Integration of IR‐808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR‐excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR‐808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)‐functionalized silica layer is developed for PDT agent. The two booster effectors (dye‐sensitization and core–shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS₂ nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS₂ nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.     

Minimizing the Heat Effect of Photodynamic Therapy Based on Inorganic Nanocomposites Mediated by 808 nm Near‐Infrared Light

Photodynamic therapy (PDT) based on photosensitizers (PSs) constructed with nanomaterials has become popular in cancer treatment, especially oral carcinoma cell. This therapy is characterized by improved PS accumulation in tumor regions and generation of reactive oxygen species (ROS) for PDT under specific excitation. In the selection of near‐infrared (NIR) window, 808 nm NIR light because it can avoid the absorption of water is particularly suitable for the application in PDT. Hence, multiband emissions under a single 808 nm near‐infrared excitation of Nd³⁺‐sensitized upconversion nanoparticles (808 nm UCNPs) have been applied for the PDT effect. 808 nm UCNPs serve as light converter to emit UV light to excite inorganic PS, graphitic carbon nitride quantum dots (CNQDs), thereby generating ROS. In this study, a nanocomposite consisting UCNPs conjugated with poly‐l ‐lysine (PLL) to improve binding with CNQDs is fabricated. According to the research results, NIR‐triggered nanocomposites of 808 nm UCNP‐PLL@CNs have been verified by significant improvement in ROS generation. Consequently, 808 nm UCNP‐PLL@CNs exhibit high capability for ROS production and efficient PDT in vitro and in vivo. Moreover, the mechanism of PDT treatment by 808 nm UCNP‐PLL@CNs is evaluated using the cell apoptosis pathway.     

Engineering of Lanthanide‐Doped Upconversion Nanoparticles for Optical Encoding

Lanthanide‐doped upconversion nanoparticles (UCNPs) are an emerging class of luminescent materials that emit UV or visible light under near infra‐red (NIR) excitations, thereby possessing a large anti‐Stokes shift property. Due to their sharp excitation and emission bands, excellent photo‐ and chemical stability, low autofluorescence, and high tissue penetration depth of the NIR light used for excitation, UCNPs have surpassed conventional fluorophores in many bioapplications. A better understanding of the mechanism of upconversion, as well as the development of better approaches to preparing UCNPs, have provided more opportunities to explore their use for optical encoding, which has the potential for applications in multiplex detection and imaging. With the current ability to precisely control the microstructure and properties of UCNPs to produce particles of tunable emission, excitation, luminescence lifetime, and size, various strategies for optical encoding based on UCNPs can now be developed. These optical properties of UCNPs (such as emission and excitation wavelengths, ratiometric intensity, luminescence lifetime, and multicolor patterns), and the strategies employed to engineer these properties for optical encoding of UCNPs through homogeneous ion doping, heterogeneous structure fabrication and microbead encapsulation are reviewed. The challenges and potential solutions faced by UCNP optical encoding are also discussed.     

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.     

DNA‐Assembled Core‐Satellite Upconverting‐Metal–Organic Framework Nanoparticle Superstructures for Efficient Photodynamic Therapy

DNA‐mediated assembly of core–satellite structures composed of Zr(IV)‐based porphyrinic metal‐organic framework (MOF) and NaYF₄,Yb,Er upconverting nanoparticles (UCNPs) for photodynamic therapy (PDT) is reported. MOF NPs generate singlet oxygen (¹O₂) upon photoirradiation with visible light without the need for additional small molecule, diffusional photosensitizers such as porphyrins. Using DNA as a templating agent, well‐defined MOF–UCNP clusters are produced where UCNPs are spatially organized around a centrally located MOF NP. Under NIR irradiation, visible light emitted from the UCNPs is absorbed by the core MOF NP to produce ¹O₂ at significantly greater amounts than what can be produced from simply mixing UCNPs and MOF NPs. The MOF–UCNP core–satellite superstructures also induce strong cell cytotoxicity against cancer cells, which are further enhanced by attaching epidermal growth factor receptor targeting affibodies to the PDT clusters, highlighting their promise as theranostic photodynamic agents.     

A Novel Theranostic Nanoprobe for In Vivo Singlet Oxygen Detection and Real‐Time Dose–Effect Relationship Monitoring in Photodynamic Therapy

Singlet oxygen, as the main member of reactive oxygen species, plays a significant role in cancer photodynamic therapy. However, the in vivo real‐time detection of singlet oxygen remains challenging. In this work, a Förster resonance energy transfer (FRET)‐based upconversion nanoplatform for monitoring the singlet oxygen in living systems is developed, with the ability to evaluate the in vivo dose–effect relationship between singlet oxygen and photodynamic therapy (PDT) efficacy. In details, this nanoplatform is composed of core–shell upconversion nanoparticles (UCNPs), photosensitizer MC540, NIR dye IR‐820, and poly(acryl amine) PAA‐octylamine, where the UCNPs serve as an energy donor while IR‐820 serves as an energy acceptor. The nanoparticles are found to sensitively reflect the singlet oxygen levels generated in the tumor tissues during PDT, by luminescence intensity changes of UNCPs at 800 nm emission. Furthermore, it could also enable tumor treatment with satisfactory biocompatibility. To the best knowledge, this is the first report of a theranostic nanoplatform with the ability to formulate the in vivo dose–effect relationship between singlet oxygen and PDT efficacy and to achieve tumor treatment at the same time. This work might also provide an executable strategy to evaluate photodynamic therapeutic efficacy based on singlet oxygen pathway.     

Near-infrared light activated persistent luminescence nanoparticles via upconversion

Persistent luminescence nanoparticles (PLNPs) and upconversion nanoparticles (UCNPs) are two special optical imaging nanoprobes.In this study,efficient upconverted persistent luminescence (UCPL) is realized by combining their unique features into polymethyl methacrylate,forming a film composed of both PLNPs and UCNPs.The red persistent luminescence (～640 nm) of the PLNPs (CaS∶Eu,Tm,Ce) can be activated by upconverted green emission of UCNPs (β-NaYF4∶Yb,Er@NaYF4) excited by near-infrared light (NIR).Using this strategy,both the unique optical properties of PLNPs and UCNPs can be optimally synergized,thus generating efficient upconversion,photoluminescence,and UCPL simultaneously.The UCPL system has potential applications in in vivo bioimaging by simply monitoring the biocompatible low power density of NIR-light-excited persistent luminescence.Due to its simplicity,we anticipate that this method for the preparation of UCPL composite can be easily adjusted using other available upconversion and persistent phosphor pairs for a number of biophotonic and photonic applications.     

稀土掺杂上转换发光纳米材料在有机光伏器件中的应用进展

稀土掺杂上转换发光纳米材料(UCNPs)是一种在近红外光激发下发出可见光的纳米材料,将UCNPs掺入有机光伏电池中,可以扩大有机光伏电池对太阳光谱的响应范围,提高有机光伏电池的光电转换效率。综述了UCNPs在染料敏化太阳能电池、聚合物太阳能电池中的应用进展,展望了该材料未来的研究方向。     

On The Latest Three‐Stage Development of Nanomedicines based on Upconversion Nanoparticles

Following the “detect‐to‐treat” strategy, by biological engineering, the emerging upconversion nanoparticles (UCNPs) have become one of the most promising inorganic nanomedicines, and their biomedical applications have gradually shifted from multimodal tumor imaging to highly efficient cancer therapy. The past few years have witnessed a three‐stage development of UCNP‐based nanomedicines. On one hand, UCNPs can optimize each clinical treatment tool (chemotherapy, photodynamic therapy (PDT), radiotherapy (RT)) by controlled drug delivery/release, near‐infrared (NIR)‐excited deep PDT, and radiosensitization, respectively, all of which contribute greatly to the optimized treatment efficacy along with minimized side effects. On the other hand, several individual treatments can be “smartly” integrated into a single UCNP‐based nanotheranostic system for multimodal synergetic therapy, which can further improve the overall therapeutic effectiveness. Especially, UCNPs provide more‐effective strategies for overcoming tumor hypoxia, thus leading to an ideal treatment efficacy for complete eradication of solid tumors. Finally, the critical issues regarding the future development of UCNPs are discussed to promote the clinic‐translational applications of UCNP‐based nanomedicines, as well as realization of our “one drug fits all” dream.     

Recent Progress in Near Infrared Light Triggered Photodynamic Therapy

Nowadays, photodynamic therapy (PDT) is under the research spotlight as an appealing modality for various malignant tumors. Compared with conventional PDT treatment activated by ultraviolet or visible light, near infrared (NIR) light‐triggered PDT possessing deeper penetration to lesion area and lower photodamage to normal tissue holds great potential for in vivo deep‐seated tumor. In this review, recent research progress related to the exploration of NIR light responsive PDT nanosystems is summarized. To address current obstacles of PDT treatment and facilitate the effective utilization, several innovative strategies are developed and introduced into PDT nanosystems, including the conjugation with targeted moieties, O₂ self‐sufficient PDT, dual photosensitizers (PSs)‐loaded PDT nanoplatform, and PDT‐involved synergistic therapy. Finally, the potential challenges as well as the prospective for further development are also discussed.     

Recent Advances in Upconversion Nanoparticles‐Based Multifunctional Nanocomposites for Combined Cancer Therapy

Lanthanide‐doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous‐wave near‐infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue‐penetration ability and high signal‐to‐noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging‐guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co‐delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti‐cancer effects, reduces individual drug‐related toxicity and suppresses multi‐drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs‐based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs‐based composites. The future prospects and challenges in this emerging field will be also discussed.     

Upconversion Nanoparticles–Based Multiplex Protein Activation to Neuron Ablation for Locomotion Regulation

The optogenetic neuron ablation approach enables noninvasive remote decoding of specific neuron function within a complex living organism in high spatiotemporal resolution. However, it suffers from shallow tissue penetration of visible light with low ablation efficiency. This study reports a upconversion nanoparticle (UCNP)–based multiplex proteins activation tool to ablate deep‐tissue neurons for locomotion modulation. By optimizing the dopant contents and nanoarchitecure, over 300‐fold enhancement of blue (450–470 nm) and red (590–610 nm) emissions from UCNPs is achieved upon 808 nm irradiation. Such emissions simultaneously activate mini singlet oxygen generator and Chrimson, leading to boosted near infrared (NIR) light–induced neuronal ablation efficiency due to the synergism between singlet oxygen generation and intracellular Ca²⁺ elevation. The loss of neurons severely inhibits reverse locomotion, revealing the instructive role of neurons in controlling motor activity. The deep penetrance NIR light makes the current system feasible for in vivo deep‐tissue neuron elimination. The results not only provide a rapidly adoptable platform to efficient photoablate single‐ and multiple‐cells, but also define the neural circuits underlying behavior, with potential for development of remote therapy in diseases.     

Red‐Emitting Upconverting Nanoparticles for Photodynamic Therapy in Cancer Cells Under Near‐Infrared Excitation

Upconverting nanoparticles (UCNPs) have attracted considerable attention as potential photosensitizer carriers for photodynamic therapy (PDT) in deep tissues. In this work, a new and efficient NIR photosensitizing nanoplatform for PDT based on red‐emitting UCNPs is designed. The red emission band matches well with the efficient absorption bands of the widely used commercially available photosensitizers (Ps), benefiting the fluorescence resonance energy transfer (FRET) from UCNPs to the attached photosensitizers and thus efficiently activating them to generate cytotoxic singlet oxygen. Three commonly used photosensitizers, including chlorine e6 (Ce6), zinc phthalocyanine (ZnPc) and methylene blue (MB), are loaded onto the alpha‐cyclodextrin‐modified UCNPs to form Ps@UCNPs complexes that efficiently produce singlet oxygen to kill cancer cells under 980 nm near‐infrared excitation. Moreover, two different kinds of drugs are co‐loaded onto these nanoparticles: chemotherapy drug doxorubicin and PDT agent Ce6. The combinational therapy based on doxorubicin (DOX)‐induced chemotherapy and Ce6‐triggered PDT exhibits higher therapeutic efficacy relative to the individual means for cancer therapy in vitro.     

Remote Light‐Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives

Engineering of smart photoactivated nanomaterials for targeted drug delivery systems (DDS) has recently attracted considerable research interest as light enables precise and accurate controlled release of drug molecules in specific diseased cells and/or tissues in a highly spatial and temporal manner. In general, the development of appropriate light‐triggered DDS relies on processes of photolysis, photoisomerization, photo‐cross‐linking/un‐cross‐linking, and photoreduction, which are normally sensitive to ultraviolet (UV) or visible (Vis) light irradiation. Considering the issues of poor tissue penetration and high phototoxicity of these high‐energy photons of UV/Vis light, recently nanocarriers have been developed based on light‐response to low‐energy photon irradiation, in particular for the light wavelengths located in the near infrared (NIR) range. NIR light‐triggered drug release systems are normally achieved by using two‐photon absorption and photon upconversion processes. Herein, recent advances of light‐responsive nanoplatforms for controlled drug release are reviewed, covering the mechanism of light responsive small molecules and polymers, UV and Vis light responsive nanocarriers, and NIR light responsive nanocarriers. NIR‐light triggered drug delivery by two‐photon excitation and upconversion luminescence strategies is also included. In addition, the challenges and future perspectives for the development of light triggered DDS are highlighted.     

Preparation, characterization and cytotoxicity of carbon nanotube-chitosan-phycocyanin complex

Photodynamic therapy (PDT) or photothermal therapy (PTT) using nanomaterials has shown great prospect for cancer treatment. Phycocyanin (PC) is a photoharvesting pigment and is also an attractive candidate for PDT. The multiwalled carbon nanotube (MWNT) is a potent candidate for PTT due to its extraordinary photo-to-thermal energy conversion efficiency upon excitation with near-infrared (NIR) light. To date, although MWNT-CS complexes have been well studied, no report about the reconjugation of MWNT-CS with phycocyanin is available in the literature. Here, by using water-soluble chitosan (CS), we prepared and characterized a novel biomaterial, MWNT-CS-PC, with the potential for PDT and PTT. The cytotoxicity experiments found that MWNT-CS-PC exhibited cell growth inhibition activity. Moreover, with irradiation of NIR light (808?nm) or visible light (532?nm), the photoinduced cytotoxicity was indeed enhanced. These results suggest that MWNT-CS-PC may potentially serve as a future photodynamic and photothermal therapy for cancer.     

Controllable synthesis of NaYF(4) : Yb,Er upconversion nanophosphors and their application to in vivo imaging of Caenorhabditis elegans

β-NaYF(4) : Yb,Er upconversion nanoparticles (UCNPs) can emit bright green fluorescence under near-infrared (NIR) light excitation which is safe to the body and can penetrate deeply into tissues. The application of UCNPs in biolabeling and imaging has received great attention recently. In this work, β-NaYF(4) : Yb,Er UCNPs with an average size of 35 nm, uniformly spherical shape, and surface modified with amino groups were synthesized by a one-step green solvothermal approach through the use of room-temperature ionic liquids as the reactant, co-solvent and template. The as-prepared UCNPs were introduced into Caenorhabditis elegans (C. elegans) to achieve successful in vivo imaging. We found that longer incubation time, higher UCNP concentration and smaller UCNP size can make the in vivo fluorescence of C. elegans much brighter and more continuous along their body. The worms have no apparent selectivity on ingestion of the UCNPs capped with different capping ligands while having similar size and shape. The next generation of worms did not show fluorescence under excitation. In addition, low toxicity of the nanoparticles was demonstrated by investigating the survival rates of the worms in the presence of the UCNPs. Our work demonstrates the potential application of the UCNPs in studying the biological behavior of organisms, and lays the foundation for further development of the UCNPs in the detection and diagnosis of diseases.     

Study on NIR optical rewritable film based on dithienylethene and upconversion nanocrystals

Tm3+ and Yb3+ codoped NaYF4 upconversion (UC) nanoparticles (NPs) with intense ultraviolet (UV) fluorescence were synthesized using a solvothermal approach. NIR optical rewritable film incorporated with the UCNPs and dithienylethene (DTE) were performed for optical storage based on the photochromic reaction of DTE induced by the intense UV from themultiphoton UC fluorescence of NaYF4NPs. The photochromic DTE did not exhibit obvious fatigue after repetitious write/erase cycles using NIR/green irradiation.     

Hybrid Nanoparticle Pyramids for Intracellular Dual MicroRNAs Biosensing and Bioimaging

This study strategically fabricates multifunctional nanopyramids to allow the ultrasensitive quantification of dual microRNAs (miR‐203^b and miR‐21) in living cells and their responsive bioimaging in vivo. The nanopyramids, composed of Au‐Cu₉S₅ nanoparticles (NPs), upconversion NPs (UCNPs), and Ag₂S NPs, emit two luminescent signals simultaneously with excitation at 808 nm, arising from the UCNPs at 541 nm in the visible region and from the Ag₂S NPs at 1227 nm in the second window of near‐infrared (NIR‐II) region. The upconversion luminescence has a linear relationship with miR‐203^b from 0.13 to 54.54 fmol per 10 µg_RNA and a limit of detection (LOD) of 0.09 fmol per 10 µg_RNA, whereas the Ag₂S NP luminescence has a linear relationship with miR‐21 from 0.37 to 43.56 fmol per 10 µg_RNA, with a LOD of 0.23 fmol per 10 µg_RNA. Significantly, this study demonstrates that the nanopyramids can be successfully used for miRs‐responsive bioimaging in a tumor‐bearing animal model. Furthermore, taking advantage of the photothermal capabilities of pyramids, the tumors can also be eliminated completely. These nanopyramids not only overcome the obstacles in the simultaneous detection of multiple miRs at the cellular level but also provide a cancer theranostic platform in vivo.     

Glutathione Mediated Size‐Tunable UCNPs‐Pt(IV)‐ZnFe2O4 Nanocomposite for Multiple Bioimaging Guided Synergetic Therapy

Here a multifunctional nanoplatform (upconversion nanoparticles (UCNPs)‐platinum(IV) (Pt(IV))?ZnFe₂O₄, denoted as UCPZ) is designed for collaborative cancer treatment, including photodynamic therapy (PDT), chemotherapy, and Fenton reaction. In the system, the UCNPs triggered by near‐infrared light can convert low energy photons to high energy ones, which act as the UV–vis source to simultaneously mediate the PDT effect and Fenton's reaction of ZnFe₂O₄ nanoparticles. Meanwhile, the Pt(IV) prodrugs can be reduced to high virulent Pt(II) by glutathione in the cancer cells, which can bond to DNA and inhibit the copy of DNA. The synergistic therapeutic effect is verified in vitro and in vivo results. The cleavage of Pt(IV) from UCNPs during the reduction process can shift the larger UCPZ nanoparticles (NPs) to the smaller ones, which promotes the enhanced permeability and retention (EPR) and deep tumor penetration. In addition, due to the inherent upconversion luminescence (UCL) and the doped Yb³⁺ and Fe³⁺ in UCPZ, this system can serve as a multimodality bioimaging contrast agent, covering UCL, X‐ray computed tomography, magnetic resonance imaging, and photoacoustic. A smart all‐in‐one imaging‐guided diagnosis and treatment system is realized, which should have a potential value in the treatment of tumor.     

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.