Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system x c - in liver cancer: A non-ferroptotic approach.

Autor: Yoo SY; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea., Kim HY; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea., Kim DH; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Shim WS; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea., Lee SM; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea., Lee DH; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Koo JM; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Yoo JH; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Koh S; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Park JC; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Yu J; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Jeon JS; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea., Baek MJ; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea., Kim DD; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea; Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea., Lee JY; Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea., Oh SJ; Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea; Department of Pharmacology, College of Medicine, University of Ulsan, Seoul, 05505, Republic of Korea., Kim SK; College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: sangkim@cnu.ac.kr., Lee JY; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea; Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: lee.jy@snu.ac.kr., Kang KW; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: kwkang@snu.ac.kr.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Nov; Vol. 375, pp. 574-588. Date of Electronic Publication: 2024 Sep 22.
DOI: 10.1016/j.jconrel.2024.09.029
Abstrakt: Erastin, a ferroptosis-inducing system x c - inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system x c - .
Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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