., Wong SW; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Australia., Forgham H; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Australia; School of Women's and Children's Health, UNSW Sydney, Australia; Australian Centre for NanoMedicine, UNSW Sydney, Australia., Esser L; Commonwealth Scientific and Industrial Research Organisation, Melbourne, Australia., Lai M; Drug Delivery Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Australia., Leiske MN; Drug Delivery Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Australia; Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan, Belgium., Kempe K; Drug Delivery Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Australia; Materials Science and Engineering, Monash University, Australia., Sharbeen G; Pancreatic Cancer Translational Research Group, Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Australia; School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Australia., Youkhana J; Pancreatic Cancer Translational Research Group, Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Australia; School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Australia., Mansfeld F; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Australia; Australian Centre for NanoMedicine, UNSW Sydney, Australia; Commonwealth Scientific and Industrial Research Organisation, Melbourne, Australia., Quinn JF; Drug Delivery Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Australia; Department of Chemical Engineering, Faculty of Engineering, Monash University, Australia., Phillips PA; Australian Centre for NanoMedicine, UNSW Sydney, Australia; Pancreatic Cancer Translational Research Group, Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Australia; School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Australia., Davis TP; Drug Delivery Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Australia; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Australia., Kavallaris M; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Australia; School of Women's and Children's Health, UNSW Sydney, Australia; Australian Centre for NanoMedicine, UNSW Sydney, Australia; UNSW RNA Institute, Sydney, UNSW Sydney, Australia. Electronic address: mkavallaris@ccia.org.au., McCarroll JA; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Australia; School of Women's and Children's Health, UNSW Sydney, Australia; Australian Centre for NanoMedicine, UNSW Sydney, Australia; UNSW RNA Institute, Sydney, UNSW Sydney, Australia. Electronic address: jmccarroll@ccia.org.au.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2022 Jun; Vol. 285, pp. 121539. Date of Electronic Publication: 2022 Apr 23.
DOI: 10.1016/j.biomaterials.2022.121539
Abstrakt: Lung cancer is a major contributor to cancer-related death worldwide. siRNA nanomedicines are powerful tools for cancer therapeutics. However, there are challenges to overcome to increase siRNA delivery to solid tumors, including penetration of nanoparticles into a complex microenvironment following systemic delivery while avoiding rapid clearance by the reticuloendothelial system, and limited siRNA release from endosomes once inside the cell. Here we characterized cell uptake, intracellular trafficking, and gene silencing activity of miktoarm star polymer (PDMAEMA-POEGMA) nanoparticles (star nanoparticles) complexed to siRNA in lung cancer cells. We investigated the potential of nebulized star-siRNA nanoparticles to accumulate into orthotopic mouse lung tumors to inhibit expression of two genes [βIII-tubulin, Polo-Like Kinase 1 (PLK1)] which: 1) are upregulated in lung cancer cells; 2) promote tumor growth; and 3) are difficult to inhibit using chemical drugs. Star-siRNA nanoparticles internalized into lung cancer cells and escaped the endo-lysosomal pathway to inhibit target gene expression in lung cancer cells in vitro. Nebulized star-siRNA nanoparticles accumulated into lungs and silenced the expression of βIII-tubulin and PLK1 in mouse lung tumors, delaying aggressive tumor growth. These results demonstrate a proof-of-concept for aerosol delivery of star-siRNA nanoparticles as a novel therapeutic strategy to inhibit lung tumor growth.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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