title: Dual targeted immunotherapy viain vivodelivery of biohybrid RNAi-peptide nanoparticles to tumour-associated macrophages and cancer cells.
abstract: Lung cancer is associated with very poor prognosis and considered one of the leading causes of death worldwide. Here, we present highly potent and selective bio-hybrid RNAi-peptide nanoparticles that can induce specific and long-lasting gene therapy in inflammatory tumour associated macrophages (TAMs), via an immune modulation of the tumour milieu combined with tumour suppressor effects. Our data prove that passive gene silencing can be achieved in cancer cells using regular RNAi NPs. When combined with M2 peptide-based targeted immunotherapy that immuno-modulates TAMs cell-population, a synergistic effect and long-lived tumour eradication can be observed along with increased mice survival. Treatment with low doses of siRNA (ED500.0025-0.01 mg/kg) in a multi and long-term dosing system substantially reduced the recruitment of inflammatory TAMs in lung tumour tissue, reduced tumour size (∼95%) and increased animal survival (∼75%) in mice. Our results suggest that it is likely that the combination of silencing important genes in tumour cells and in their supporting immune cells in the tumour microenvironment, such as TAMs, will greatly improve cancer clinical outcomes.
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts, USA; School of Engineering and Materials Science, Queen Mary University of London, London, UK.
authors.forename: João
authors.initials: J
authors.lastname: Conde
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory of Thin Film and Micro/Nano Fabrication Technology of Ministry of Education, School of Electronic Information and Electronical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, P.R.China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Bao
authors.affiliation: Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin, Ireland.
authors.forename: Yeqi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory of Thin Film and Micro/Nano Fabrication Technology of Ministry of Education, School of Electronic Information and Electronical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, P.R.China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
authors.affiliation: School of Engineering and Materials Science, Queen Mary University of London, London, UK.
authors.forename: Helena S
authors.initials: HS
authors.lastname: Azevedo
authors.affiliation: Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin, Ireland.
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Byrne
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts, USA; Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Artzi
authors.affiliation: Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin, Ireland.
authors.forename: Furong
authors.initials: F
authors.lastname: Tian
keywords: RNAi; lung cancer; nanoparticles; tumour targeting; tumour-associated macrophages