Qianqian Su

The effect of surface coating on energy migration-mediated upconversion.

Lanthanide-doped upconversion nanoparticles have been the focus of a growing body of investigation because of their promising applications ranging from data storage to biological imaging and drug delivery. Here we present the rational design, synthesis, and characterization of a new class of core-shell upconversion nanoparticles displaying unprecedented optical properties. Specifically, we show that the epitaxial growth of an optically inert NaYF(4) layer around a lanthanide-doped NaGdF(4)@NaGdF(4) core-shell nanoparticle effectively prevents surface quenching of excitation energy. At room temperature, the energy migrates over Gd sublattices and is adequately trapped by the activator ions embedded in host lattices. Importantly, the NaYF(4) shell-coating strategy gives access to tunable upconversion emissions from a variety of activators (Dy(3+), Sm(3+), Tb(3+), and Eu(3+)) doped at very low concentrations (down to 1 mol %). Our mechanistic investigations make possible, for the first time, the realization of efficient emissions from Tb(3+) and Eu(3+) activators that are doped homogeneously with Yb(3+)/Tm(3+) ions. The advances on these luminescent nanomaterials offer exciting opportunities for important biological and energy applications.

Ultrasensitive Near-Infrared Fluorescence-Enhanced Probe for in Vivo Nitroreductase Imaging

Nitroreductase (NTR) can be overexpressed in hypoxic tumors, thus the selective and efficient detection of NTR is of great importance. To date, although a few optical methods have been reported for the detection of NTR in solution, an effective optical probe for NTR monitoring in vivo is still lacking. Therefore, it is necessary to develop a near-infrared (NIR) fluorescent detection probe for NTR. In this study, five NIR cyanine dyes with fluorescence reporting structure decorated with different nitro aromatic groups, Cy7-1-5, have been designed and explored for possible rapid detection of NTR. Our experimental results presented that only a para-nitro benzoate group modified cyanine probe (Cy7-1) could serve as a rapid NIR fluorescence-enhanced probe for monitoring and bioimaging of NTR. The structure-function relationship has been revealed by theoretical study. The linker connecting the detecting and fluorescence reporting groups and the nitro group position is a key factor for the formation of hydrogen bonds and spatial structure match, inducing the NTR catalytic ability enhancement. The in vitro response and mechanism of the enzyme-catalyzed reduction of Cy7-1 have been investigated through kinetic optical studies and other methods. The results have indicated that an electro-withdrawing group induced electron-transfer process becomes blocked when Cy7-1 is catalytically reduced to Cy7-NH2 by NTR, which is manifested in enhanced fluorescence intensity during the detection process. Confocal fluorescence imaging of hypoxic A549 cells has confirmed the NTR detection ability of Cy7-1 at the cellular level. Importantly, Cy7-1 can detect tumor hypoxia in a murine hypoxic tumor model, showing a rapid and significant enhancement of its NIR fluorescence characteristics suitable for fluorescence bioimaging. This method may potentially be used for tumor hypoxia diagnosis.

Resonance Energy Transfer in Upconversion Nanoplatforms for Selective Biodetection

Resonance energy transfer (RET) describes the process that energy is transferred from an excited donor to an acceptor molecule, leading to a reduction in the fluorescence emission intensity of the donor and an increase in that of the acceptor. By this technique, measurements with the good sensitivity can be made about distance within 1 to 10 nm under physiological conditions. For this reason, the RET technique has been widely used in polymer science, biochemistry, and structural biology. Recently, a number of RET systems incorporated with nanoparticles, such as quantum dots, gold nanoparticles, and upconversion nanoparticles, have been developed. These nanocrystals retain their optical superiority and can act as either a donor or a quencher, thereby enhancing the performance of RET systems and providing more opportunities in excitation wavelength selection. Notably, lanthanide-doped upconversion nanophosphors (UCNPs) have attracted considerable attention due to their inherent advantages of large anti-Stoke shifts, long luminescence lifetimes, and absence of autofluorescence under low energy near-infrared (NIR) light excitation. These nanoparticles are promising for the biodetection of various types of analytes. Undoubtedly, the developments of those applications usually rely on resonance energy transfer, which could be regarded as a flexible technology to mediate energy transfer from upconversion phosphor to acceptor for the design of luminescent functional nanoplatforms. Currently, researchers have developed many RET-based upconversion nanosystems (RET-UCNP) that respond to specific changes in the biological environments. Specifically, small organic molecules, biological molecules, metal-organic complexes, or inorganic nanoparticles were carefully selected and bound to the surface of upconversion nanoparticles for the preparation of RET-UCNP nanosystems. Benefiting from the advantage and versatility offered by this technology, the research of RET-based upconversion nanomaterials should have significant implications for advanced biomedical applications. It should be noted that energy transfer in a UCNP based nanosystem is most often related to resonance energy transfer but that reabsorption (and maybe other energy transfer processes) may also play an important role and that more studies regarding the fundamental aspects for energy transfer with UCNPs is necessary. In this Account, we present an overview of recent advances in RET-based upconversion nanocomposites for biodetection with a particular focus on our own work. We have designed a series of upconversion nanoplatforms with remarkably high versatility for different applications. The experience gained from our strategic design and experimental investigations will allow for the construction of next-generation luminescent nanoplatform with marked improvements in their performance. The key aspects of this Account include fundamental principles, design and preparation strategies, biodetection in vitro and in vivo, future opportunities, and challenges of RET-UCNP nanosystems.

Ratiometric Monitoring of Intracellular Drug Release by an Upconversion Drug Delivery Nanosystem

Nanoscale drug delivery systems have been widely investigated due to their well-recognized advantages including controlled delivery of chemotherapeutic agents, enhanced therapeutic effectiveness, and reduced adverse effects compared to conventional chemotherapy with small molecules. However, further progress in the use of nanoscale delivery systems in clinical applications has been hampered by pharmacokinetic studies in biological samples which were associated with significant experimental challenges. Here, we report a rational ratiometric approach to monitor drug release kinetics by quantitatively investigating luminescence resonance energy transfer (LRET) from upconversion nanoparticles to the antitumor drug doxorubicin (DOX). Specifically, DOX molecules within the shell of mesoporous silica-coated upconversion nanoparticles selectively quenched the green emission of upconversion nanoparticles, while the intensity of red emission was essentially unaltered. Consequently, when DOX was gradually released, a steady recovery of green emission was observed. The ability to monitor the intensity ratio of green-to-red luminescence enabled a rational design for real-time investigation of drug delivery release kinetics. Importantly, the internal standard effect of red emission made this ratiometric approach suitable for complex biological microenvironments.

Near‐Infrared Upconversion Chemodosimeter for In Vivo Detection of Cu2+ in Wilson Disease

Near-infrared upconversion chemodosimetry is a promising detection method by virtue of the frequency upconversion technique, which shows very high sensitivity and selectivity for the detection of Cu(2+) ions in vitro and in vivo. This method offers a new opportunity for noninvasive diagnosis of Wilson disease associated with Cu(2+) detection in clinical medicine.

Ratiometric nanothermometer in vivo based on triplet sensitized upconversion

Temperature is an essential factor that counts for living systems where complicated vital activities are usually temperature dependent. In vivo temperature mapping based on non-contact optical approach will be beneficial for revealing the physiological phenomena behind with minimized influence to the organism. Herein, a highly thermal-sensitive upconversion system based on triplet–triplet annihilation (TTA) mechanism is pioneered to indicate body temperature variation sensitively over the physiological temperature range. The temperature-insensitive NaYF4: Nd nanophosphors with NIR emission was incorporated into the temperature-responsive TTA-upconversion system to serve as an internal calibration unit. Consequently, a ratiometric thermometer capable of accurately monitoring the temperature changes in vivo was developed with high thermal sensitivity (~7.1% K−1) and resolution (~0.1 K).Though luminescence imaging is a promising approach for contactless thermometry in vivo, the low thermal sensitivity of existing thermometers limits its potential. Here, the authors develop a high-sensitivity ratiometric nanothermometer based on triplet-sensitized upconversion.