CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.
Beijing Key Laboratory of Organic Materials Testing Technology and Quality Evaluation, Beijing Center for Physical and Chemical Analysis, Beijing, 100089, China.
Theranostics. 2020 Jun 5;10(16):7273-7286. doi: 10.7150/thno.44668. eCollection 2020.
Rattle-structured nanoparticles with movable cores, porous shells and hollow interiors have shown great effectiveness in drug delivery and cancer theranostics. Targeting autophagy and glucose have provided alternative strategies for cancer intervention therapy. Herein, rattle-structured polydopamine@mesoporous silica nanoparticles were prepared for photoacoustic (PA) imaging and augmented low-temperature photothermal therapy (PTT) via complementary autophagy inhibition and glucose metabolism. The multifunctional rattle-structured nanoparticles were designed with the nanocore of PDA and the nanoshell of hollow mesoporous silica (PDA@hm) via a four-step process. PDA@hm was then loaded with autophagy inhibitor chloroquine (CQ) and conjugated with glucose consumer glucose oxidase (GOx) (PDA@hm@CQ@GOx), forming a corona-like structure nanoparticle. The CQ and GOx were loaded into the cavity and decorated onto the surface of PDA@hm, respectively. The GOx-mediated tumor starvation strategy would directly suppress the expression of HSP70 and HSP90, resulting in an enhanced low-temperature PTT induced by PDA nanocore. In addition, autophagy inhibition by the released CQ made up for the loss of low-temperature PTT and starvation efficiencies by PTT- and starvation-activated autophagy, realizing augmented therapy efficacy. Furthermore, the PDA nanocore in the PDA@hm@CQ@GOx could be also used for PA imaging. Such a "drugs" loaded rattle-structured nanoparticle could be used for augmented low-temperature PTT through complementarily regulating glucose metabolism and inhibiting autophagy and photoacoustic imaging.
具有可动核、多孔壳和中空内部的响铃结构纳米粒子在药物输送和癌症治疗学中显示出了巨大的效果。靶向自噬和葡萄糖为癌症干预治疗提供了替代策略。在此，通过互补自噬抑制和葡萄糖代谢，制备了具有响铃结构的聚多巴胺@介孔硅纳米粒子用于光声（PA）成像和增强低温光热治疗（PTT）。多功能响铃结构纳米粒子通过四步过程设计，纳米核为 PDA，纳米壳为中空介孔硅（PDA@hm）。然后，PDA@hm 负载自噬抑制剂氯喹（CQ）并与葡萄糖消耗酶葡萄糖氧化酶（GOx）偶联（PDA@hm@CQ@GOx），形成类似冠状结构的纳米粒子。CQ 和 GOx 分别被装载到空腔中和 PDA@hm 的表面上。GOx 介导的肿瘤饥饿策略将直接抑制 HSP70 和 HSP90 的表达，导致由 PDA 纳米核引起的增强低温 PTT。此外，通过释放的 CQ 抑制自噬作用弥补了 PTT 和饥饿激活自噬引起的低温 PTT 和饥饿效率的损失，实现了增强的治疗效果。此外，PDA@hm@CQ@GOx 中的 PDA 纳米核也可用于 PA 成像。这种负载“药物”的响铃结构纳米粒子可用于增强低温 PTT，通过互补调节葡萄糖代谢和抑制自噬作用和光声成像。
