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조회136

부산대학교

Chem. Eng. J., Volume 505, 1 February 2025, 158935 | https://doi.org/10.1016/j.cej.2024.158935 On-site sol-gel-sol transition of alginate enables reversible shielding/deshielding of tumor cell-activated nanoconjugates for precise local colorectal cancer therapy

Juho Lee ^a,b, Jihyun Kim ^a,b, Dongmin Kwak ^a, Hyunwoo Kim^a, Muneeb Ullah ^a, Min Chan Kim ^c, Kyu Hyun ^c, Eun Hee Lee ^d, Hwayoung Yun ^a,b, Yunjin Jung^a,b, Jin-Wook Yoo^a,b

^aCollege of Pharmacy, Pusan National University, Busan 46241, Republic of Korea
^bResearch Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea
^cSchool of Chemical Engineering, Pusan National University, Busan 46241, Republic of Korea
^dCollege of Pharmacy, Korea University, Sejong 30019, Republic of Korea

Corresponding author: Jin-Wook Yoo

Abstract

Although local colorectal cancer (CRC) therapy can be achieved by delivering CRC-targeted nanoparticles directly to the tumor tissues within the colorectal cavity, bypassing systemic circulation through the oral administration route, physical entrapment of the nanoparticles by the small intestinal epithelium, and premature drug loss before reaching the colorectal cavity results in limited local therapeutic efficacy. To overcome these limitations, this study aimed to develop CRC cell-activated nanoconjugates (CTNCs)-in-alginate (Alg/CTNCs). After oral administration, Alg/CTNCs undergo a sol-gel transition upon exposure to gastric acid, and the alginate gel matrix effectively shields the incorporated CTNCs, preventing unwanted interactions with the intestinal epithelium and drug loss before reaching the colorectum. Upon reaching the colorectum, the elevated pH triggers a gel-sol transition in the gelated Alg/CTNCs, and the deshielded CTNCs from the alginate gel matrix show highly CRC-selective accumulation. Finally, drugs are released in response to intracellular esterase, ultimately leading to potent local antitumor effects without systemic side effects. These findings suggest that the reversible shielding/deshielding of nanomaterials during gastrointestinal tract passage, along with intratumoral environment-activated drug release strategies, enables precise local CRC therapy.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-04-07)
연구진국내 연구진
분야 의약학 > 약학

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