In Situ Targeting RGD-Modified Cyclodextrin Inclusion Complex/Hydrogel Hybrid System for Enhanced Glioblastoma Therapy

In Situ Targeting RGD-Modified Cyclodextrin Inclusion Complex/Hydrogel Hybrid System for Enhanced Glioblastoma Therapy

<b>Background/Objectives</b>: Glioblastoma (GBM) remains the most aggressive primary brain tumor, characterized by high malignancy, recurrence rate, and dismal prognosis, thereby demanding innovative therapeutic strategies. In this study, we report a novel in situ targeting inclusion com...

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Main Authors: Xiaofeng Yuan, Zhenhua Wang, Pengcheng Qiu, Zhenhua Tong, Bingwen Wang, Yingjian Sun, Xue Sun, Lu Sui, Haiqiang Jia, Jiajun Wang, Haifeng Tang, Weiliang Ye
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Pharmaceutics
Subjects:
doxorubicin
cyclodextrin
inclusion complex
hydrogel
glioblastoma
Online Access:https://www.mdpi.com/1999-4923/17/7/938
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Summary:<b>Background/Objectives</b>: Glioblastoma (GBM) remains the most aggressive primary brain tumor, characterized by high malignancy, recurrence rate, and dismal prognosis, thereby demanding innovative therapeutic strategies. In this study, we report a novel in situ targeting inclusion complex hydrogel hybrid system (DOX/RGD-CD@Gel) that integrates doxorubicin (DOX) with RGD-conjugated cyclodextrin (RGD-CD) and a thermosensitive hydrogel for enhanced GBM therapy. <b>Methods</b>: The DOX/RGD-CD@Gel system was prepared by conjugating doxorubicin (DOX) with RGD-modified cyclodextrin (RGD-CD) and embedding it into a thermosensitive hydrogel. The drug delivery and antitumor efficacy of this system were evaluated in vitro and in vivo. <b>Results</b>: In vitro and in vivo evaluations demonstrated that DOX/RGD-CD@Gel significantly enhanced cytotoxicity compared to free DOX or DOX/CD formulations. The targeted delivery system effectively promoted apoptosis and inhibited cell proliferation and metastasis in GBM cells. Moreover, the hydrogel-based system exhibited prolonged drug retention in the brain, as evidenced by its temperature- and pH-responsive release characteristics. In a GBM mouse model, DOX/RGD-CD@Gel significantly suppressed tumor growth and improved survival rates. <b>Conclusions</b>: This study presents a paradigm of integrating a targeted inclusion complex with a thermosensitive hydrogel, offering a safe and efficacious strategy for localized GBM therapy with potential translational value.
ISSN:1999-4923

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