Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China.
Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China.
J Photochem Photobiol B. 2021 Sep;222:112274. doi: 10.1016/j.jphotobiol.2021.112274. Epub 2021 Jul 25.
Photodynamic therapy (PDT) has gained much attention in tumor therapy because of its special advantages. PDT heavily depends on the oxygen, yet the tumor microenvironment (TME) is a hypoxic and acid milieu, which weakens the PDT effect. Based on the consideration that the TME deteriorated by the PDT oxygen consumption could activate the hypoxic-sensitive small-molecule drug, we designed and prepared an integrated nanocomposite including zirconium ion metal organic framework (carrier), pyropheophorbide-a (PPa, photosensitizer), and 6-amino flavone (AF, hypoxic-sensitive drug), aiming to exert a cascaded PDT-chemotherapy (CT) antitumor effect and to solve the hypoxic challenge. The prepared nanocomposite showed great stability under the physiological (pH 7.4) condition and could continuously release PPa and AF under slightly acidic pH condition (pH 6.4), suggesting a tumor microenvironment responsive feature. Systematical in vitro and in vivo researches under various conditions (light, dark, hypoxic and normoxic) have showed that the obtained Zr-MOF@PPa/AF@PEG nanoparticles (NPs) had good biocompatibility and could achieve efficient antitumor effects based on PDT- chemotherapy (CT) cascade process. Finally, bright red fluorescence was observed in the tumor cells after internalization implying an application potential in tumor imaging.
光动力疗法（PDT）因其特殊优势在肿瘤治疗中受到广泛关注。PDT 严重依赖氧气，然而肿瘤微环境（TME）是一个缺氧和酸性的环境，这削弱了 PDT 的效果。基于 PDT 氧消耗使 TME 恶化可以激活缺氧敏感的小分子药物这一考虑，我们设计并制备了一种包括锆离子金属有机骨架（载体）、叶啉-a（PPa，光敏剂）和 6-氨基黄酮（AF，缺氧敏感药物）的集成纳米复合材料，旨在发挥级联 PDT-化疗（CT）抗肿瘤作用，并解决缺氧挑战。该纳米复合材料在生理条件（pH 7.4）下表现出良好的稳定性，并在略酸性 pH 条件（pH 6.4）下持续释放 PPa 和 AF，表明具有肿瘤微环境响应特性。在各种条件（光照、黑暗、缺氧和常氧）下进行的系统体外和体内研究表明，所获得的 Zr-MOF@PPa/AF@PEG 纳米粒子（NPs）具有良好的生物相容性，并能够基于 PDT-CT 级联过程实现高效的抗肿瘤效果。最后，在摄取后肿瘤细胞中观察到明亮的红色荧光，这表明其在肿瘤成像中有应用潜力。
