Aldehyde-Functionalized Cellulose Nanofiber Hydrogels for pH-Sensitive Drug Delivery via Dynamic Imine Bonding
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초록

We designed a hydrogel system that not only responds to disease-relevant pH conditions but also allows precise control over the network density and drug release via acid-catalyzed imine bond formation. By comparing drugs with and without amine functionalities (DOX vs alpha-MS) and evaluating the effect of an acid catalyst on cross-linking and drug diffusion, we provide mechanistic insights into the rational design of cellulose-based smart hydrogels. Drug release experiments revealed pH-dependent behavior with accelerated release under acidic conditions due to imine bond hydrolysis. The presence of an acid catalyst enhanced cross-linking between aldehyde-functionalized TEMPO-oxidized cellulose nanofibers (A-TOCNF) and glycol chitosan (GC), leading to a denser network and suppressing DOX release. SEM analysis showed that acid-catalyzed samples exhibited more compact fibrous structures, correlating with higher mechanical stability, as confirmed by AFM-based Young's modulus measurements. WST-8 assays using Colon26 cells validated the biocompatibility of the drug-free hydrogel and the anticancer efficacy of DOX-loaded hydrogels. Overall, this hydrogel system demonstrates excellent potential as a biodegradable, site-specific drug delivery platform that is responsive to disease-associated pH conditions. Given that over 40% of therapeutic compounds contain amine groups, the platform offers broad applicability for targeted and sustained drug delivery.

키워드

CHITOSAN
제목
Aldehyde-Functionalized Cellulose Nanofiber Hydrogels for pH-Sensitive Drug Delivery via Dynamic Imine Bonding
저자
Tsubota, HiroyaPark, JeongjinKang, HyoungwookKang, DayaeMiura, YamatoSaito, TaikiKono, NanamiKawasaki, RikuJung, Sung HoJung, Jong HwaLee, Ji Ha
DOI
10.1021/acsomega.5c09948
발행일
2026-01
유형
Article; Early Access
저널명
ACS Omega
11
4
페이지
5830 ~ 5838