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 increasing demand of clinical biomedicine and fast development of nanobiotechnology has substantially promoted the generation of a variety of organic/inorganic nanosystems for biomedical applications. Biocompatible two-dimensional (2D) graphene analogues (e.g., nanosheets of transition metal dichalcogenides, transition metal oxides, g-C3N4, Bi2Se3, BN, etc.), which are referred to as 2D-GAs, have emerged as a new unique family of nanomaterials that show unprecedented advantages and superior performances in biomedicine due to their unique compositional, structural and physicochemical features. In this review, we summarize the state-of-the-art progress of this dynamically developed material family with a particular focus on biomedical applications. After the introduction, the second section of the article summarizes a range of synthetic methods for new types of 2D-GAs as well as their surface functionalization. The subsequent section provides a snapshot on the use of these biocompatible 2D-GAs for a broad spectrum of biomedical applications, including therapeutic (photothermal/photodynamic therapy, chemotherapy and synergistic therapy), diagnostic (fluorescent/magnetic resonance/computed tomography/photoacoustic imaging) and theranostic (concurrent diagnostic imaging and therapy) applications, especially on oncology. In addition, we briefly present the biosensing applications of these 2D-GAs for the detection of biomacromolecules and their in vitro/in vivo biosafety evaluations. The last section summarizes some critical unresolved issues, possible challenges/obstacles and also proposes future perspectives related to the rational design and construction of 2D-GAs for biomedical engineering, which are believed to promote their clinical translations for benefiting the personalized medicine and human health.

Two-dimensional graphene analogues for biomedical applications.

Semiconductor quantum dots (QDs) have become important fluorescent probes for in vitro and in vivo bioimaging research. Their nanoparticle surfaces for versatile bioconjugation, their adaptable photophysical properties for multiplexed detection, and their superior stability for longer investigation times are the main advantages of QDs compared to other fluorescence imaging agents. Here, we review the recent literature dealing with the design and application of QD-bioconjugates for advanced in vitro and in vivo imaging. After a short summary of QD preparation and their most important properties, different QD-based imaging applications will be discussed from the technological and the biological point of view, ranging from super-resolution microscopy and single-particle tracking over in vitro cell and tissue imaging to in vivo investigations. A substantial part of the review will focus on multifunctional applications, in which the QD fluorescence is combined with drug or gene delivery towards theranostic approaches or with complementary technologies for multimodal imaging. We also briefly discuss QD toxicity issues and give a short outlook on future directions of QD-based bioimaging.

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Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors

Microwave-assisted preparation of inorganic nanostructures in liquid phase.

Biosynthesis and Bioconjugation to Biomedical Application Juan Zhou,‡,§ Yong Yang, and Chun-yang Zhang*,†,§ †College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, China ‡State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China Single-Molecule Detection and Imaging Laboratory, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

Toward Biocompatible Semiconductor Quantum Dots: From Biosynthesis and Bioconjugation to Biomedical Application

Herein, we present a multifunctional chip based on surface-enhanced Raman scattering (SERS) that effectively captures, discriminates, and inactivates pathogenic bacteria. The developed SERS chip is made of a silicon wafer decorated with silver nanoparticles and modified with 4-mercaptophenylboronic acid (4-MPBA). It was prepared in a straightforward manner by chemical reduction assisted by hydrogen fluoride etching, followed by the conjugation of 4-MPBA through AgS bonds. The dominant merits of the fabricated SERS chip include excellent reproducibility with a relative standard deviation (RSD) value smaller than 11.0 %, adaptable bacterial-capture efficiency (ca. 60 %) at low concentrations (500–2000 CFU mL−1), a low detection limit (down to a concentration of 1.0×102 cells mL−1), and high antibacterial activity (an antibacterial rate of ca. 97 %). The SERS chip enabled sensitive and specific discrimination of Escherichia coli and Staphylococcus aureus from human blood.

Simultaneous Capture, Detection, and Inactivation of Bacteria as Enabled by a Surface-Enhanced Raman Scattering Multifunctional Chip†

Protective shell: A microwave-assisted method allows rapid production of biofunctional and fluorescent silicon nanoparticles (SiNPs), which can be used for cell labeling. Such SiNPs feature excellent aqueous dispersibility, are strongly fluorescent, storable, photostable, stable at different pH values, and biocompatible. The method opens new avenues for designing multifunctional SiNPs and related silicon nanostructures.

Microwave-assisted synthesis of biofunctional and fluorescent silicon nanoparticles using proteins as hydrophilic ligands.

Silicon-Nanowire-Based Nanocarriers with Ultrahigh Drug-Loading Capacity for In Vitro and In Vivo Cancer Therapy†

Fluorescent silicon nanoparticles (SiNPs), as the most important zero-dimensional silicon nanostructures, hold high promise for long-awaited silicon-based optic applications. There currently remain major challenges for the green, inexpensive, and mass production of fluorescent SiNPs, resulting in difficulties in sufficiently exploiting the properties of these remarkable materials. Here, we show that fluorescent small-sized (∼3.8 nm) SiNPs can be produced through biomimetic synthesis in rapid (10 min), low-cost, and environmentally benign manners. The as-prepared SiNPs simultaneously feature bright fluorescence (quantum yield (QY), ∼15–20%), narrow emission spectral width (full width at half-maximum (fwhm), ∼30 nm), and nontoxicity, making them as high-quality fluorescent probes for biological imaging in vitro and in vivo.

Biomimetic Preparation and Dual-Color Bioimaging of Fluorescent Silicon Nanoparticles

The development of nanozymes has made active impact in diagnosis and therapeutics. However, understanding of the full effects of these nanozymes on biochemical pathways and metabolic homeostasis remains elusive. Here, it is found that iron oxide nanoparticles (Fe3 O4 NPs), a type of well-established nanozyme, can locally regulate the energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) via their peroxidase-like activity in the acidic lysosomal compartment, thereby promoting glucose metabolism and insulin response. Fe3 O4 NPs induce AMPK activation and enhance glucose uptake in a variety of metabolically active cells as well as in insulin resistant cell models. Dietary Fe3 O4 NPs display therapeutic effects on hyperglycemia and hyperinsulinemia in Drosophila models of diabetes induced by genetic manipulation or high-sugar diet. More importantly, intraperitoneal administration of Fe3 O4 NPs stimulates AMPK activities in metabolic tissues, reduces blood glucose levels, and improves glucose tolerance and insulin sensitivity in diabetic ob/ob mice. The study reveals intrinsic organelle-specific properties of Fe3 O4 NPs in AMPK activation, glycemic control, and insulin-resistance improvement, suggesting their potential efficacy in diabetes care.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/adma.202003708

Yanfeng Zhou

Papers

Simultaneous Capture, Detection, and Inactivation of Bacteria as Enabled by a Surface-Enhanced Raman Scattering Multifunctional Chip†

Microwave-assisted synthesis of biofunctional and fluorescent silicon nanoparticles using proteins as hydrophilic ligands.

Silicon-Nanowire-Based Nanocarriers with Ultrahigh Drug-Loading Capacity for In Vitro and In Vivo Cancer Therapy†

Biomimetic Preparation and Dual-Color Bioimaging of Fluorescent Silicon Nanoparticles

An Organelle-Specific Nanozyme for Diabetes Care in Genetically or Diet-Induced Models.