期刊
BIOMATERIALS
卷 157, 期 -, 页码 107-124出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.12.003
关键词
Gold nanorod; Charge-reversal; Mitochondrial targeting; Reactive oxygen species; Photodynamic therapy; Photothermal therapy
资金
- National Key R&D Program of China [2016YFC1100300]
- National Natural Science Foundation of China [51673032, 51602034, 51603024]
- China Postdoctoral Science Foundation [2017M612919]
- Innovation Team in University of Chongqing Municipal Government [CXTDX201601002]
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 beta-cyclodextrin (beta-CD). Then, a peptide RLA ([RLARLAR](2)) 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. (C) 2017 Elsevier Ltd. All rights reserved.
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