參賽序號:45
海報主題
使用玻尿酸與二硫化物交聯形成的奈米膠增強阿黴素對CD44+癌細胞的遞送
系級
化工系
指導老師及參賽學生
指導老師:詹正雄、陳宇楓
參賽學生:羅翊瑄
構想說明
This study proposes a practical strategy for targeted chemotherapy using biocompatible nanogels (NGs). Hyaluronic acid (HA) was first modified with aldehyde groups (HA-CHO). Then, via emulsification, HA-CHO was crosslinked with either pitaya-derived DNA or a hydrophobic cleavable linker (4,4'-dithiodianiline, DTD) to form doxorubicin (DOX)-loaded NGs (DOX/HA-CHO-DNA and DOX/HA-CHO-DTD). In a separate approach, pre-modified DNA with aldehydes (DNA-CHO) was crosslinked with similar components, resulting in DOX/DNA-CHO-DNA and DOX/DNA-CHO-DTD NGs. DNA in both NG types enhance DOX loading by intercalation between its base pairs. DTD serves as a GSH-responsive linker, cleaved by the high glutathione (GSH) levels in cancer cells. Upon reaching tumors, HA targets CD44-overexpressing cancer organoids, and GSH cleaves DTD, releasing DOX. Compared to free DOX or DOX-loaded NGs with non-cleavable linkers, DOX/HA-CHO-DTD NGs showed superior uptake by cancer cells and organoids. This enhanced uptake triggered apoptosis, evident by 4’,6-diamidino-2-phenylindole (DAPI)-stained condensed DNA and poly ADP-ribose polymerase (PARP) expression This study confirms the efficacy of HA-based nanogels with cleavable linkers in delivering chemotherapeutics specifically to cancer tissues, resulting in selective cytotoxicity.