State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; University of Science and Technology of China, Hefei, 230026, China.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; Key Laboratory of Superlight Materials and Surface Technology Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, China.
Biomaterials. 2020 May;240:119850. doi: 10.1016/j.biomaterials.2020.119850. Epub 2020 Feb 11.
Recently, photodynamic therapy (PDT) has been deemed to be the most promising strategy for cancer treatment. To improve the efficacy for PDT, nanocarriers are expected to target mitochondria that are vulnerable to toxic reactive oxygen species (ROS). Moreover, overcoming tumor hypoxia is also conducive to enhance the PDT efficacy. Upconversion nanoparticles (UCNPs) can convert near infrared (NIR) light to visible light, thus stimulating photosensitizers to effectively produce cytotoxic ROS and achieving a high tissue penetration depth. In this study, a multifunctional nanocarrier UCNPs@G4/Ce6/CAT-CTPP was synthesized by a novel thiol-ene and azide-acetylene click reaction route to connect the original oleic acid ligands and dendrimers. Interestingly, the constructed "hydrophobic and hydrophilic pockets" around one single upconversion nanoparticle can simultaneously load hydrophobic photosensitizer Chlorin e6 (Ce6) and hydrophilic catalase (CTA) for catalytic enhanced PDT activated by NIR laser. Also, the mitochondrial targeting molecules (3-carboxypropyl) triphenylphosphonium bromide (CTPP) were modified outside of the dendrimers to efficiently target mitochondria. Both the catalytic degradation of hydrogen peroxide (HO) by catalase to overcome tumor hypoxia and mitochondrial targeting greatly enhance the efficacy of PDT. More importantly, this system provides a new paradigm for designing inorganic nanocrystal core and dendrimer shell for cargo delivery.
最近，光动力疗法（PDT）被认为是治疗癌症最有前途的策略。为了提高 PDT 的疗效，期望纳米载体能够靶向对毒性活性氧（ROS）敏感的线粒体。此外，克服肿瘤缺氧也有利于增强 PDT 的疗效。上转换纳米粒子（UCNPs）可以将近红外（NIR）光转换为可见光，从而刺激光敏剂有效地产生细胞毒性 ROS，并实现高组织穿透深度。在本研究中，通过一种新的硫醇-烯和叠氮-乙炔点击反应途径，合成了一种多功能纳米载体 UCNPs@G4/Ce6/CAT-CTPP，以连接原始的油酸配体和树枝状大分子。有趣的是，在单个上转换纳米粒子周围构建的“疏水性和亲水性口袋”可以同时负载疏水性光敏剂氯卟啉 e6（Ce6）和亲水性过氧化氢酶（CTA），用于 NIR 激光激活的催化增强 PDT。此外，修饰在树枝状大分子外部的线粒体靶向分子（3-羧丙基）三苯基膦溴化物（CTPP）可有效靶向线粒体。过氧化氢酶对过氧化氢（HO）的催化降解以克服肿瘤缺氧和线粒体靶向大大增强了 PDT 的疗效。更重要的是，该系统为设计用于货物输送的无机纳米晶核和树枝状大分子壳提供了一种新的范例。
