Hyperbranched cationic polysaccharide derivatives for efficient siRNA delivery and diabetic wound healing enhancement.

Hyperbranched cationic polysaccharide derivatives for efficient siRNA delivery and diabetic wound healing enhancement. Int J Biol Macromol. 2020 Mar 17;: Authors: Lan B, Wu J, Li N, Pan C, Yan L, Yang C, Zhang L, Yang L, Ren M Abstract Gene vectors are important for successful siRNA delivery. Four types of hyperbranched cationic polysaccharide derivatives (HCP) were synthesized by conjuncting 1,2-ethylenediamine (EDA) and diethylenetriamine (DETA) with glycogen or amylopectin respectively and named as G-EDA, G-DETA, A-EDA and A-DETA. The efficiency and safety of these HCPs to deliver siRNA were explored in vitro and in vivo. Our results showed that HCPs could form complexes with siRNA. All HCP/siRNA exhibited negligible cytotoxicity. Compared with A-EDA and A-DETA, G-EDA and G-DETA could carry much more siRNA into cells and then escape from endosomes. The delivery of MMP-9 siRNA (siMMP-9) by G-EDA and G-DETA significantly inhibited MMP-9 in HaCaT cells. Wound models in diabetic rats demonstrated that treatment of G-EDA/siMMP-9 could potently knock down MMP-9 of skin wound tissues and then enhanced wound healing. In summary, this study provided an effective and safe approach for siRNA delivery in vitro and in vivo. PMID: 32198034 [PubMed - as supplied by publisher]
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research