Gulfam Muhammad, Jo Sung-Han, Vu Trung Thang, Ali Israr, Rizwan Ali, Joo Soo-Bin, Park Sang-Hyug, Lim Kwon Taek
Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, Republic of Korea.
Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, Republic of Korea.
Carbohydr Polym. 2023 Mar 1;303:120457. doi: 10.1016/j.carbpol.2022.120457. Epub 2022 Dec 14.
In this work, bioorthogonal and photodegradable hydrogels derived from norbornene (Nb) functionalized hyaluronic acid and a water soluble coumarin-based cross-linker possessing terminal tetrazine (Tz) groups, were developed for NIR-responsive release of doxorubicin (DOX). The inverse electron demand Diels-Alder cross-linking reaction between Nb and Tz functionalities formed the hydrogels at physiological conditions, whereas N gas liberated during the reaction created pores in the hydrogels. The gelation time ranges (about 5-20 min) and the viscoelastic behavior (G' ~ 346-1380 Pa) demonstrated that the resulting hydrogels were injectable and possessed tunable mechanical properties. Moreover, hydrogels released the encapsulated DOX upon NIR irradiation, owing to the NIR-responsive cleavage of coumarin-ester, and consequently, induced anti-tumor activity in BT-20 cancer cells. Additionally, the hydrogels could be excited at various wavelengths of the visible spectrum and can emit green to red fluorescence, demonstrating their simultaneous photo-responsive drug release and bio-imaging applications.
在这项工作中，我们开发了一种由降冰片烯（Nb）功能化透明质酸和具有末端四嗪（Tz）基团的水溶性香豆素基交联剂衍生而来的生物正交且可光降解的水凝胶，用于近红外响应释放阿霉素（DOX）。Nb和Tz官能团之间的逆电子需求狄尔斯-阿尔德交联反应在生理条件下形成水凝胶，而反应过程中释放的N气在水凝胶中产生孔隙。凝胶化时间范围（约5 - 20分钟）和粘弹性行为（G' ~ 346 - 1380 Pa）表明，所得水凝胶是可注射的，并且具有可调节的机械性能。此外，由于香豆素酯的近红外响应裂解，水凝胶在近红外照射下释放包封的DOX，从而在BT - 约20癌细胞中诱导抗肿瘤活性。此外，水凝胶可以在可见光谱的各种波长下被激发，并能发出绿色到红色的荧光，证明了它们同时具有光响应药物释放和生物成像应用。
