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Review
. 2025 Jul 21;16(1):1382.
doi: 10.1007/s12672-025-03079-w.

A review of synergistic strategies in cancer therapy: resveratrol-loaded hydrogels for targeted and multimodal treatment

Yang Fu #  1 , Yuanxin Ge #  2 , Shixiong Yi  1 , Qifeng Peng  1 , Heng Jiang  1 , Jie Zhou  3
Affiliations
Review

A review of synergistic strategies in cancer therapy: resveratrol-loaded hydrogels for targeted and multimodal treatment

Yang Fu et al. Discov Oncol. .

Abstract

Resveratrol (RSV), a natural polyphenol with multifaceted anticancer mechanisms, faces significant pharmacokinetic challenges that limit its clinical utility. This review explores the synergistic integration of RSV with hydrogel-based delivery systems to overcome these limitations and enhance therapeutic efficacy in cancer treatment. Hydrogels, renowned for their tunable physicochemical properties and stimuli-responsive behavior, enable precise spatiotemporal control over RSV release, improving stability, bioavailability, and tumor-targeted delivery. Compared to alternative delivery systems (e.g., liposomes, polymeric nanoparticles), RSV-loaded hydrogels offer distinct advantages in sustained local release and microenvironmental modulation. Advanced hydrogel designs, including pH- and temperature-responsive systems, nanocomposites, and self-healing networks, further amplify RSV's bioactivity by sustaining therapeutic concentrations, modulating tumor microenvironments, and synergizing with chemo-photothermal or immunotherapeutic strategies. Preclinical applications in colorectal cancer and glioblastoma demonstrate RSV-hydrogel platforms' ability to suppress metastasis, reverse chemoresistance, and eradicate cancer stem cells through mechanisms such as Wnt/β-catenin inhibition and ROS-triggered drug activation. While these preclinical results are promising, significant translational challenges remain, including scalable manufacturing, biocompatibility, and clinical translation. Future research priorities include developing more sophisticated stimuli-responsive systems and exploring potential synergies with emerging therapeutic modalities to bridge the gap towards clinical application.

Keywords: Cancer therapy; Chemosensitization; Hydrogels; Multimodal treatment; Nanocomposites; Resveratrol; Targeted drug delivery; Tumor microenvironment.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Stimuli-responsive drug release mechanisms of hydrogels
Fig. 2
Fig. 2
In vivo efficacy of RSV-hydrogel in colorectal cancer models
See this image and copyright information in PMC

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