Single-component self-assembled RNAi nanoparticles functionalized with tumor-targeting iNGR delivering abundant siRNA for efficient glioma therapy |
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| Affiliation: | 1. Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China;2. State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China;1. Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China;2. Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China;3. Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China;1. Department of Prosthodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Engineering Research Center of Technology and Materials for Oral Reconstruction, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China;2. Bioengineering, Don State Technical University, Rostov-on-Don, Russia;3. Institute of Stomatological Research, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China;1. Department of Microbiology and Immunology, Peter Doherty Institute for Infection & Immunity, The University of Melbourne, Parkville 3010, Australia;2. Faculty of Science, Swinburne University of Technology, Hawthorn 3122, Australia;1. Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA;2. Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD, USA;3. College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA;4. Methodology and Data Analysis Center, Sanford Research, Sioux Falls, SD, USA;5. Department of Pharmaceutical Sciences and Plough Center for Sterile Drug Delivery Systems, University of Tennessee Health Science Center, Memphis, TN, USA;6. Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA;7. Department of Pathology, University of Tennessee at Memphis, Memphis, TN, USA;8. Saraswati Dental College, Lucknow, Uttar Pradesh, India;9. Department of Chemistry & Biochemistry, South Dakota State University, Brookings, SD, 57007, USA;1. Department of Biomaterials Science and Technology, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede 7500AE, The Netherlands;2. Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands;3. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands;4. Cancer Centre Karolinska, Karolinska Institutet, Stockholm SE-171 76, Sweden;1. Department of Chemistry of College of Staten Island and The Graduate Center, The City University of New York, Staten Island, NY 10314, USA;2. Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA;3. Department of Biology of College of Staten Island, The City University of New York, Staten Island, NY 10314, USA |
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| Abstract: | Existing limitations of common RNA interference (RNAi) oncotherapy severely compromised their therapeutic effects. In this study, a novel glioma-targeting RNAi system was developed. Single-component RNAi nanospheres were tactfully self-assembled in vitro, combining the carrier and cargo as a whole. An artificially synthesized polycation (pOEI) with redox-sensitive disulfides in structure condensed the RNAi nanospheres into more compacted nanoparticles. Then a novelly designed tumor-homing and penetrating cyclopeptide iNGR was further modified on the surface. iNGR modified RNAi nanoparticles demonstrated significantly enhanced accumulation in glioma site, remaining stable in circulation until the release of naked RNAi nanospheres were triggered off by the paranormal concentration of glutathione within glioma cells. Naked RNAi nanospheres were digested into abudant siRNA afterwards. Remarkable luciferase gene down-regulations have confirmed their outstanding RNAi effects. With specific design of sequences, the iNGR modified RNAi nanoparticles were supposed to be of great potential in safe and efficient glioma therapy in future. |
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| Keywords: | Self-assembled nanoparticle RNAi Tumor-homing and penetrating iNGR Glutathione triggered Glioma therapy |
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