Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery
| Autor: | Li-Fong Seet, Zhu Li Yap, Tina T. Wong, Stephanie Chu, Hiok Hong Chan, Yong Yao Chun, Timothy Thatt Yang Tan, Li Zhen Toh, Ying Shi Lee |
|---|---|
| Přispěvatelé: | School of Chemical and Biomedical Engineering, School of Materials Science and Engineering |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Small interfering RNA 02 engineering and technology Gelatin Conjunctival Diseases Mice Drug Delivery Systems Osteonectin RNA Small Interfering Internalization Cells Cultured media_common Multidisciplinary Chemistry Chemical engineering [Engineering] Hydrogels 021001 nanoscience & nanotechnology Medicine Female Rabbits 0210 nano-technology Biomedical engineering food.ingredient Biocompatibility media_common.quotation_subject Science Biomedical Engineering Article 03 medical and health sciences Cicatrix food In vivo Gene silencing Animals Humans Gene Silencing technology industry and agriculture Glaucoma Fibroblasts Fibrosis In vitro Mice Inbred C57BL 030104 developmental biology Filtration surgery Drug delivery Biophysics Drug Delivery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Small interfering RNA (siRNA) therapy is a promising epigenetic silencing strategy. However, its widespread adoption has been severely impeded by its ineffective delivery into the cellular environment. Here, a biocompatible injectable gelatin-based hydrogel with positive-charge tuned surface charge is presented as an effective platform for siRNA protection and delivery. We demonstrate a two-step synthesis of a gelatin-tyramine (Gtn-Tyr) hydrogel with simultaneous charge tunability and crosslinking ability. We discuss how different physiochemical properties of the hydrogel interact with siSPARC (siRNA for secreted protein, acidic and rich in cysteine), and study the positive-charge tuned gelatin hydrogel as an effective delivery platform for siSPARC in anti-fibrotic treatment. Through in vitro studies using mouse tenon fibroblasts, the positive-charge tuned Gtn-Tyr hydrogel shows sustained siSPARC cellular internalization and effective SPARC silencing with excellent biocompatibility. Similarly, the same hydrogel platform delivering siSPARC in an in vivo assessment employing a rabbit model shows an effective reduction in subconjunctival scarring in post glaucoma filtration surgery, and is non-cytotoxic compared to a commonly used anti-scarring agent, mitomycin-C. Overall, the current siRNA delivery strategy involving the positive-charge tuned gelatin hydrogel shows effective delivery of gene silencing siSPARC for anti-fibrotic treatment. The current charge tunable hydrogel delivery system is simple to fabricate and highly scalable. We believe this delivery platform has strong translational potential for effective siRNA delivery and epigenetic silencing therapy. Ministry of Education (MOE) Nanyang Technological University National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This research was supported by an NTU internal grant (M4081851), Singapore Ministry of Education NTUitive Gap Fund (NGF-2019-07-004) and the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Programme (NMRC/TCR/008-SERI/2013). Animal studies were partially funded by the SERI core grant (NMRC/CG/015/2013). We would also like to acknowledge Nyein Chan Lwin from SingHealth Experimental Medicine Centre (SEMC), Singapore for assisting the in vivo studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|