Yoon, Hong Yeol Kim, Hyun Ryoung Saravanakumar, Gurusamy Heo, Roun Chae, Su Young Um, Wooram Kim, Kwangmeyung Kwon, Ick Chan Lee, Jun Young Lee, Doo Sung Park, Jae Chan Park, Jae Hyung 2024-01-20T11:00:43Z 2024-01-20T11:00:43Z 2021-09-05 2013-12-28 0168-3659 https://pubs.kist.re.kr/handle/201004/127314 The successful clinical translation of siRNA-based therapeutics requires efficient carrier systems that can specifically deliver siRNA within the cytosol of the target cells. Although numerous polymeric nanocarriers forming ionic complexes with siRNA have been investigated for cancer therapy, their poor stability and lack of tumor targetability have impeded their in vivo applications. To surmount these limitations, we synthesized a novel type of biodegradable hyaluronic acid-graft-poly(dimethylaminoethyl methacrylate) (HPD) conjugate that can form complexes with siRNA and be chemically crosslinked via the formation of the disulfide bonds under facile conditions. The crosslinked siRNA-HPD (C-siRNA-HPD) complexes exhibited high stability in a 50% serum solution, as compared to the uncrosslinked siRNA-HPD (U-siRNA-HPD) complexes and free siRNA. Both the C-siRNA-HPD and U-siRNA-HPD complexes were efficiently taken up by the CD44-overexpressing melanoma cells (B16F10), but not by the normal fibroblast cells (NIH3T3). When the RFP-expressing B16F10 cells were treated with the complexes or free siRNA, the C-siRNA-HPD complexes showed the highest decrease in RFP expression. In vivo studies demonstrated the selective accumulation of C-siRNA-HPD complexes at the tumor site after their systemic administration into tumor-bearing mice, resulting in an efficient gene silencing effect. Overall, these results suggest that the HPD conjugate could be used as an efficient carrier for the tumor-targeted delivery of siRNA. (C) 2013 Elsevier B. V. All rights reserved. English ELSEVIER GENE DELIVERY POLY(ETHYLENE GLYCOL) COMPLEX MICELLES VEGF SIRNA POLYPLEXES BIODISTRIBUTION THERAPEUTICS NANOCARRIERS CIRCULATION COPOLYMERS Bioreducible hyaluronic acid conjugates as siRNA carrier for tumor targeting Article 10.1016/j.jconrel.2013.09.008 1 JOURNAL OF CONTROLLED RELEASE, v.172, no.3, pp.653 - 661 JOURNAL OF CONTROLLED RELEASE 172 3 653 661 scie scopus 000328492800007 2-s2.0-84887162804 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article GENE DELIVERY POLY(ETHYLENE GLYCOL) COMPLEX MICELLES VEGF SIRNA POLYPLEXES BIODISTRIBUTION THERAPEUTICS NANOCARRIERS CIRCULATION COPOLYMERS Hyaluronic acid Bioreducible conjugate Stability Tumor targetability siRNA