This Review covers recent progress on near-infrared fluorescence imaging for preclinical animal studies and clinical diagnostics and interventions.

Near-infrared fluorophores for biomedical imaging

The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of the current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities for ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatments.

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Metal-organic frameworks (MOFs), also known as coordination polymers, represent an interesting type of solid crystalline materials that can be straightforwardly self-assembled through the coordination of metal ions/clusters with organic linkers. Owing to the modular nature and mild conditions of MOF synthesis, the porosities of MOF materials can be systematically tuned by judicious selection of molecular building blocks, and a variety of functional sites/groups can be introduced into metal ions/clusters, organic linkers, or pore spaces through pre-designing or post-synthetic approaches. These unique advantages enable MOFs to be used as a highly versatile and tunable platform for exploring multifunctional MOF materials. Here, the bright potential of MOF materials as emerging multifunctional materials is highlighted in some of the most important applications for gas storage and separation, optical, electric and magnetic materials, chemical sensing, catalysis, and biomedicine.

Emerging Multifunctional Metal-Organic Framework Materials.

The synthesis of lanthanide-activated phosphors is pertinent to many emerging applications, ranging from high-resolution luminescence imaging to next-generation volumetric full-color display. In particular, the optical processes governed by the 4f-5d transitions of divalent and trivalent lanthanides have been the key to enabling precisely tuned color emission. The fundamental importance of lanthanide-activated phosphors for the physical and biomedical sciences has led to rapid development of novel synthetic methodologies and relevant tools that allow for probing the dynamics of energy transfer processes. Here, we review recent progress in developing methods for preparing lanthanide-activated phosphors, especially those featuring 4f-5d optical transitions. Particular attention will be devoted to two widely studied dopants, Ce3+ and Eu2+. The nature of the 4f-5d transition is examined by combining phenomenological theories with quantum mechanical calculations. An emphasis is placed on the correlation of hos...

Lanthanide-Activated Phosphors Based on 4f-5d Optical Transitions: Theoretical and Experimental Aspects.

Over the past decade, we have seen rapid advances in applying nanotechnology in biomedical areas including bioimaging, biodetection, and drug delivery. As an emerging field, DNA nanotechnology offers simple yet powerful design techniques for self-assembly of nanostructures with unique advantages and high potential in enhancing drug targeting and reducing drug toxicity. Various sequence programming and optimization approaches have been developed to design DNA nanostructures with precisely engineered, controllable size, shape, surface chemistry, and function. Potent anticancer drug molecules, including Doxorubicin and CpG oligonucleotides, have been successfully loaded on DNA nanostructures to increase their cell uptake efficiency. These advances have implicated the bright future of DNA nanotechnology-enabled nanomedicine. In this review, we begin with the origin of DNA nanotechnology, followed by summarizing state-of-the-art strategies for the construction of DNA nanostructures and drug payloads delivered ...

DNA Nanotechnology-Enabled Drug Delivery Systems

Lanthanide Nanoparticles: From Design toward Bioimaging and Therapy

Rare earth nanomaterials, which feature long-lived intermediate energy levels and intraconfigurational 4f-4f transitions, are promising supporters for photon upconversion. Owing to their unique optical properties, rare earth upconversion nanomaterials have found applications in bioimaging, theranostics, photovoltaic devices, and photochemical reactions. Here, we review recent advances in the photon upconversion processes of these nanomaterials. We start by considering energy transfer models involved in the study of upconversion emissions, as well as well-established synthesis strategies to control the size and shape of rare earth upconversion nanomaterials. Progress in engineering energy transfer pathways, which play a dominant role in determining upconversion emission outputs, is then discussed. Lastly, representative optical applications of these materials are considered. The aim of this review is to provide inspiration for researchers to explore novel upconversion nanomaterials and extended optical applications.

Upconversion of Rare Earth Nanomaterials

Lanthanide-doped luminescent nanoparticles with both emission and excitation in the near-infrared (NIR-to-NIR) region hold great promise for bioimaging. Herein, core@shell structured LiLuF4:Nd@LiLuF4 (named as Nd@Lu) nanoparticles (NPs) with highly efficient NIR emission were developed for high-performance in vivo bioimaging. Strikingly, the absolute quantum yield of Nd@Lu NPs reached as high as 32%. After coating with polyethylene glycol (PEG), the water-dispersible Nd@Lu NPs showed good bio-compatibility and low toxicity. With efficient NIR emission, the Nd@Lu NPs were clearly detectable in tissues at depths of up to 20 mm. In addition, long-term in vivo biodistribution with a high signal-to-noise ratio of 25.1 was distinctly tracked upon an ultralow-power-density excitation (10 mW cm-2) of 732 nm for the first time.

Ultralow-power near-infrared excited neodymium-doped nanoparticles for long-term in vivo bioimaging

Janus particles, in which two distinct compositions are integrated, have attracted considerable interest for their potential multi-functionalities and synergistic effects. Although seed-mediated growth appears to be a suitable strategy that meets the stringent specifications for obtaining Janus particles, it is inapplicable to guide the growth of two crystalline components with different crystal structures. Herein, the formation of Janus particles via phase segregation is proposed. As proof-of-concept, promising photon conversion materials, ScF3 and lanthanide (Ln) fluorides, with great differences in structure, were chosen to build a series of Janus particles. Interestingly, using heavy (Lu, Yb, Dy and Tb) and light (Pr, Nd, Sm, Eu and Gd) lanthanides, ScF3–LiLnF4 and ScF3–LnF3 were formed, respectively. Time-dependent reaction studies indicate that phase segregation paves the way for the formation of these Janus nanoparticles (NPs), and this speculation is further confirmed by in situ transmission electron microscopy observations. These investigations provide new insights for the synthesis of heterostructured materials.

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Phase segregation enabled scandium fluoride–lanthanide fluoride Janus nanoparticles

Rare earths (RE) refer to the lanthanide elements La–Lu together with Sc and Y. Conventionally, they have found applications in phosphors, magnets, catalysts, fuel cell electrodes/electrolyte. Here in this chapter, we discuss the synthesis, assembly and applications of rare earth based anisotropic nanomaterials. Regarding synthesis, the anisotropic growth behaviors of these nanocrystals are predominantly governed by their own unique crystal structures. Yet for wet-chemistry synthetic methods where a number of parameters could be finely tuned, the addition of particular coordination agents, templating agents or mineralizers has proven to be an effective way to direct the growth of nanocrystals into some anisotropic structures. Regarding applications, anisotropic nanomaterials, compared to their isotropic counterparts, often exhibit distinct properties. For example, the luminescence of anisotropic nanomaterials can display polarization and site-specific features. As for rare earth nanomaterials as magnetic resonance imaging (MRI) contrast agents, the high surface area of anisotropic nanostructures can give rise to superior performances. And for catalysis applications, anisotropic nanomaterials expose rich, highly active facets, which is of great importance for facet-selective catalytic reactions. In the chapter, we will start with introduction of the crystal structures of rare earth compounds, then briefly summarize the synthesis and assembly of rare earth anisotropic nanomaterials, and discuss their properties and applications in three realms, namely, luminescence, magnetism and catalysis.

Pei-Zhi Zhang

Papers

Lanthanide Nanoparticles: From Design toward Bioimaging and Therapy

Upconversion of Rare Earth Nanomaterials

Ultralow-power near-infrared excited neodymium-doped nanoparticles for long-term in vivo bioimaging

Phase segregation enabled scandium fluoride–lanthanide fluoride Janus nanoparticles

Rare Earth Based Anisotropic Nanomaterials: Synthesis, Assembly, and Applications