Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Biomaterials. 2019 Feb;194:84-93. doi: 10.1016/j.biomaterials.2018.12.017. Epub 2018 Dec 17.
This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy)) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-CN) for the first time. While exposured to two-photon laser, Ru(bpy) was activated to generate singlet oxygen (O) and Fe-CN was triggered to split water for oxygen supply in the mean time. Owing to the injection of photoinduced electrons from excited Ru(bpy) to Fe-CN, O generation by Fe-CN was significantly accelerated. After accumulation of the nanocomposite by enhanced permeability and retention (EPR) effect, FCRH was demonstrated to alleviate the tumorous hypoxia and consequently enhance the antitumor efficacy of PDT. Furthermore, tumor metabolism evaluations explained the capability of the nanocomposite in reducing intratumoral hypoxia. Our results provide a new diagram for ameliorating the hypoxic tumor microenvironment and accelerating O generation under two-photon excitation, which will find great potential for spatiotemporally controlled tumor treatment in vivo.
本文报道了一种双光子激发的纳米复合材料 FCRH，以克服肿瘤缺氧，增强光动力疗法（PDT）。通过钌（Ⅱ）配合物（Ru(bpy))和具有聚乙二醇支链的超支化共轭聚合物（HOP）的修饰，首次可以通过铁掺杂碳氮化物（Fe-CN）的双光子照射触发水分解介导的 O 生成。在双光子激光照射下，Ru(bpy)被激活生成单线态氧（O），同时 Fe-CN 被触发分解水以提供氧气供应。由于从激发的 Ru(bpy)向 Fe-CN 注入光致电子，Fe-CN 的 O 生成显著加速。纳米复合材料通过增强的渗透性和保留（EPR）效应积累后，FCRH 被证明可以减轻肿瘤缺氧，并因此增强 PDT 的抗肿瘤疗效。此外，肿瘤代谢评估解释了该纳米复合材料降低肿瘤内缺氧的能力。我们的结果为改善缺氧肿瘤微环境和加速双光子激发下的 O 生成提供了一个新的方案，这将为体内时空控制的肿瘤治疗提供巨大潜力。
