Fu Yang, Ge Yuanxin, Yi Shixiong, Peng Qifeng, Jiang Heng, Zhou Jie
Department of Rehabilitation, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China.
Discov Oncol. 2025 Jul 21;16(1):1382. doi: 10.1007/s12672-025-03079-w.
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.
白藜芦醇(RSV)是一种具有多方面抗癌机制的天然多酚,但面临着显著的药代动力学挑战,这限制了其临床应用。本综述探讨了RSV与水凝胶递送系统的协同整合,以克服这些限制并提高癌症治疗的疗效。水凝胶以其可调节的物理化学性质和刺激响应行为而闻名,能够对RSV的释放进行精确的时空控制,提高稳定性、生物利用度和肿瘤靶向递送。与其他递送系统(如脂质体、聚合物纳米颗粒)相比,负载RSV的水凝胶在持续局部释放和微环境调节方面具有明显优势。先进的水凝胶设计,包括pH和温度响应系统、纳米复合材料和自愈网络,通过维持治疗浓度、调节肿瘤微环境以及与化学光热或免疫治疗策略协同作用,进一步增强了RSV的生物活性。在结直肠癌和胶质母细胞瘤中的临床前应用表明,RSV-水凝胶平台能够通过抑制Wnt/β-连环蛋白和ROS触发的药物激活等机制来抑制转移、逆转化疗耐药性并根除癌症干细胞。虽然这些临床前结果很有前景,但仍存在重大的转化挑战,包括可扩展制造、生物相容性和临床转化。未来的研究重点包括开发更复杂的刺激响应系统,以及探索与新兴治疗方式的潜在协同作用,以缩小向临床应用转化的差距。
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