The principles of the design of responsive luminescent probes and sensors based on lanthanide emission are summarised, based on a mechanistic understanding of their mode of action. Competing kinetic ...pathways for deactivation of the excited states that occur are described, highlighting the need to consider each of the salient quenching processes. Such an analysis dictates the choice of both the ligand and its integral sensitising moiety for the particular application. The key aspects of quenching involving electron transfer and vibrational and electronic energy transfer are highlighted and exemplified. Responsive systems for pH, pM, pX and pO
2
and selected biochemical analytes are distinguished, according to the nature of the optical signal observed. Signal changes include both simple and ratiometric intensity measurements, emission lifetime variations and the unique features associated with the observation of circularly polarised luminescence (CPL) for chiral systems. A classification of responsive lanthanide probes is introduced. Examples of the operation of probes for reactive oxygen species, citrate, bicarbonate, α
1
-AGP and pH are used to illustrate reversible and irreversible transformations of the ligand constitution, as well as the reversible changes to the metal primary and secondary coordination sphere that sensitively perturb the ligand field. Finally, systems that function by modulation of dynamic quenching of the ligand or metal excited states are described, including real time observation of endosomal acidification in living cells, rapid urate analysis in serum, accurate temperature assessment in confined compartments and high throughput screening of drug binding to G-protein coupled receptors.
The design principles that guide the creation of responsive lanthanide luminescent probes are defined, classified and exemplified.
Reported immunoadjuvants still have many limitations, such as inferior cellular uptake capacity and biocompatibility, overly large particle sizes, single function, and unsatisfactory therapeutic ...efficacy. Here, large‐pore mesoporous‐silica‐coated upconversion nanoparticles (UCMSs) with a size of less than 100 nm are successfully prepared by a typical silica sol–gel reaction using mesitylene as a pore‐swelling agent and are applied as a novel immunoadjuvant. The obtained UCMSs not only show significantly higher loadings for the photosensitizers merocyanine 540 (MC540), model proteins (chicken ovalbumin (OVA)), and tumor antigens (tumor cell fragment (TF)), but also are successfully employed for highly efficient in vivo vaccine delivery. The prepared UCMSs–MC540–OVA under 980 nm near‐infrared irradiation shows the best synergistic immunopotentiation action, verified by the strongest Th1 and Th2 immune responses and the highest frequency of CD4+, CD8+, and effector‐memory T cells. Additionally, nanovaccines UCMSs–MC540–TF can more effectively inhibit tumor growth and increase the survival of colon cancer (CT26)‐tumor‐bearing BALB/c mice compared with either photodynamic therapy or immunological therapy alone, suggesting the enhanced immunotherapy efficacy and clinical potential of UCMSs as immunoadjuvants for cancer immunotherapy.
Monodispersed large‐pore mesoporous‐silica‐coated β‐NaYF4:20%Yb,2%Er upconversion nanoparticles (UCMSs) as multifunctional immunoadjuvants are prepared by a typical silica sol–gel reaction using mesitylene as a pore‐swelling agent. By mixing with merocyanine 540 (MC540) and tumor cell fragment (TF), the obtained nanovaccine UCMSs–MC540–TF exhibits excellent effects of photodynamic immunotherapy.
Gadolinium(III) complexes have been widely utilised as magnetic resonance imaging (MRI) contrast agents for decades. In recent years however, concerns have developed about their toxicity, believed to ...derive from demetallation of the complexes in vivo, and the relatively large quantities of compound required for a successful scan. Recent efforts have sought to enhance the relaxivity of trivalent gadolinium complexes without sacrificing their stability. This review aims to examine the strategic design of ligands synthesised for this purpose, provide an overview of recent successes in gadolinium-based contrast agent development and assess the requirements for clinical translation.
Many treatments of energy transfer (ET) phenomena in current literature employ incorrect arguments and formulae and are not quantitative enough. This is unfortunate because we witness important ...breakthroughs from ET experiments in nanoscience. This review aims to clarify basic principles by focusing upon Förster-Dexter electric dipole-electric dipole (ED-ED) ET. The roles of ET in upconversion, downconversion and the antenna effect are described and the clichés and simple formulae to be avoided in ET studies are highlighted with alternative treatments provided.
Many treatments of energy transfer (ET) phenomena in current literature employ incorrect arguments and formulae and are not quantitative enough.
Tetrapyrrole derivatives such as porphyrins, phthalocyanines, naphthalocyanines, and porpholactones, are highly stable macrocyclic compounds that play important roles in many phenomena linked to the ...development of life. Their complexes with lanthanides are known for more than 60 years and present breath-taking properties such as a range of easily accessible redox states leading to photo- and electro-chromism, paramagnetism, large non-linear optical parameters, and remarkable light emission in the visible and near-infrared (NIR) ranges. They are at the centre of many applications with an increasing focus on their ability to generate singlet oxygen for photodynamic therapy coupled with bioimaging and biosensing properties. This review first describes the synthetic paths leading to lanthanide-tetrapyrrole complexes together with their structures. The initial synthetic protocols were plagued by low yields and long reaction times; they have now been replaced with much more efficient and faster routes, thanks to the stunning advances in synthetic organic chemistry, so that quite complex multinuclear edifices are presently routinely obtained. Aspects such as redox properties, sensitization of NIR-emitting lanthanide ions, and non-linear optical properties are then presented. The spectacular improvements in the quantum yield and brightness of Yb
III
-containing tetrapyrrole complexes achieved in the past five years are representative of the vitality of the field and open welcome opportunities for the bio-applications described in the last section. Perspectives for the field are vast and exciting as new derivatizations of the macrocycles may lead to sensitization of other Ln
III
NIR-emitting ions with luminescence in the NIR-II and NIR-III biological windows, while conjugation with peptides and aptamers opens the way for lanthanide-tetrapyrrole theranostics.
Tetrapyrrole derivatives such as porphyrins, phthalocyanines, naphthalocyanines, and porpholactones, are highly stable macrocyclic compounds playing crucial roles in biophotonics and biomedicine and are presently at the centre of stunning new applications.
Intravenous delivery of nanomaterials containing therapeutic agents and various cargos for treating neurological disorders is often constrained by low delivery efficacy due to difficulties in passing ...the blood‐brain barrier (BBB). Nanoparticles (NPs) administered intranasally can move along olfactory and trigeminal nerves so that they do not need to pass through the BBB, allowing non‐invasive, direct access to selective neural pathways within the brain. Hence, intranasal (IN) administration of NPs can effectively deliver drugs and genes into targeted regions of the brain, holding potential for efficacious disease treatment in the central nervous system (CNS). In this review, current methods for delivering conjugated NPs to the brain are primarily discussed. Distinctive potential mechanisms of therapeutic nanocomposites delivered via IN pathways to the brain are then discussed. Recent progress in developing functional NPs for applications in multimodal bioimaging, drug delivery, diagnostics, and therapeutics is also reviewed. This review is then concluded by discussing existing challenges, new directions, and future perspectives in IN delivery of nanomaterials.
Intranasal delivery of nanomaterials containing therapeutic agents to the brain is considered a safe, effective, and non‐invasive method. Functionalized nanomaterials with their cargo will move along the olfactory and trigeminal nerves and bypass the blood‐brain barrier entirely. In this article, current methods for delivering functionalized nanomaterials to the brain are described and major mechanisms of therapeutic nanocomposites are discussed.
Half a century after its initial emergence, lanthanide photonics is facing a profound remodeling induced by the upsurge of nanomaterials. Lanthanide‐doped nanomaterials hold promise for ...bioapplications and photonic devices because they ally the unmatched advantages of lanthanide photophysical properties with those arising from large surface‐to‐volume ratios and quantum confinement that are typical of nanoobjects. Cutting‐edge technologies and devices have recently arisen from this association and are in turn promoting nanophotonic materials as essential tools for a deeper understanding of biological mechanisms and related medical diagnosis and therapy, and as crucial building blocks for next‐generation photonic devices. Here, the recent progress in the development of nanomaterials, nanotechnologies, and nanodevices for clinical uses and commercial exploitation is reviewed. The candidate nanomaterials with mature synthesis protocols and compelling optical uniqueness are surveyed. The specific fields that are directly driven by lanthanide doped nanomaterials are emphasized, spanning from in vivo imaging and theranostics, micro‐/nanoscopic techniques, point‐of‐care medical testing, forensic fingerprints detection, to micro‐LED devices.
Lanthanide doped nanomaterials are promising light transducers, integrating the features originating from lanthanide electronic behaviors and nanoscale size effects. Cutting‐edge technologies and devices have recently arisen from this association and are in turn promoting nanomaterials for diverse high‐technology applications. Here, recent progress in developing lanthanide‐containing nanomaterials, nanotechnologies, and nanodevices for clinical employment use and commercial exploitation is reviewed.
The optical thermometer has shown great promise for use in the fields of aeronautical engineering, environmental monitoring and medical diagnosis. Self-referencing lanthanide thermo-probes ...distinguish themselves because of their accuracy, calibration, photostability, and temporal dimension of signal. However, the use of conventional lanthanide-doped materials is limited by their poor reproducibility, random distance between energy transfer pairs and interference by energy migration, thereby restricting their utility. Herein, a strategy for synthesizing hetero-dinuclear complexes that comprise chemically similar lanthanides is introduced in which a pair of thermosensitive dinuclear complexes, cycTb-phEu and cycEu-phTb, were synthesized. Their structures were geometrically optimized with an internuclear distance of approximately 10.6Å. The sensitive linear temperature-dependent luminescent intensity ratios of europium and terbium emission over a wide temperature range (50-298K and 10-200K, respectively) and their temporal dimension responses indicate that both dinuclear complexes can act as excellent self-referencing thermometers. The energy transfer from Tb
to Eu
is thermally activated, with the most important pathway involving the
F
Eu
-multiplet at room temperature. The energy transfer from the antenna to Eu
was simulated, and it was found that the most important ligand contributions to the rate come from transfers to the Eu
upper states rather than direct ligand-metal transfer to
D
or
D
. As the first molecular-based thermometer with clear validation of the metal ratio and a fixed distance between the metal pairs, these dinuclear complexes can be used as new materials for temperature sensing and can provide a new platform for understanding the energy transfer between lanthanide ions.
Frequency‐upconverted fluorescence and stimulated emission induced by multiphoton absorption (MPA) have attracted much interest. As compared with low‐order MPA processes, the construction of ...high‐order MPA processes is highly desirable and rather attractive, yet remains a formidable challenge due to its inherent low transition probability. We report the observation of the first experimental frequency‐upconverted fluorescence and stimulated emission by simultaneous six‐photon excitation in an organic molecular system. The well‐designed organic conjugated system based on cross‐shaped spiro‐fused ladder‐type oligo(p‐phenylene)s (SpL−z, z=1–3) manifests reasonably high MPA cross‐sections and brilliant luminescence emission simultaneously. The six‐photon absorption cross‐section of SpL‐3 with an extended π‐conjugation was evaluated as 8.67×10−169 cm12 s5 photon−5. Exceptionally efficient 2‐ to 6‐photon excited stimulated emission was achieved under near‐infrared laser excitation.
Efficient frequency‐upconverted fluorescence and stimulated emission have been demonstrated in spiro‐fused ladder‐type oligo(p‐phenylene)s through multiphoton absorption with an absorbed photon number up to six. The results demonstrate an effective molecular design strategy for exploring highly efficient MPA fluorophores for multiphoton optical applications.
Near-infrared （NIR） persistent-luminescence nanoparticles have emerged as a new class of background-free contrast agents that are promising for in vivo imaging. The next key roadblock is to establish ...a robust and controllable method for synthesizing monodisperse nanoparticles with high luminescence brightness and long persistent duration. Herein, we report a synthesis strategy involving the coating/etching of the SiO2 shell to obtain a new class of small NIR highly persistent luminescent ZnGa2O4：Cr^3＋,Sn^4＋（ZGOCS） nanoparticles. The optimized ZGOCS nanoparticles have an excellent size distribution of -15 nm without any agglomeration and an NIR persistent luminescence that is enhanced by a factor of 13.5, owing to the key role of the SiO2 shell in preventing nanoparticle agglomeration after annealing. The ZGOCS nanoparticles have a signal-to-noise ratio -3 times higher than that of previously reported ZnGa204：Cr^3＋ （ZGC-1） nanoparticles as an NIR persistent-luminescence probe for in vivo bioimaging. Moreover, the persistent-luminescence signal from the ZGOCS nanoparticles can be repeatedly re-charged in situ with external excitation by a white light- emitting diode; thus, the nanopartides are suitable for long-term in vivo imaging applications. Our study suggests an improved strategy for fabricating novel high-performance optical nanoparticles with good biocompatibility.
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