Metal-halide perovskites have rapidly emerged as one of the most promising materials of the 21st century, with many exciting properties and great potential for a broad range of applications, from photovoltaics to optoelectronics and photocatalysis. The ease with which metal-halide perovskites can be synthesized in the form of brightly luminescent colloidal nanocrystals, as well as their tunable and intriguing optical and electronic properties, has attracted researchers from different disciplines of science and technology. In the last few years, there has been a significant progress in the shape-controlled synthesis of perovskite nanocrystals and understanding of their properties and applications. In this comprehensive review, researchers having expertise in different fields (chemistry, physics, and device engineering) of metal-halide perovskite nanocrystals have joined together to provide a state of the art overview and future prospects of metal-halide perovskite nanocrystal research.

State of the Art and Prospects for Halide Perovskite Nanocrystals.

Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and found that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, suggesting that glutamine's ability to replenish tricarboxylic acid cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis.

Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells

The past decade has witnessed tremendous advances in synthesis of metal halide perovskites and their use for a rich variety of optoelectronics applications. Metal halide perovskite has the general formula ABX3, where A is a monovalent cation (which can be either organic (e.g., CH3NH3+ (MA), CH(NH2)2+ (FA)) or inorganic (e.g., Cs+)), B is a divalent metal cation (usually Pb2+), and X is a halogen anion (Cl-, Br-, I-). Particularly, the photoluminescence (PL) properties of metal halide perovskites have garnered much attention due to the recent rapid development of perovskite nanocrystals. The introduction of capping ligands enables the synthesis of colloidal perovskite nanocrystals which offer new insight into dimension-dependent physical properties compared to their bulk counterparts. It is notable that doping and ion substitution represent effective strategies for tailoring the optoelectronic properties (e.g., absorption band gap, PL emission, and quantum yield (QY)) and stabilities of perovskite nanocrystals. The doping and ion substitution processes can be performed during or after the synthesis of colloidal nanocrystals by incorporating new A', B', or X' site ions into the A, B, or X sites of ABX3 perovskites. Interestingly, both isovalent and heterovalent doping and ion substitution can be conducted on colloidal perovskite nanocrystals. In this review, the general background of perovskite nanocrystals synthesis is first introduced. The effects of A-site, B-site, and X-site ionic doping and substitution on the optoelectronic properties and stabilities of colloidal metal halide perovskite nanocrystals are then detailed. Finally, possible applications and future research directions of doped and ion-substituted colloidal perovskite nanocrystals are also discussed.

Doping and ion substitution in colloidal metal halide perovskite nanocrystals.

Phototherapy such as photothermal therapy and photodynamic therapy in cancer treatment has been developed quickly over the past few years for its noninvasive nature and high efficiency. However, there are still many drawbacks in phototherapy that prevent it from clinical applications. Thus, scientists have designed different systems to overcome the issues associated with phototherapy, including enhancing the targeting ability of phototherapy, low-temperature photothermal therapy, replacing near-infrared light with other excitation sources, and so on. This article discusses the problems and shortcomings encountered in the development of phototherapy and highlights possible solutions to address them so that phototherapy may become a useful cancer treatment approach in clinical practice. This article aims to give a brief summary about current research advancements in phototherapy research and provides a quick guideline toward future developments in the field.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202002504

Solutions to the Drawbacks of Photothermal and Photodynamic Cancer Therapy

Impurity doping is a promising method to impart new properties to various materials. Due to their unique optical, magnetic, and electrical properties, rare-earth ions have been extensively explored as active dopants in inorganic crystal lattices since the 18th century. Rare-earth doping can alter the crystallographic phase, morphology, and size, leading to tunable optical responses of doped nanomaterials. Moreover, rare-earth doping can control the ultimate electronic and catalytic performance of doped nanomaterials in a tunable and scalable manner, enabling significant improvements in energy harvesting and conversion. A better understanding of the critical role of rare-earth doping is a prerequisite for the development of an extensive repertoire of functional nanomaterials for practical applications. In this review, we highlight recent advances in rare-earth doping in inorganic nanomaterials and the associated applications in many fields. This review covers the key criteria for rare-earth doping, including basic electronic structures, lattice environments, and doping strategies, as well as fundamental design principles that enhance the electrical, optical, catalytic, and magnetic properties of the material. We also discuss future research directions and challenges in controlling rare-earth doping for new applications.

Rare-Earth Doping in Nanostructured Inorganic Materials.

The use of X-rays instead of UV/Vis light to trigger photodynamic therapy, named X-ray inducible photodynamic therapy, holds tremendous promise due to a high penetration capacity in tissues and is worthy of in-depth study. In this study, a novel multifunctional nanoagent based on Merocyanine 540-coupled Gd2 (WO4 )3 :Tb nanoscintillators and the vitalization of its abilities for dual-modal computed tomography and the magnetic-resonance-imaging-guided synergistic radio-/X-ray inducible photodynamic therapy of tumors is reported. Synergistic therapies show a higher tumor growth inhibition efficiency at a lower X-ray dose than radiotherapy alone. Through this proof-of-concept work, a way to tactfully understand and utilize nanoscintillators for cancer theranostics is shown.

CT/MRI‐Guided Synergistic Radiotherapy and X‐ray Inducible Photodynamic Therapy Using Tb‐Doped Gd‐W‐Nanoscintillators

Radio- and photodynamic therapies are the first line of cancer treatments but suffer from poor light penetration and less radiation accumulation in soft tissues with high radiation toxicity. Therefore, a multifunctional nanoplatform with diagnosis-assisted synergistic radio- and photodynamic therapy and tools facilitating early prognosis are urgently needed to fight the war against cancer. Further, integrating cancer therapy with untargeted metabolomic analysis would collectively offer clinical pertinence through facilitating early diagnosis and prognosis. Here, we enriched scintillation of CeF3 nanoparticles (NPs) through codoping Tb3+ and Gd3+ (CeF3:Gd3+,Tb3+) for viable clinical approach in the treatment of deep-seated tumors. The codoped CeF3:Gd3+,Tb3+ scintillating theranostic NPs were then coated with mesoporous silica, followed by loading with rose bengal (CGTS-RB) for later computed tomography (CT)- and magnetic resonance image (MRI)-guided X-ray stimulated synergistic radio- and photodynamic therapy (RT+XPDT) using low-dose, one-time X-ray irradiation. The results corroborated an efficient tumor regression with synergistic RT+XPDT relative to single RT. Global untargeted metabolome shifts highlighted the mechanism behind this efficient tumor regression using RT, and synergistic RT+XPDT treatment is due to the starvation of nonessential amino acids involved in protein and DNA synthesis and energy regulation pathways necessary for growth and progression. Our study also concluded that tumor and serum metabolites shift during disease progression and regression and serve as robust biomarkers for early assessment of disease state and prognosis. From our results, we propose that codoping is an effective and extendable technique to other materials for gaining high optical yield and multifunctionality and for use in diagnostic and therapeutic applications. Critically, the integration of multifunctional theranostic nanomedicines with metabolomics has excellent potential for the discovery of early metabolic biomarkers to aid in better clinical disease diagnosis and prognosis.

Codoping Enhanced Radioluminescence of Nanoscintillators for X-ray-Activated Synergistic Cancer Therapy and Prognosis Using Metabolomics

Bright Blue Light‐Emitting Doped Cesium Bromide Nanocrystals: Alternatives of Lead‐Free Perovskite Nanocrystals for White LEDs

Highly sensitive fluorescence-linked immunosorbent assay based on aggregation-induced emission luminogens incorporated nanobeads

Multimodal lateral flow immunoassay (LFIA) has shown promise for improving both the flexibility and practicability of point-of-care test We report here a facile, in situ growth method for preparing multifunctional core-shell-shell nano-sunflowers with a unique combination of color-magnetic-Raman properties The use of Fe3O4 nanobeads with high saturation magnetization as the magnetic core allowed for robust magnetic signal strength-even after successive coatings of polydopamine and gold nanoparticles (Au NPs) Carefully selected 4-mercaptobenzonitrile molecules not only contributed to the growth of the Au NP shell but also generated a strong, surface-enhanced Raman scattering signal The resulting nanomaterials were successfully used in the construction of multimodal LFIA with one qualitative and two alternative quantitative detection modes of different sensitivity levels The limit of detection for the paradigm target-human chorionic gonadotropin-was 10 mIU/mL in color mode, 12 mIU/mL in magnetic mode, and 02 mIU/mL in Raman mode

Xinyi Liu

Papers

CT/MRI‐Guided Synergistic Radiotherapy and X‐ray Inducible Photodynamic Therapy Using Tb‐Doped Gd‐W‐Nanoscintillators

Codoping Enhanced Radioluminescence of Nanoscintillators for X-ray-Activated Synergistic Cancer Therapy and Prognosis Using Metabolomics

Bright Blue Light‐Emitting Doped Cesium Bromide Nanocrystals: Alternatives of Lead‐Free Perovskite Nanocrystals for White LEDs

Highly sensitive fluorescence-linked immunosorbent assay based on aggregation-induced emission luminogens incorporated nanobeads

Multifunctional Nano-Sunflowers with Color-Magnetic-Raman Properties for Multimodal Lateral Flow Immunoassay.