Yuanwei Zhang

Amplifying the Red-Emission of Upconverting Nanoparticles for Biocompatible Clinically Used Prodrug-Induced Photodynamic Therapy

A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal β-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP–PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics.

Direct Aqueous-Phase Synthesis of Sub-10 nm "Luminous Pearls" with Enhanced in Vivo Renewable Near-Infrared Persistent Luminescence.

Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs), possessing unique NIR PL properties, have recently emerged as important materials for a wide variety of applications in chemistry and biology, for which they must endure high-temperature solid-state annealing reactions and subsequent complicated physical post-treatments. Herein, we report on a first direct aqueous-phase chemical synthesis route to NIR PLNPs and present their enhanced in vivo renewable NIR PL. Our method leads to monodisperse PLNPs as small as ca. 8 nm. Such sub-10 nm nanocrystals are readily dispersed and functionalized, and can form stable colloidal solutions in aqueous solution and cell culture medium for biological applications. Under biotissue-penetrable red-light excitation, we found that such nanocrystals possess superior renewable PL photoluminescence in vitro and in vivo compared to their larger counterparts currently made by existing methods. We believe that this solid-state-reaction-free chemical approach overcomes the current key roadblock in regard to PLNP development, and thus will pave the way to broad use of these advanced miniature “luminous pearls” in photonics and biophotonics.

Dye-Sensitized Core/Active Shell Upconversion Nanoparticles for Optogenetics and Bioimaging Applications.

Near-infrared (NIR) dye-sensitized upconversion nanoparticles (UCNPs) can broaden the absorption range and boost upconversion efficiency of UCNPs. Here, we achieved significantly enhanced upconversion luminescence in dye-sensitized core/active shell UCNPs via the doping of ytterbium ions (Yb(3+)) in the UCNP shell, which bridged the energy transfer from the dye to the UCNP core. As a result, we synergized the two most practical upconversion booster effectors (dye-sensitizing and core/shell enhancement) to amplify upconversion efficiency. We demonstrated two biomedical applications using these UCNPs. By using dye-sensitized core/active shell UCNP embedded poly(methyl methacrylate) polymer implantable systems, we successfully shifted the optogenetic neuron excitation window to a biocompatible and deep tissue penetrable 800 nm wavelength. Furthermore, UCNPs were water-solubilized with Pluronic F127 with high upconversion efficiency and can be imaged in a mouse model.

Highly Selective Fluorescence Turn-On Sensor for Fluoride Detection

Through click chemistry, triazole and triazolium groups have been explored to recognize anions through C-H···A(-) hydrogen-bonding complexion. Herein, we demonstrate evidence of fluoride-induced deprotonation of a C-H bond and its application in fluoride detection. The combination of fluorene and triazolium units produced a highly selective fluorescence turn-on prototype sensor for fluoride. The interactions between the C-H bond and F(-) were studied by fluorescence spectroscopy and (1)H NMR titrations. Test papers were prepared to detect fluoride in aqueous media at concentrations down to 1.9 ppm, important for estimating whether the fluoride concentration in drinking water is at a safe level.

Upconversion nanoparticles: a versatile solution to multiscale biological imaging.

Lanthanide-doped photon upconverting nanomaterials are emerging as a new class of imaging contrast agents, providing numerous unprecedented possibilities in the realm of biomedical imaging. Because of their ability to convert long-wavelength near-infrared excitation radiation into shorter-wavelength emissions, these nanomaterials are able to produce assets of low imaging background, large anti-Stokes shift, as well as high optical penetration depth of light for deep tissue optical imaging or light-activated drug release and therapy. The aim of this review is to line up some issues associated with conventional fluorescent probes, and to address the recent advances of upconverting nanoparticles (UCNPs) as a solution to multiscale biological imaging applications.

Ultralow-Power Near Infrared Lamp Light Operable Targeted Organic Nanoparticle Photodynamic Therapy

Tissue penetration depth is a major challenge in practical photodynamic therapy (PDT). A biocompatible and highly effective near infrared (NIR)-light-absorbing carbazole-substituted BODIPY (Car-BDP) molecule is reported as a class of imaging-guidable deep-tissue activatable photosensitizers for PDT. Car-BDP possesses an intense, broad NIR absorption band (600-800 nm) with a remarkably high singlet oxygen quantum yield (ΦΔ = 67%). After being encapsulated with biodegradable PLA-PEG-FA polymers, Car-BDP can form uniform and small organic nanoparticles that are water-soluble and tumor-targetable. Rather than using laser light, such nanoparticles offer an unprecedented deep-tissue, tumor targeting photodynamic therapeutic effect by using an exceptionally low-power-density and cost-effective lamp light (12 mW cm-2). In addition, these nanoparticles can be simultaneously traced in vivo due to their excellent NIR fluorescence. This study signals a major step forward in photodynamic therapy by developing a new class of NIR-absorbing biocompatible organic nanoparticles for effective targeting and treatment of deep-tissue tumors. This work also provides a potential new platform for precise tumor-targeting theranostics and novel opportunities for future affordable clinical cancer treatment.

In Vivo Repeatedly Charging Near-Infrared-Emitting Mesoporous SiO2/ZnGa2O4:Cr3+ Persistent Luminescence Nanocomposites

Near‐infrared (NIR) persistent phosphor ZnGa2O4:Cr3+ (ZGC) has unique deep‐tissue rechargeable afterglow properties. However, the current synthesis leads to agglomerated products with irregular morphologies and wide size distributions. Herein, we report on in vivo rechargeable mesoporous SiO2/ZnGa2O4:Cr3+ (mZGC) afterglow NIR‐emitting nanocomposites that are made by a simple, one‐step mesoporous template method. At less than 600 °C, pores in mesoporous silica nanoparticles (MSNs) act as nanoreactors to generate in situ ZnGa2O4:Cr3+ NIR‐persistent phosphors. The as‐synthesized mZGC preserves defined size, morphology, and mesoporous nanostructure of the MSNs. The persistent luminescence of the as‐synthesized mZGC is recharged in a simulated deep‐tissue environment (e.g., ≈8 mm pork slab) in vitro by using red light (620 nm). Moreover, mZGC can be repeatedly activated in vivo for persistent luminescence imaging in a live mouse model by using white LED as a light source. Our concept of utilizing mesoporous silica as nanoreactor to fabricate ZGC PL nanoparticles with controllable morphology and preserved porous nanostructure paves a new way to the development and the wide application of deep tissue rechargeable ZGC in photonics and biophotonics.

Bovine serum albumin nanoparticles with fluorogenic near-IR-emitting squaraine dyes.

Two squaraine (SQ) dyes, N-propanesulfonate-benzothiazolium squaraine (SQ-1) and N-propanesulfonate-benzoindolium squaraine (SQ-2), were synthesized with sulfonate groups to increase water solubility. Both dyes are almost nonfluorescent in aqueous solution with fluorescent quantum yields of 0.03, but exhibited fluorescence enhancement after noncovalently binding with bovine serum albumin (BSA). Upon addition of BSA, the fluorescence intensity increased by ca. a factor of 10, along with a 10-fold extension in the fluorescence lifetime. SQ-1 and SQ-2 interacted with BSA efficiently and appeared to show a preference for binding at site II, which involves combinational effects of electrostatic and hydrophobic interactions. The fluorogenic squaraine dyes were then used to label BSA, forming BSA-based nanoparticles (NPs) through noncovalent binding. The resulting BSA-SQ NPs exhibited enhanced near-IR fluorescence and reduced aggregation of the squaraine moiety. The BSA-SQ NPs were used for cell incubation and bioimaging studies. Confocal fluorescent images were obtained for HCT 116 cells incubated with the BSA-SQ NPs and LysoSensor Green, demonstrating the utility of the NP probes for intracellular imaging. This strategy ovecomes the generally low fluorescence emission of SQ dyes in water and aggregation-reduced fluorescence, providing a versatile strategy for sensing and imaging in biological environments.

Emerging ≈800 nm Excited Lanthanide‐Doped Upconversion Nanoparticles

Lanthanide-doped upconversion nanoparticles can tune near-infrared light to visible or even ultra-violet light in emissions. Due to their unique photophysical and photochemical properties, as well as their promising bioapplications, there has been a great deal of enthusiastic research performed to study the properties of lanthanide-doped upconversion nanoparticles in the past few years. Despite the considerable progress in this area, numerous challenges associated with the nanoparticles, such as a low upconversion efficiency, limited host materials, and a confined excitation wavelength, still remain, thus hindering further development with respect to their applications and in fundamental science. Recently, innovative strategies that utilize alternative sensitizers have been designed in order to engineer the excitation wavelengths of upconversion nanoparticles. Here, focusing on the excitation wavelength at ≈800 nm, recent advances in the design, property tuning, and applications of ≈800 nm excited upconversion nanoparticles are summarized. Benefiting from the unique features of ≈800 nm light, including deep tissue penetration depth and low photothermal effect, the ≈800 nm excited upconversion nanoparticles exhibit superior potential for biosensing, bioimaging, drug delivery, therapy, and three dimensional displays. The critical aspects of such emerging nanoparticles with regards to meeting the ever-changing needs of future development are also discussed.

Enhancing Photodynamic Therapy through Resonance Energy Transfer Constructed Near-Infrared Photosensitized Nanoparticles

Photodynamic therapy (PDT) is an important cancer treatment modality due to its minimally invasive nature. However, the efficiency of existing PDT drug molecules in the deep-tissue-penetrable near-infrared (NIR) region has been the major hurdle that has hindered further development and clinical usage of PDT. Thus, herein a strategy is presented to utilize a resonance energy transfer (RET) mechanism to construct a novel dyad photosensitizer which is able to dramatically boost NIR photon utility and enhance singlet oxygen generation. In this work, the energy donor moiety (distyryl-BODIPY) is connected to a photosensitizer (i.e., diiodo-distyryl-BODIPY) to form a dyad molecule (RET-BDP). The resulting RET-BDP shows significantly enhanced absorption and singlet oxygen efficiency relative to that of the acceptor moiety of the photosensitizer alone in the NIR range. After being encapsulated with biodegradable copolymer pluronic F-127-folic acid (F-127-FA), RET-BDP molecules can form uniform and small organic nanoparticles that are water soluble and tumor targetable. Used in conjunction with an exceptionally low-power NIR LED light irradiation (10 mW cm-2 ), these nanoparticles show superior tumor-targeted therapeutic PDT effects against cancer cells both in vitro and in vivo relative to unmodified photosensitizers. This study offers a new method to expand the options for designing NIR-absorbing photosensitizers for future clinical cancer treatments.