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WIREs Nanomed Nanobiotechnol
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Shedding light on nanomedicine

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Abstract Light is an electromagnetic radiation that can convert its energy into different forms (e.g., heat, chemical energy, and acoustic waves). This property has been exploited in phototherapy (e.g., photothermal therapy and photodynamic therapy (PDT)) and optical imaging (e.g., fluorescence imaging) for therapeutic and diagnostic purposes. Light‐controlled therapies can provide minimally‐ or noninvasive spatiotemporal control as well as deep tissue penetration. Nanotechnology provides numerous advantages, including selective targeting of tissues, prolongation of therapeutic effect, protection of active payloads, and improved therapeutic indices. This review explores the advances that nanotechnology can bring to light‐based therapies and diagnostics, and vice versa, including photo‐triggered systems, nanoparticles containing photoactive molecules, and nanoparticles that are themselves photoactive. Limitations of light‐based therapies such as photic injury and phototoxicity are discussed. WIREs Nanomed Nanobiotechnol 2012, 4:638–662. doi: 10.1002/wnan.1188 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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(a) Schematic of the electromagnetic spectrum of UV, visible, and IR light, and of the NIR window for in vivo imaging. (b) Energy diagram for conventional organic photoactives, molecular oxygen, and related photophysical and photochemical processes. hv, one‐photon absorption; 2hv, two‐photon absorption; S0, ground state; S1, singlet state; T1, triplet state. Fluorescence, photothermal therapy, and PDT are related to different transformation processes of the absorbed energy. For definition of type I and II reactions see Ref 3. (c) Schematic illustration of surface plasmon resonance of a metallic NP, which can absorb visible or NIR light by surface plasmonic resonance, and dissipate the absorbed light energy as heat (photothermal effect).

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Sample inorganic NPs used in phototherapy: gold NPs with various shapes and sizes, upconversion NPs, which can be excited by NIR light to emit UV or visible light, and mesoporous silica NPs, which contain porous nanostructures to encapsulate drugs.

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(a) Schematic of phototargeted polymeric NPs. Peptide targeting ligands (grey triangles) are inactivated by photocaging with o‐nitrobenzyl groups (pink circles). Illumination leads to cleavage of the photocaged group and reveals the active targeting ligand (green triangles), with subsequent binding of the targeted NPs to the irradiated tissue sites. (b) Photoswitchable NPs (150 nm, orange spheres) can shrink to 40 nm (purple spheres) upon light illumination. The smaller NPs will have enhanced tissue penetration. Release of drugs (bright yellow spheres) loaded in the NPs is simultaneously triggered by light.

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Three commonly used photoswitching reactions in light‐triggered drug delivery system.

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General photocaging strategy and commonly used photocaging protection groups.

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(a) Conventional optical imaging methods suffer from scattering in biological tissues. (b) Propagation of ultrasound in tissue. Using laser pulses to generate elastic pressure waves (ultrasound) allows high‐resolution optical information to be obtained since ultrasonic scattering is two to three orders of magnitude less than optical scattering.

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Advantages of using NPs in phototherapy. (a) Administered free photoactives have low accumulation in tumor and distribute to the whole body. Photoactives in healthy tissue may be activated by ambient visible light and cause off‐target toxicity. (b) NPs can enhance accumulation of photoactives at disease sites (e.g., tumors) by EPR effect to improve phototherapy efficacy.

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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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