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WIREs Nanomed Nanobiotechnol
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Near‐infrared light‐responsive nanomaterials for cancer theranostics

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Abstract Early diagnosis and effective cancer therapy are required, to properly treat cancer, which causes more than 8.2 million deaths in a year worldwide. Among various cancer treatments, nanoparticle‐based cancer therapies and molecular imaging techniques have been widely exploited over the past decades to overcome current drawbacks of existing cancer treatments. In particular, gold nanoparticles (AuNPs), carbon nanotubes (CNTs), graphene oxide (GO), and upconversion nanocrystals (UNCs) have attracted tremendous attention from researchers due to their near‐infrared (NIR) light‐responsive behaviors. These nanomaterials are considered new multifunctional platforms for cancer theranostics. They would enable on‐demand control of drug release or molecular imaging in response to a remote trigger by NIR light exposure. This approach allows the patient or physician to adjust therapy precisely to a target site, thus greatly improving the efficacy of cancer treatments, while reducing undesirable side effects. In this review, we have summarized the advantages of NIR light‐responsive nanomaterials for in vivo cancer treatments, which includes NIR triggered photothermal therapy (PTT) and photodynamic therapy (PDT). Furthermore, recent developments, perspectives, and new challenges of NIR light‐responsive nanomaterials are discussed for cancer theranostic applications. WIREs Nanomed Nanobiotechnol 2015, 8:23–45. doi: 10.1002/wnan.1347 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Illustration of nanomaterials for cancer theranostics using NIR light.
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Suggested design for effective cancer treatment.
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I: (a) Schematic illustration of mesoporous silica‐coated UCNs coloaded with ZnPc and MC540 photosensitizers for PDT, (b) The emission spectrum of the UCN under 980‐nm NIR laser excitation and the absorption spectra of photosensitizers, (c) Cell viability after PDT treatment, (d) Photographs of a mouse having tumors (highlighted by dashed white circles) and (e) graph of tumor volumes in the four treatment groups. (Reprinted with permission from Ref . Copyright 2012 Nature Publishing Group) II: (a) schematic diagram of preparation of UCNP‐RGD and chemical structure of RGD, (b) Time‐dependent in vivo upconversion luminescence imaging of subcutaneous U87MG tumor and MCF‐7 tumor borne by athymic nude mice after intravenous injection of UCNP‐RGD over a 24 h period. (Reprinted with permission from Ref . Copyright 2009 American Chemical Society) III: (a) emission spectra of UCNPs, (b) photograph of UCNPs exposed to the 980 nm laser, (c) schematic illustration of UCNP‐based lymph node mapping, (d) i: a white light image of a mouse injected with UCNPs ii: a three‐color spectrally resolved in vivo UCL image showing different UCNP colors from the corresponding lymph nodes under the skin, iii: a white light image of the same mouse after dissection, iv: a UCL image of the dissected mouse. (e) UCNP injected mouse under white light and (f) in vivo cancer cell tracking and imaging after subcutaneous injection with three KB cell suspensions labeled by different colors of UCNPs. (Reprinted with permission from Ref . Copyright 2010 Springer) IV: (a) Schematic illustration of the NIR‐regulated drug delivery and the upconversion‐based photolysis of the prodrug, (b) TEM image of the YSUCNPs, (c) survival rate graph of mices intratumorally injected with YSUCNP‐ACCh (purple line), YSLnNP‐ACCh (green line), and 0.04 mL saline (blue line) and (d) photographs of corresponding tumor‐bearing mices injected with YSUCNP‐ACCh,YSLnNP‐ACCh and saline. (Reprinted with permission from Ref . Copyright 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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I: Graphene oxide for photothermal therapy. (a) Schematic illustration of PEG‐NGS‐Cy7, (b) AFM image of PEG‐NGS, (c) UV–vis‐NIR spectrum of a NGS‐PEG solution (inset: photo of NGS‐PEG solution) and (d) temperature curves of NGS‐PEG and water irradiated by 808 nm laser. (Reprinted with permission from Ref . Copyright 2010 American Chemical Society) II: (a) Schematic illustration of photothermal treatment using NGO‐HA conjugates for melanoma skin cancer, (b) viability of B16F1 melanoma and Detroit 551 cells under photothermal ablation therapy with NIR irradiation, (c) confocal image of NGO‐HA‐Hilyte647 conjugates in tumor model mice, (d) relative tumor volume with time, (e) Caspase‐3 activity in tumor tissues for a day for the analysis of heat induced apoptosis, and (f) Photographs of tumor model mice with NIR irradiation on the tumor growth inoculated with B16F1 cells on both dorsal flanks after topical administration of top: PBS, middle: NGO, and bottom: NGO‐HA. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society) III: Schematic illustration of the remote release of Dox from GO–polymer composite capsules using NIR light. (Reprinted with permission from Ref . Copyright 2013 Royal Society of Chemistry)
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I: Application of SWNT with amphiphilic polymer, PEG‐grafted poly(maleicanhydride‐alt‐1‐octadecene) (C 18 PMH‐PEG) for photothermal therapy. (a) A scheme of the animal experiment design. (b) Photothermal effects of the PEGylated SWNTs on 4T1 tumor‐bearing mice. (c) Cancer metastasis inhibition by the PEGylated SWNTs. (Reprinted with permission from Ref . Copyright 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) II: SWNT‐PEI and SWNT‐PVPk30 as a potential photosensitizer by determining ROS production and GSH reduction. (a) Treatment with significantly produced ROS in B16‐F10 cells analyzed by fluorescence microscope (up) and statistics evaluating fold change over control (down). (b) Evaluation GSH levels of SWNT‐PEI and SWNT‐PVPk30 with continuous illumination groups was decreased. (c) H&E staining of harvested cancer tissues from the mice. (Reprinted with permission from Ref . Copyright 2014 Royal Society of Chemistry) III: SWNT‐IRDye‐800 complex showing real‐time visualization by NIR‐ II fluorescence. (a) Schematic illustration of excitation by a 785‐nm laser; the SWNT‐IRDye‐800 complex emitted at the ∼800 nm NIR‐I from IRDye‐800 dye and the 1.1–1.4 µm NIR‐II from the SWNT. (b) Absorption spectrum of the SWNT–IRDye‐800 complex and emission spectrum of the dye and SWNTs. (c) Photograph of NIR‐II fluorescence, and (d) Schematic of imaging evaluation. (e) Image of real time arterial and venous vessels in time course. (Reprinted with permission from Ref . Copyright 2012 Rights Managed by Nature Publishing Group) IV: Immunostimulatory SWNT/CpG DNA complexes as a gene‐delivery cargo. (a–c) Inflammatory cytokines such as TNF‐α, IL‐6, and IL‐12p70 were elevated after being applied by the complex and (d) Cancer therapy by NIR laser in vivo. (Reprinted with permission from Ref . Copyright 2014 Elsevier B.V)
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I: PEG‐modified dendrimers consisting of AuNR core as photothermal agents. (a) Schematic illustration of the structure of PEG‐PAMAM dendron‐attached AuNR. (b) Photothermal effects on mice bearing colon carcinoma 26 cells under NIR irradiation (λ = 808 nm, 0.24 W/cm2). (c) Anti‐cancer performance of the PEGylated AuNRs. (Reprinted with permission from Ref . Copyright 2014 Royal Society of Chemistry) II: AuNR‐AlPcS4 complex as a photosensitizer producing singlet oxygen radicals inside cancer cells by process of disintegration. (a) Photothermal/photodynamic mechanism of the complex. (b) Photothermal activity and (c) Solid cancer treatment, measured in volume with the combination therapy. (Reprinted with permission from Ref . Copyright 2011 American Chemical Society) III: Cetuximab‐PEGylated AuNRs (CET‐PGNRs) as NIR absorber for imaging and photothermal therapy. (a) Total mechanism of the CET‐PGNR from synthesis to its cellular uptake and acting. (b) Time‐dependent real‐time NIR absorption images of cancer tissues, injected with CET‐PGNR (Reprinted with permission from Ref . Copyright 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) IV: Mesoporous silica‐encapsulated AuNRs ([email protected]2) for drug delivery and photothermal therapy with NIR radiation. (a) TEM images of AuNRs (b) doxorubicin (DOX) release profiles from the complexes depending on the pH, (c) thermal image of tumor‐bearing mice under 808 nm NIR laser, and (d) photographs of cancer size after excision; (1) control group, (2) laser group, (3) doxorubicin drug only group, (4) [email protected]2‐RGD with laser group, (5) DOX‐[email protected]2‐RGD with laser group. (Reprinted with permission from Ref . Copyright 2013 Elsevier Ltd)
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