Enhanced NIR Radiation-Triggered Hyperthermia by Mitochondrial Targeting

Jung, Hyo Sung; Han, Jiyou; Lee, Jae Hong; Lee, Ji Ha; Choi, Jong Min; Kweon, Hee Seok; Han, Ji Hye; Kim, Jong-Hoon; Byun, Kyung Min; Jung, Jong Hwa; Kang, Chulhun; Kim, Jong Seung

doi:10.1021/ja5122809

Cited by 170 publications

(105 citation statements)

References 34 publications

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“…174 A 740 nm NIR-triggered coumarin-based fluorescent iron oxide nanoparticle for mitochondrial targeting was shown to cause an enhanced hyperthermia effect and cytotoxicity against cancer cells. 175 …”

Section: Applications Of Light As a Therapeutic In Cancer Nanomedimentioning

confidence: 99%

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

et al. 2017

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Nanotechnology has begun to play a remarkable role in various fields of science and technology. In biomedical applications, nanoparticles have opened new horizons, especially for biosensing, targeted delivery of therapeutics, and so forth. Among drug delivery systems (DDSs), smart nanocarriers that respond to specific stimuli in their environment represent a growing field. Nanoplatforms that can be activated by an external application of light can be used for a wide variety of photoactivated therapies, especially light-triggered DDSs, relying on photoisomerization, photo-cross-linking/un-cross-linking, photoreduction, and so forth. In addition, light activation has potential in photodynamic therapy, photothermal therapy, radiotherapy, protected delivery of bioactive moieties, anticancer drug delivery systems, and theranostics (i.e., real-time monitoring and tracking combined with a therapeutic action to different diseases sites and organs). Combinations of these approaches can lead to enhanced and synergistic therapies, employing light as a trigger or for activation. Nonlinear light absorption mechanisms such as two-photon absorption and photon upconversion have been employed in the design of light-responsive DDSs. The integration of a light stimulus into dual/multiresponsive nanocarriers can provide spatiotemporal controlled delivery and release of therapeutic agents, targeted and controlled nanosystems, combined delivery of two or more agents, their on-demand release under specific conditions, and so forth. Overall, light-activated nanomedicines and DDSs are expected to provide more effective therapies against serious diseases such as cancers, inflammation, infections, and cardiovascular disease with reduced side effects and will open new doors toward the treatment of patients worldwide.

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Section: Applications Of Light As a Therapeutic In Cancer Nanomedimentioning

confidence: 99%

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

et al. 2017

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“…Recently, we reported a mitochondrial targeting hyperthermia-inducing agent using TPP-conjugated nanoparticles that induced mitochondrial dysfunction, resulting in apoptosis. 8 However, small organic molecules offer advantages relative to other nanomaterials, including in many instances improved safety as well as ease of preparation and modification. We therefore suggest that mitochondria-targeting PTT agents based on organic molecules might provide significant benefits.…”

Section: Introductionmentioning

confidence: 99%

A Mitochondria-Targeted Cryptocyanine-Based Photothermogenic Photosensitizer

et al. 2017

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Cryptocyanine-based probes exhibit highly efficient photothermal conversion and represent a new class of photothermal agents for use in photothermal therapy (PTT). With the thermal susceptibility of mitochondria in mind, we have prepared a mitochondria-targeted, NIR-absorbing cryptocyanine probe (Mito-CCy) and evaluated its photophysical properties, photothermal conversion efficiency, biological compatibility, cytotoxicity, and mitochondrial localization in HeLa cells. Upon subjecting 0.5 mL of a PBS buffer solution (10 mM, pH 7.4, containing 50% DMSO) of Mito-CCy (0.5 mM) to 730 nm laser irradiation at 2.3 W/cm2, the temperature of the solution increased by 13.5 °C within 5 min. In contrast, the corresponding cryptocyanine (CCy) lacking the triarylphosphonium group gave rise to only an ∼3.4 °C increase in solution temperature under otherwise identical conditions. Mito-CCy also exhibited high cytotoxicity in HeLa cells when subject to photoirradiation. This light-induced cytotoxicity is attributed to the endogenous production of reactive oxygen species (ROS) induced under conditions of local heating. ROS are known to interfere with the mitochondrial defense system and to trigger apoptosis. By targeting the mitochondria, the present sensitizer-based photothermogenic approach is rendered more effective. As such, the system reported here represents the vanguard of what might be a new generation of organelle-targeted photothermal therapeutics.

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“…Very recently, mitochondria-targeted PTT 34 and PDT 35, 36 have emerged as new strategies for improving therapeutic efficiency and safety, since mitochondria are vital energy-producing cellular organelles and highly susceptible to heat shock 37, generally resulting in apoptotic cell death through the generation of ROS 38. Thus we believe the combination of mitochondria-targeted PDT and PTT will bring preferable outcomes regarding to circumventing their respect limitations, reducing laser power density and materials dosage.…”

Section: Introductionmentioning

confidence: 99%

A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy

et al. 2017

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A new kind of green titania (G-TiO2-x) with obvious green color was facilely synthesized from black titania (B-TiO2-x) through subsequently strong ultrasonication. Comparatively, this stable G-TiO2-x shows much enhanced near infrared (NIR) absorption, especially around 920 nm, which can be ascribed to the obvious change of TiO2-x lattice order owing to the effect of ultrasonication. This feature enables G-TiO2-x to be stimulated with 980 nm laser in the combined photodynamic therapy (PDT) and photothermal therapy (PTT), which is greatly beneficial for improving tissue penetration depth. Furthermore, since mitochondria are preferred subcellular organelles for PDT/PTT, G-TiO2-x was further designed to conjugate with triphenylphosphonium (TPP) ligand for mitochondria-targeted PDT/PTT to obtain precise cancer treatment. Attributing to the high mitochondria-targeting efficiency and simultaneously synergistic PDT/PTT, high phototherapeutic efficacy and safety with a much lower laser power density (980 nm, 0.72 W cm-2) and low materials dosage were achieved both in vitro and in vivo. In addition, negligible toxicity was found, indicating high biocompatibility. This novel G-TiO2-x could provide new strategies for future precise minimal/non-invasive tumor treatment.

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Enhanced NIR Radiation-Triggered Hyperthermia by Mitochondrial Targeting

Cited by 170 publications

References 34 publications

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

A Mitochondria-Targeted Cryptocyanine-Based Photothermogenic Photosensitizer

A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy

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