Near‐Infrared Switchable Fullerene‐Based Synergy Therapy for Alzheimer's Disease

C₆₀ has a special dual function; it can act as both a powerful reactive oxygen species (ROS) producer under UV or visible light and an ROS scavenger in the dark. However, ROS has double‐edged effects in living systems. It is still a great challenge for biomedical application to switch and adjust the two opposite properties of C₆₀ in one system. Herein, UCNP@C₆₀‐pep (UCNP: upconversion nanoparticle, pep: Aβ‐target peptide KLVFF) is designed as a near‐infrared‐switchable nanoplatform for synergy therapy of Alzheimer's disease (AD). Under near‐infrared (NIR) light, the Aβ‐targeting hybrid nanoparticles produce ROS and result in Aβ photooxygenation, which can hinder Aβ aggregation and mitigate the attendant cytotoxicity. In the dark, UCNP@C₆₀‐pep shows protective effects against the increased oxidative stress. The ROS‐generating and ROS‐quenching abilities of UCNP@C₆₀‐pep are both beneficial for decreasing Aβ‐induced neurotoxicity and extending the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Moreover, UCNP@C60‐pep can also be used for upconversion luminescence (UCL) and magnetic resonance imaging (MRI), which has benefits for “image‐guided therapy.” This study may offer a new perspective for the biological applications of C₆₀.     

Nanotransducers for Near‐Infrared Photoregulation in Biomedicine

Photoregulation, which utilizes light to remotely control biological events, provides a precise way to decipher biology and innovate in medicine; however, its potential is limited by the shallow tissue penetration and/or phototoxicity of ultraviolet (UV)/visible light that are required to match the optical responses of endogenous photosensitive substances. Thereby, biologically friendly near‐infrared (NIR) light with improved tissue penetration is desired for photoregulation. Since there are a few endogenous biomolecules absorbing or emitting light in the NIR region, the development of molecular transducers is essential to convert NIR light into the cues for regulation of biological events. In this regard, optical nanomaterials able to convert NIR light into UV/visible light, heat, or free radicals are suitable for this task. Here, the recent developments of optical nanotransducers for NIR‐light‐mediated photoregulation in medicine are summarized. The emerging applications, including photoregulation of neural activity, gene expression, and visual systems, as well as photochemical tissue bonding, are highlighted, along with the design principles of nanotransducers. Moreover, the current challenges and perspectives in this field are discussed.     

Thermally Activated Upconversion Near‐Infrared Photoluminescence from Carbon Dots Synthesized via Microwave Assisted Exfoliation

Upconversion near‐infrared (NIR) fluorescent carbon dots (CDs) are important for imaging applications. Herein, thermally activated upconversion photoluminescence (UCPL) in the NIR region, with an emission peak at 784 nm, which appears under 808 nm continuous‐wave laser excitation, are realized in the NIR absorbing/emissive CDs (NIR‐CDs). The NIR‐CDs are synthesized by microwave‐assisted exfoliation of red emissive CDs in dimethylformamide, and feature single or few‐layered graphene‐like cores. This structure provides an enhanced contact area of the graphene‐like plates in the core with the electron‐acceptor carbonyl groups in dimethylformamide, which contributes to the main NIR absorption band peaked at 724 nm and a tail band in 800–850 nm. Temperature‐dependent photoluminescence spectra and transient absorption spectra confirm that the UCPL of NIR‐CDs is due to the thermally activated electron transitions in the excited state, rather than the multiphoton absorption process. Temperature dependent upconversion NIR luminescence imaging is demonstrated for NIR‐CDs embedded in a polyvinyl pyrrolidone film, and the NIR upconversion luminescence imaging in vivo using NIR‐CDs in a mouse model is accomplished.     

Quasi‐Continuous Wave Near‐Infrared Excitation of Upconversion Nanoparticles for Optogenetic Manipulation of C. elegans

Optogenetics is an emerging powerful tool to investigate workings of the nervous system. However, the use of low tissue penetrating visible light limits its therapeutic potential. Employing deep penetrating near‐infrared (NIR) light for optogenetics would be beneficial but it cannot be used directly. This issue can be tackled with upconversion nanoparticles (UCNs) acting as nanotransducers emitting at shorter wavelengths extending to the UV range upon NIR light excitation. Although attractive, implementation of such NIR‐optogenetics is hindered by the low UCN emission intensity that necessitates high NIR excitation intensities, resulting in overheating issues. A novel quasi‐continuous wave (quasi‐CW) excitation approach is developed that significantly enhances multiphoton emissions from UCNs, and for the first time NIR light‐triggered optogenetic manipulations are implemented in vitro and in C. elegans. The approach developed here enables the activation of channelrhodopsin‐2 with a significantly lower excitation power and UCN concentration along with negligible phototoxicity as seen with CW excitation, paving the way for therapeutic optogenetics.     

Upconversion Nanocarriers Encapsulated with Photoactivatable Ru Complexes for Near‐Infrared Light‐Regulated Enzyme Activity

Enzyme activity is important for metabolism, cell functions, and treating diseases. However, remote control of enzyme activity in deep tissue remains a challenge. This study demonstrates near‐infrared (NIR) light‐regulated enzyme activity in living cells based on upconverting nanoparticles (UCNPs) and a photoactivatable Ru complex. The Ru complex is a caged enzyme inhibitor that can be activated by blue light. To prepare a nanocarrier for NIR photoinhibition of enzyme activity, a UCNP and the caged enzyme inhibitors are encapsulated in a hollow mesoporous silica nanoparticle. In such a nanocarrier, the UCNP can harvest NIR light and convert it into blue light, which can activate the caged enzyme inhibitors. This photoactivation process is feasible in deep tissue because of the tissue penetration ability of NIR light. The nanocarrier is compatible to LNCaP, PC3, and SAOS‐2 cells, which show high enzyme expression. NIR irradiation induces release of the inhibitors and inhibition of enzyme activity in living cells. NIR light provides high spatiotemporal resolution to regulate enzyme activity in deep tissue.     

From UV to Near‐Infrared Light‐Responsive Metal–Organic Framework Composites: Plasmon and Upconversion Enhanced Photocatalysis

The exploitation of photocatalysts that harvest solar spectrum as broad as possible remains a high‐priority target yet grand challenge. In this work, for the first time, metal–organic framework (MOF) composites are rationally fabricated to achieve broadband spectral response from UV to near‐infrared (NIR) region. In the core–shell structured upconversion nanoparticles (UCNPs)‐Pt@MOF/Au composites, the MOF is responsive to UV and a bit visible light, the plasmonic Au nanoparticles (NPs) accept visible light, whereas the UCNPs absorb NIR light to emit UV and visible light that are harvested by the MOF and Au once again. Moreover, the MOF not only facilitates the generation of “bare and clean” Au NPs on its surface and realizes the spatial separation for the Au and Pt NPs, but also provides necessary access for catalytic substrates/products to Pt active sites. As a result, the optimized composite exhibits excellent photocatalytic hydrogen production activity (280 µmol g^?1 h^?1) under simulated solar light, and the involved mechanism of photocatalytic H₂ production under UV, visible, and NIR irradiation is elucidated. Reportedly, this is an extremely rare study on photocatalytic H₂ production by light harvesting in all UV, visible, and NIR regions.