Engineering Multifunctional RNAi Nanomedicine To Concurrently Target Cancer Hallmarks for Combinatorial Therapy |
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| Authors: | Dr Yanlan Liu Xiaoyuan Ji Winnie W L Tong Diana Askhatova Dr Tingyuan Yang Dr Hongwei Cheng Prof Yuzhuo Wang Prof Jinjun Shi |
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| Institution: | 1. Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;2. Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, P. R. China;3. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China;4. Department of Experimental Therapeutics, British Columbia Cancer Agency, Vancouver, BC, Canada |
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| Abstract: | Cancer hallmarks allow the complexity and heterogeneity of tumor biology to be better understood, leading to the discovery of various promising targets for cancer therapy. An amorphous iron oxide nanoparticle (NP)‐based RNAi strategy is developed to co‐target two cancer hallmarks. The NP technology can modulate the glycolysis pathway by silencing MCT4 to induce tumor cell acidosis, and concurrently exacerbate oxidative stress in tumor cells via the Fenton‐like reaction. This strategy has the following features for systemic siRNA delivery: 1) siRNA encapsulation within NPs for improving systemic stability; 2) effective endosomal escape through osmotic pressure and/or endosomal membrane oxidation; 3) small size for enhancing tumor tissue penetration; and 4) triple functions (RNAi, Fenton‐like reaction, and MRI) for combinatorial therapy and in vivo tracking. |
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| Keywords: | cancer hallmarks iron oxide nanoparticles MRI RNAi tumor penetration |
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