Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China; Chongqing Collaborative Innovation Center for Minimally-invasive and Noninvasive Medicine, Chongqing 400016, PR China.
Biomaterials. 2018 Mar;157:107-124. doi: 10.1016/j.biomaterials.2017.12.003. Epub 2017 Dec 9.
The study reports a multifunctional nanoplatform based on mesoporous silica coated gold nanorod (AuNR@MSN) to overcome biological barriers associating with nanocarrier for multiple enhanced photodynamic therapy (PDT) and photothermal therapy (PPT). Indocyanine green (ICG) was loaded into AuNR@MSN and end-capped with β-cyclodextrin (β-CD). Then, a peptide RLA ([RLARLAR]) with plasma membrane permeability and mitochondria-targeting capacity was anchored to AuNR@MSN via host-gust interaction. Subsequently, a charge-reversible polymer was introduced to endow stealth property. When the nanoplatform extravasates to tumor tissue, the weak acidity in tumor microenvironment could induce the dissociation of charge-reversible polymer and re-exposure of RLA peptide. Such a pH-mediated transition could facilitate the targeted accumulation of the nanoplatform in mitochondria. Upon singular 808 nm laser irradiation, the nanoplatform displayed enhanced PDT effect through the generation of reactive oxygen species (ROS) mediated by the local electric field of AuNR, plasmonic photothermal effect, and leakage of endogenous ROS by mitochondrion-targeted PDT. Meanwhile, local hyperthermia was generated by both ICG and AuNR for PPT. The in vitro and in vivo experiments demonstrated that the composite nanoplatform had good antitumor effect with minimal side effect. This work provides new insight into the development of new phototherapeutics for oncotherapy.
该研究报道了一种基于介孔硅包覆金纳米棒（AuNR@MSN）的多功能纳米平台，用于克服与纳米载体相关的生物屏障，实现多种增强的光动力疗法（PDT）和光热疗法（PPT）。吲哚菁绿（ICG）被装载到 AuNR@MSN 中，并通过β-环糊精（β-CD）进行端封。然后，一种具有细胞膜通透性和线粒体靶向能力的肽 RLA（[RLARLAR]）通过主客体相互作用被锚定到 AuNR@MSN 上。随后，引入一种电荷可逆聚合物赋予其隐身特性。当纳米平台渗出到肿瘤组织中时，肿瘤微环境中的弱酸性可以诱导电荷可逆聚合物的解离和 RLA 肽的重新暴露。这种 pH 介导的转变可以促进纳米平台在线粒体中的靶向积累。在 808nm 激光单照射下，纳米平台通过 AuNR 的局部电场介导的活性氧（ROS）生成、等离子体光热效应以及线粒体靶向 PDT 引发的内源性 ROS 泄漏，显示出增强的 PDT 效果。同时，ICG 和 AuNR 均产生局部过热以实现 PPT。体外和体内实验表明，该复合纳米平台具有良好的抗肿瘤效果，副作用极小。这项工作为开发用于肿瘤治疗的新型光疗药物提供了新的思路。
