Fucoidan-based, tumor-activated nanoplatform for overcoming hypoxia and enhancing photodynamic therapy and antitumor immunity
Fucoidan-based, tumor-activated nanoplatform for overcoming hypoxia and enhancing photodynamic therapy and antitumor immunity
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基于褐藻糖胶的肿瘤激活纳米平台，用于克服缺氧和增强光动力疗法和抗肿瘤免疫
DOI：
10.1016/j.biomaterials.2020.120227
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发表时间：
2020-10-01
期刊：
影响因子：
14
通讯作者：
Mi, Fwu-Long
中科院分区：
文献类型：
--
作者：
Chung, Chu-Hung;Lu, Kun-Ying;Mi, Fwu-Long
多功能纳米平台与光动力疗法（PDT）和抗癌药物的结合在癌症治疗中显示出巨大的前景。然而，它们的疗效受到低特异性、低氧水平和耐肿瘤免疫微环境的限制。在此，我们开发了一种生物相容性治疗纳米平台（FM@VP），该平台基于由功能多糖岩藻聚糖和生物可还原聚酰胺胺（PAMAM）树状大分子、光敏剂维托酚芬（VP）和MnO2纳米颗粒（肿瘤微环境响应氧进化纳米材料）组成的纳米复合物共组装成多功能纳米颗粒簇。树突状聚合物-岩藻聚糖多离子纳米复合物（DFPN）特异性靶向p -选择素过表达的三阴性乳腺癌（TNBC）和肿瘤相关血管，并对肿瘤中的谷胱甘肽（GSH）敏感。更重要的是，这种FM@VP纳米复合物同时克服了肿瘤缺氧，抑制了致癌信号，减弱了肿瘤介导的免疫抑制，从而提高了PDT的治疗效果，同时增强了抗肿瘤免疫和抗转移。这一发现为协同癌症靶向/光动力/免疫治疗提供了强有力的策略，并可作为安全的临床转化方法。
Multifunctional nanoplatforms combined with photodynamic therapy (PDT) and anticancer drugs have shown great promising in cancer therapy. However, their efficacy is limited by the low specificity, low oxygen levels, and a tolerant tumor immune microenvironment. Herein, we developed a biocompatible theranostic nanoplatform (FM@VP) based on co-assembly of a nanocomplex formed by a functional polysaccharide fucoidan and a bioreducible polyamidoamine (PAMAM) dendrimer, a photosensitizer verteporfin (VP), and MnO2 nanoparticles (a tumor microenvironment responsive oxygen evolving nanomaterial) into a multifunctional nanoparticle cluster. The dendrimer-fucoidan polyionic nanocomplex (DFPN) specifically targeted P-selectin-overexpressed triple-negative breast cancer (TNBC) and the tumor-associated vasculature, and was sensitive to glutathione (GSH) in tumor. More importantly, this FM@VP nanocomplex simultaneously overcame tumor hypoxia, suppressed oncogenic signaling, and attenuated tumor-mediated immunosuppression, resulting in improving therapeutic efficacy of PDT while enhancing antitumor immunity and anti-metastasis. This discovery provides a powerful strategy for synergetic cancer targeting/photodynamic/immunotherapy and could serve as a safe clinical translational approach.