Dual Targeted Immunotherapy via In Vivo Delivery of Biohybrid RNAi‐Peptide Nanoparticles to Tumor‐Associated Macrophages and Cancer Cells |
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| Authors: | João Conde Chenchen Bao Yeqi Tan Daxiang Cui Elazer R Edelman Helena S Azevedo Hugh J Byrne Natalie Artzi Furong Tian |
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| Affiliation: | 1. Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard‐MIT Division for Health Sciences and Technology, Cambridge, MA, USA;2. School of Engineering and Materials Science, Queen Mary University of London, London, UK;3. 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;4. Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8, Ireland;5. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;6. Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA |
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| Abstract: | Lung cancer is associated with very poor prognosis and considered one of the leading causes of death worldwide. Here, highly potent and selective biohybrid RNA interference (RNAi)‐peptide nanoparticles (NPs) are presented that can induce specific and long‐lasting gene therapy in inflammatory tumor associated macrophages (TAMs), via an immune modulation of the tumor milieu combined with tumor suppressor effects. The data here 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 tumor eradication can be observed along with increased mice survival. Treatment with low doses of siRNA (ED50 0.0025–0.01 mg kg?1) in a multi and long‐term dosing system substantially reduces the recruitment of inflammatory TAMs in lung tumor tissue, reduces tumor size (≈95%), and increases animal survival (≈75%) in mice. The results here suggest that it is likely that the combination of silencing important genes in tumor cells and in their supporting immune cells in the tumor microenvironment, such as TAMs, will greatly improve cancer clinical outcomes. |
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| Keywords: | lung cancer nanoparticles RNAi tumor‐associated macrophages tumor targeting |
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