Zeng Li, Cheng Hui, Dai Yuwei, Su Zhipeng, Wang Chengde, Lei Lei, Lin Deqing, Li Xingyi, Chen Hao, Fan Kelong, Shi Shuai
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
ACS Appl Mater Interfaces. 2021 Jan 13;13(1):233-244. doi: 10.1021/acsami.0c19074. Epub 2020 Dec 29.
Photodynamic therapy (PDT) and photothermal therapies (PTTs) are both promising strategies for effective tumor therapy. However, the absence of O at tumor sites hinders the sustained response of photosensitizers. Here, we develop a recycled cerium oxide (CeO) catalase nanozyme-loaded hyaluronic acid nanovesicle to address the hypoxic tumor microenvironments and targeted delivery of the photosensitizers [indocyanine green (ICG)] to tumors. A polysaccharide complex effectively modifies the surface of a polyethylenimine phenylboronic acid nanostructure to achieve the CeO nanozyme-loading nanovesicles that exhibit both tumor-targeted enhancement and an improved hypoxic microenvironment. Also, the hydrogen peroxide responsiveness and acid-sensitive cleavage of phenylboronic acid specifically disintegrate the ICG/nanozyme coloaded nanovesicles in the tumor microenvironment. The in vitro synergistic tests and tumor suppression rate tests indicated that the cerium oxide nanozyme significantly improves the outcomes of PDT via cerium-element valence state recycling and hypoxia improvement, thus enhancing the tumor suppression efficiency. This pH/HO-responsive nanozyme/ICG codelivery system provides a good carrier model for improving the tumor microenvironment and increasing the efficiency of tumor-targeted PTT and PDT therapies.
光动力疗法（PDT）和光热疗法（PTT）都是有效的肿瘤治疗的有前景的策略。然而，肿瘤部位缺氧阻碍了光敏剂的持续反应。在此，我们开发了一种负载有可循环氧化铈（CeO）过氧化氢酶纳米酶的透明质酸纳米囊泡，以解决肿瘤缺氧微环境问题，并将光敏剂[吲哚菁绿（ICG）]靶向递送至肿瘤。一种多糖复合物有效地修饰了聚乙烯亚胺苯硼酸纳米结构的表面，以实现负载CeO纳米酶的纳米囊泡，其既表现出肿瘤靶向增强作用，又改善了缺氧微环境。此外，过氧化氢响应性和苯硼酸的酸敏裂解作用可在肿瘤微环境中特异性地分解共负载ICG/纳米酶的纳米囊泡。体外协同试验和肿瘤抑制率试验表明，氧化铈纳米酶通过铈元素价态循环和缺氧改善显著提高了PDT的效果，从而提高了肿瘤抑制效率。这种pH/H₂O₂响应性纳米酶/ICG共递送系统为改善肿瘤微环境和提高肿瘤靶向PTT和PDT治疗效率提供了一个良好的载体模型。
