Large anti-Stokes Shift Research Articles

Upconversion nanophosphors for use in bioimaging, therapy, drug delivery and bioassays

Upconversion nanoparticles (UCNPs) represent a new class of fluorophores. Both the excitation and (anti-Stokes) emission wavelengths are in the long wave part of the spectrum so that their luminescence can deeply penetrate tissues and cause low photodamage in biological samples. Their large anti-Stokes shifts, sharp emission bands, zero auto-fluorescence from biological samples and high photostability renders them an ideal kind of fluorescent labels for a variety of analytical formats, for bioimaging in cancer therapy. This review covers the basic mechanisms of up-conversion luminescence, the methods for the synthesis and surface modification of biocompatible UCNPs, and aspects of the in vivo delivery of UCNPs. More specifically, we discuss (a) recent progress regarding UCNPs for multimodal targeted tumor imaging, (b) UCNP-based methods of biological detection and sensing, (c) the use of UCNPs in drug delivery, (d) applications in photodynamic therapy, photothermal therapy and radiotherapy. Finally, we are addressing challenges and opportunities of this quickly emerging field. Contains 362 references.

ChemInform Abstract: Lanthanide‐Doped Luminescent Nanoprobes: Controlled Synthesis, Optical Spectroscopy, and Bioapplications

AbstractReview: 364 refs.

A Cyanine-Modified Nanosystem forin VivoUpconversion Luminescence Bioimaging of Methylmercury

Methylmercury (MeHg(+)) is a strong liposoluble ion, which can be accumulated in the organs of animals and can cause prenatal nervous system and visceral damage. Therefore, the efficient and sensitive monitoring of MeHg(+) in organisms is of great importance. Upconversion luminescence (UCL) detection based on rare-earth upconversion nanophosphors (UCNPs) as probes has been proved to exhibit a large anti-Stokes shift, no autofluorescence from biological samples, a remarkably deep penetration depth, and no photobleaching. In this study, a hydrophobic heptamethine cyanine dye (hCy7) modified by two long alkyl moieties and amphiphilic polymer (P-PEG)-modified nanophosphors (hCy7-UCNPs) was fabricated as a highly sensitive water-soluble probe for UCL monitoring and bioimaging of MeHg(+). Further application of hCy7-UCNPs for sensing MeHg(+) was confirmed by an optical titration experiment and upconversion luminescence live cell imaging. Using the ratiometric upconversion luminescence as a detection signal, which provides a built-in correction for environmental effects, the detection limit of MeHg(+) for this nanosystem was as low as 0.18 ppb. Importantly, the hCy7-UCNPs nanosystem was shown to be capable of monitoring MeHg(+)ex vivo and in vivo by upconversion luminescence bioimaging.

Approaches to the Multicolor Tuning of Lanthanide-Ion Doped Upconversion Nanoparticles

In recent years, lanthanide-ion doped nanocrystals have attracted considerable attention for its promising applications in multiplexed biological labeling. These materials can convert near-infrared (NIR) light into visible and offer low autofluorescence, high resistance to photobleaching, high penetration depth and large anti-Stokes shifts. With the development of these techniques, the ability to manipulate multicolor output has become more important for its biological and photovoltaic applications. This review mainly focuses on the recent development of various approaches for the multicolor tuning of lanthanide-ion doped upconversion nanoparticles.

Lanthanide-doped luminescent nanoprobes: controlled synthesis, optical spectroscopy, and bioapplications

Lanthanide-doped inorganic nanoparticles possess superior physicochemical features such as long-lived luminescence, large antenna-generated Stokes or anti-Stokes shifts, narrow emission bands, high resistance to photobleaching and low toxicity, and thus are regarded as a new generation of luminescent bioprobes as compared to conventional molecular probes like organic dyes and lanthanide chelates. These functional nanoparticles, although most of their bulk counterparts were well studied previously, have attracted renewed interest for their biomedical applications in areas as diverse as biodetection, bioimaging, and disease diagnosis and therapeutics. In this review, we provide a comprehensive survey of the latest advances made in developing lanthanide-doped inorganic nanoparticles as potential luminescent bioprobes, which covers areas from their fundamental chemical and physical features to bioapplications including controlled synthesis methodology, surface modification chemistry, optical spectroscopy, and their promising applications in diverse fields, with an emphasis on heterogeneous and homogeneous in vitro biodetection of tumor markers and multimodal bioimaging of various tumor tissues. Some future prospects and challenges in this rapidly growing field are also summarized.

Triple-functional core–shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro

Upconversion luminescent nanoparticles (UCNPs) have been widely used in many biochemical fields, due to their characteristic large anti-Stokes shifts, narrow emission bands, deep tissue penetration and minimal background interference. UCNPs-derived multifunctional materials that integrate the merits of UCNPs and other functional entities have also attracted extensive attention. Here in this paper we present a core-shell structured nanomaterial, namely, NaGdF(4):Yb,Er@CaF(2)@SiO(2)-PS, which is multifunctional in the fields of photodynamic therapy (PDT), magnetic resonance imaging (MRI) and fluorescence/luminescence imaging. The NaGdF(4):Yb,Er@CaF(2) nanophosphors (10 nm in diameter) were prepared via sequential thermolysis, and mesoporous silica was coated as shell layer, in which photosensitizer (PS, hematoporphyrin and silicon phthalocyanine dihydroxide) was covalently grafted. The silica shell improved the dispersibility of hydrophobic PS molecules in aqueous environments, and the covalent linkage stably anchored the PS molecules in the silica shell. Under excitation at 980 nm, the as-fabricated nanomaterial gave luminescence bands at 550 nm and 660 nm. One luminescent peak could be used for fluorescence imaging and the other was suitable for the absorption of PS to generate singlet oxygen for killing cancer cells. The PDT performance was investigated using a singlet oxygen indicator, and was investigated in vitro in HeLa cells using a fluorescent probe. Meanwhile, the nanomaterial displayed low dark cytotoxicity and near-infrared (NIR) image in HeLa cells. Further, benefiting from the paramagnetic Gd(3+) ions in the core, the nanomaterial could be used as a contrast agent for magnetic resonance imaging (MRI). Compared with the clinical commercial contrast agent Gd-DTPA, the as-fabricated nanomaterial showed a comparable longitudinal relaxivities value (r(1)) and similar imaging effect.

Luminescence resonance energy transfer based on β-NaYF4:Yb,Er nanoparticles and TRITC dye

β-NaYF4:Yb,Er nanoparticles (NPs) are one of the most efficient upconversion materials, which can convert near-infrared light to higher-energy light through multiple photon absorptions or energy transfer. In addition, they may be attractive alternative donors for luminescence resonance energy transfer (LRET) studies, because of their sharp absorption and emission profiles, high quantum yields, large anti-stokes shifts, long lifetime, low toxicity, and superior photo-stability. In principle, many problems of fluorescence resonance energy transfer (FRET), such as excitation of acceptors, emission overlaps between donors and acceptors, high background noise, potential toxicity, and instability, can be overcome using β-NaYF4:Yb,Er NPs as energy donors. Because the organic coating induced separation can significantly reduce the energy transfer efficiency and aqueous FRET system is difficult to be applied in devices, we demonstrate a novel NP-dye LRET system in solid state. The emission of the β-NaYF4:Yb,Er NPs at 539 nm overlaps with the absorption of the tetrametrylrhodarnine isothiocyante (TRITC), satisfying the requirement of LRET process. Since TRITC molecules are adsorbed on the β-NaYF4:Yb,Er NPs by an electrostatic interaction, the interaction distance is suitable for LRET without any further modulation. The resultant solid LRET system is ready for the further applications for devices.

Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals

Lanthanide ions exhibit unique luminescent properties, including the ability to convert near infrared long-wavelength excitation radiation into shorter visible wavelengths through a process known as photon upconversion. In recent years lanthanide-doped upconversion nanocrystals have been developed as a new class of luminescent optical labels that have become promising alternatives to organic fluorophores and quantum dots for applications in biological assays and medical imaging. These techniques offer low autofluorescence background, large anti-Stokes shifts, sharp emission bandwidths, high resistance to photobleaching, and high penetration depth and temporal resolution. Such techniques also show potential for improving the selectivity and sensitivity of conventional methods. They also pave the way for high throughput screening and miniaturization. This tutorial review focuses on the recent development of various synthetic approaches and possibilities for chemical tuning of upconversion properties, as well as giving an overview of biological applications of these luminescent nanocrystals.

Cascade upconversion of photoluminescence in quantum dot ensembles

We present a theoretical model and Monte Carlo simulation results that naturally explain all the features of the thermally activated photoluminescence upconversion effect [also known as anti-Stokes photoluminescence (ASPL)] observed in ensembles of colloidal semiconductor nanocrystal quantum dots (QDs). The proposed ASPL mechanism includes the following principal ingredients: (i) optical-phonon-assisted absorption of an incident photon in a relatively large dot in the ensemble, (ii) emission of a higher-energy photon from the zero-phonon exciton-polaron state, with an upconversion equal to one optical-phonon energy, and (iii) cascade reabsorption and re-emission processes involving QDs of successively smaller sizes within the sample, rendering the experimentally observed large anti-Stokes shift of the energy of the photon that finally leaves the sample. The results obtained by the Monte Carlo modeling based on the proposed mechanism reproduce all the experimentally observed ASPL trends in colloidal QD solutions.

Photon Upconversion in Homogeneous Fluorescence‐based Bioanalytical Assays

Upconverting phosphors (UCPs) are very attractive reporters for fluorescence resonance energy transfer (FRET)-based bioanalytical assays. The large anti-Stokes shift and capability to convert near-infrared to visible light via sequential absorption of multiple photons enable complete elimination of autofluorescence, which commonly impairs the performance of fluorescence-based assays. UCPs are ideal donors for FRET, because their very narrow-banded emission allows measurement of the sensitized acceptor emission, in principle, without any crosstalk from the donor emission at a wavelength just tens of nanometers from the emission peak of the donor. In addition, acceptor dyes emitting at visible wavelengths are essentially not excited by near-infrared, which further emphasizes the unique potential of upconversion FRET (UC-FRET). These characteristics result in favorable assay performance using detection instrumentation based on epifluorometer configuration and laser diode excitation. Although UC-FRET is a recently emerged technology, it has already been applied in both immunoassays and nucleic acid hybridization assays. The technology is also compatible with optically difficult biological samples, such as whole blood. Significant advances in assay performance are expected using upconverting lanthanide-doped nanocrystals, which are currently under extensive research. UC-FRET, similarly to other fluorescence techniques based on resonance energy transfer, is strongly distance dependent and may have limited applicability, for example in sandwich-type assays for large biomolecules, such as viruses. In this article, we summarize the essentials of UC-FRET, describe its current applications, and outline the expectations for its future potential.

Infrared up-converting phosphors for bioassays

The development of up-converting phosphor reporter particles has added a powerful tool to modern detection technologies. Carefully constructed phosphor reporters have core-shell structures with surface functional groups suitable for standard bio-conjugations. These reporters are chemically stable, possess the unique property of infrared up-conversion, and are readily detected. In contrast to conventional fluorescent reporters, up-converting phosphor particles do not bleach and allow permanent excitation with simultaneous signal integration. A large anti-Stokes shift (up to 500 nm) separates discrete emission peaks from the infrared excitation source. Along with the unmatched contrast in biological specimens due to the absence of autofluorescence upon infrared excitation, up-converting phosphor technology (UPT) has unique properties for highly-sensitive particle-based assays. The production and characteristics of UPT reporter particles as well as their application in various bioassays is reviewed.