Microenvironment-Driven Bioelimination of Magnetoplasmonic Nanoassemblies and Their Multimodal Imaging-Guided Tumor Photothermal Therapy Linlin Li,*,†,# Shiyan Fu,‡,# Chuanfang Chen,§,# Xuandong Wang,⊥ Changhui Fu,∥ Shu Wang,† Weibo Guo,† Xin Yu,† Xiaodi Zhang,† Zhirong Liu,† Jichuan Qiu,¶ and Hong Liu*,†,¶ †
Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, National Center for Nanoscience and Technology (NCNST), Beijing 100083, People’s Republic of China ‡ Mineral Resources Chemistry Key Laboratory of Sichuan Higher Education Institutions, College of Materials and Chemistry & Chemical Engineering, Chengdu University of Technology, Chengdu 610059, People’s Republic of China § Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China ⊥ Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361021, People’s Republic of China ∥ Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China ¶ State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, People’s Republic of China S Supporting Information *
ABSTRACT: Biocompatibility and bioelimination are basic requirements for systematically administered nanomaterials for biomedical purposes. Gold-based plasmonic nanomaterials have shown potential applications in photothermal cancer therapy. However, their inability to biodegrade has impeded practical biomedical application. In this study, a kind of bioeliminable magnetoplasmonic nanoassembly (MPNA), assembled from an Fe3O4 nanocluster and gold nanoshell, was elaborately designed for computed tomography, photoacoustic tomography, and magnetic resonance trimodal imaging-guided tumor photothermal therapy. A single dose of photothermal therapy under near-infrared light induced a complete tumor regression in mice. Importantly, MPNAs could respond to the local microenvironment with acidic pH and enzymes where they accumulated including tumors, liver, spleen, etc., collapse into small molecules and discrete nanoparticles, and finally be cleared from the body. With the bioelimination ability from the body, a high dose of 400 mg kg−1 MPNAs had good biocompatibility. The MPNAs for cancer theranostics pave a way toward biodegradable bio-nanomaterials for biomedical applications. KEYWORDS: plasmonic nanoparticles, bioelimination, biocompatibility, photothermal therapy, multimodal imaging
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Compared with organic nanomaterials, however, inorganic nanomaterials are generally more stable chemically and mechanically. These nanomaterials have been found to be able to exist in the body for a very long time over 2 years,12 which may bring many unpredictable risks. If the nanoparticles are unable to be bioeliminated, long-term accumulation in the body may induce irreversible damage to the body from the
norganic nanomaterials, ascribed to their unique physicochemical characteristics, have shown great potentials in biomedical applications and have been developed as drug delivery systems, imaging contrast agents, photothermal conversion agents,1−5 etc. Since the development of their biomedical applications, the in vivo toxicity of inorganic nanomaterials has received extensive attention. Many researchers have studied the effect of physicochemical properties of nanoparticles (NPs), such as particle size,6,7 shape,8,9 and surface chemistry,10,11 on the biodistribution and toxicity in vivo, and the tailoring of these parameters has been used to decrease the particle toxicity and change the biodistribution. © 2016 American Chemical Society
Received: May 16, 2016 Accepted: June 16, 2016 Published: June 16, 2016 7094
DOI: 10.1021/acsnano.6b03238 ACS Nano 2016, 10, 7094−7105
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ACS Nano severe oxidative stress,13 impairment of phagocytic activity of the mononuclear phagocyte system (MPS),14 etc. Clinic translation is possible only when the bioelimination of nanoparticles is realized to exclude the toxicity risk.15,16 After systematic administration, two possible pathways may be responsible for particle bioelimination from the body. One is that the nanoparticles would be directly excreted from the body, but it is only efficient for those smaller than the threshold of renal filtration. The other alternative way is that the nanoparticles could be degraded into harmless products and then excreted from the body. Gold-based plasmonic nanoparticles represent a typical group of inorganic nanomaterials for biological applications. With an efficient photothermal conversion effect at the nearinfrared (NIR) region, nanomaterials including gold nanoshells,17−19 gold nanorods,20,21 gold nanocages,22 and gold nanostars23 have been widely developed for photothermal cancer therapy and cancer theranostics. In order to tune the surface plasmon resonance (SPR) band from the visible region to the NIR region and ensure efficient accumulation of the nanoparticles in tumor tissues through the enhanced permeability and retention (EPR) effect, almost all of the plasmonic nanoparticles currently used for photothermal therapy have sizes larger than 50 nm. Therefore, they could not be directly excreted from the glomerulus filtration with a filtration threshold
