한빛사 논문
Amit Sharma,†,⊥ Min-Goo Lee,‡,⊥ Miae Won,† Seyoung Koo,† Jonathan F. Arambula,∥ Jonathan L. Sessler,*,§,∥ Sung-Gil Chi,*,‡ and Jong Seung Kim,*,†
† Department of Chemistry, Korea University, Seoul 02841 Korea
‡ Department of Life Sciences, Korea University, Seoul 02841, Korea
§ Institute for Supramolecular Chemistry and Catalysis, Shanghai University, Shanghai 200444, China
∥ Department of Chemistry, University of Texas at Austin, Austin, Texas 78712-1224, United States
*Corresponding Authors
Author Contributions
⊥A.S. and M.-G.L. contributed equally.
Abstract
Reported here is a molecular construct (K1) designed to overcome hurdles associated with delivering active drugs to heterogeneous tumor environments. Construct K1 relies on two cancer environment triggers (GSH and H2O2) to induce prodrug activation. It releases an active drug form (SN-38) under conditions of both oxidative and reductive stress in vitro. Specific uptake of K1 in COX-2 positive aggressive colon cancer cells (SW620 and LoVo) was seen, along with enhanced anticancer activity compared with the control agent SN-38. These findings are attributed to environmentally triggered drug release, as well as simultaneous scavenging of species giving rise to intracellular redox stress. K1 serves to downregulate various cancer survival signaling pathways (AKT, p38, IL-6, VEGF, and TNF-α) and upregulate an anti-inflammatory response (IL-10). Compared with SN-38 and DMSO as controls, K1 also displayed an improved in vivo therapeutic efficacy in a xenograft tumor regrowth model with no noticeable systematic toxicity at the administrated dose. We believe that the strategy described here presents an attractive approach to addressing solid tumors characterized by intratumoral heterogeneity.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기