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Nanodiamonds (NDs) have unique optical and mechanical characteristics, surface chemistry, extensive surface area and biocompatibility, and they are nontoxic, rendering them suitable for a diverse range of applications. Recently, NDs have received significant attention in nano-biomedical engineering. This review discusses the recent advancement of NDs’ biomedical engineering, historical background, basic introduction to nanoparticles and development. We summarize NDs’ synthesis technique, properties and applications. Two methodologies are used in ND synthesis: bottom-up and top-down. We cover synthesis methods, including detonation, ball milling, laser ablation, chemical vapor deposition (CVD) and high pressure and high temperature (HPHT); discuss the properties of NDs, such as fluorescence and biocompatibility. Due to these properties, NDs have potential applications in biomedical engineering, including bioimaging, biosensing, drug delivery, tissue engineering and protein mimics. Further, it provides an outlook for future progress, development and application of NDs in biological and biomedical areas.

Quantum dots (QDs), a type of semiconductor nanomaterial, have drawn a lot of attention because of their exceptional optical characteristics and prospective uses in biology and medicine. However, the presence of heavy hazardous metals in typical QDs, such as Cd, Pb and Hg, has posed a significant obstacle to their use. Therefore, it is essential to look for a workable substitute that would be nontoxic and have comparable optical characteristics to the traditional QDs. It has been determined that ternary I–III–VI QDs are appropriate substitutes. They emit light in the near-infrared range and have adjustable optical characteristics. They are valuable in a variety of biological applications because of their optical characteristics and can be easily bioconjugated with biomolecules for targeted imaging. Therefore, this review concentrates on the most recent developments in the usage of aqueous CIS QDs in biological, bioconjugated with biomolecules, nanomedical and drug delivery system applications.

Amphiphilic carbazole pyridinium conjugates are synthesized and characterized by IR, ¹H and ${}^{13}$C NMR and ESI-MS spectrometry. The pyridinium group is attached on the 3-position of the carbazole ring and long alkyl chains are linked to the central $N$ atom. The introduction of a pyridinium group afforded water-soluble carbazole derivatives with significant bathochromic shifts in their absorption and emission spectra. As compared to the parent $N$-butylcarbazole compound, carbazole pyridinium conjugates exhibited 50 nm red-shifted absorption maxima. Similarly, the carbazole pyridinium conjugates displayed 143–147 nm red-shifted emission maxima in solution. In addition, large Stokes shifts (5747–7558 cm${}^{-1})$ were observed for the conjugates in solution. The cell penetrable amphiphilic carbazole pyridinium conjugates exhibited cytoplasmic distribution in A549 cells.

Ultra-small and functional copper nanoclusters (Cu NCs) have been extensively used in consumer technologies due to their superior properties. A simple and green way to prepare stable, water-soluble and near-infrared (NIR) Cu NCs by using a reducing agent was reported in this work. Reduced glutathione (GSH) worked as an important scaffold to prevent NCs from aggregating. Since GSH has functional groups such as carboxyl and amino, it can also be used in reducing Cu²⁺ ions. The resulting GSH–Cu NCs with a particle size of 2.5 nm have good dispersibility in aqueous solution, and show NIR emission with a wavelength of 700 nm (quantum yield 0.6%). MC3T3-E1 cells are used as an example in the fluorescence imaging of GSH–Cu NCs. Several promising features including NIR fluorescence, good water-solubility and biocompatibility, bioactive surface and ultra-small size make the GSH–Cu NCs a good probe for cells.

Lanthanide-doped luminescent nanoscale materials have great potential applications in biological researches. Herein, we reported a novel and mild method for one-step synthesis of chitosan/NaGdF₄:Eu³⁺ nanocomposites. The luminescent Eu³⁺ ions and magnetic resonance imaging (MRI) contrast agent Gd³⁺ ions were incorporated to these biocompatible nanocomposites. The resultant nanocomposites exhibited strong fluorescence and attractive magnetic features. The nanocomposites also have pure hexagonal phase with uniform size of about 65 nm. FT-IR spectra revealed that these nanocomposites were successfully coated by hydrophilic chitosan, whose amine groups conferred the nanocomposites excellent dispensability in aqueous solution. Besides, the MTT assay and laser confocal microscopy images have confirmed the good biocompatibility of the nanocomposites. These results indicated that the as-prepared nanocomposites could be used as an excellent targeted imaging agent in biological fields.

Highly-dispersed graphene nanodots (GNDs) up to 10nm are synthesized using D-galactose as a carbon precursor. The GNDs are self-passivized, emit dual-color excitation-dependent emission and highly biocompatible in cell lines. Their applicability is demonstarted for cellular bioimaging and Raman mapping of cells. Furthermore, their implications on mammalian cell growth and plant seed germination are expounded.

Among the several types of inorganic nanoparticles available, silica nanoparticles (SNP) have earned their relevance in biological applications namely, as bioimaging agents. In fact, fluorescent SNP (FSNP) have been explored in this field as protective nanocarriers, overcoming some limitations presented by conventional organic dyes such as high photobleaching rates. A crucial aspect on the use of fluorescent SNP relates to their surface properties, since it determines the extent of interaction between nanoparticles and biological systems, namely in terms of colloidal stability in water, cellular recognition and internalization, tracking, biodistribution and specificity, among others. Therefore, it is imperative to understand the mechanisms underlying the interaction between biosystems and the SNP surfaces, making surface functionalization a relevant step in order to take full advantage of particle properties. The versatility of the surface chemistry on silica platforms, together with the intrinsic hydrophilicity and biocompatibility, make these systems suitable for bioimaging applications, such as those mentioned in this review.

Upconversion nanoparticles (UCNPs) as a promising material are widely studied due to their unique optical properties. The material can be excited by long wavelength light and emit visible wavelength light through multiphoton absorption. This property makes the particles highly attractive candidates for bioimaging and therapy application. This review aims at summarizing the synthesis and modification of UCNPs, especially the applications of UCNPs as a theranostic agent for tumor imaging and therapy. The biocompatibility and toxicity of UCNPs are also further discussed. Finally, we discuss the challenges and opportunities in the development of UCNP-based nanoplatforms for tumor imaging and therapy.

Fluorescence lifetime imaging (FLIM) is an effective noninvasive bioanalytical tool based on measuring fluorescent lifetime of fluorophores. A growing number of FLIM studies utilizes genetically engineered fluorescent proteins targeted to specific subcellular structures to probe local molecular environment, which opens new directions in cell science. This paper highlights the unconventional applications of FLIM for studies of molecular processes in diverse organelles of live cultured cells.

Black phosphorus (BP) or phosphorene, a new superstar among two-dimensional (2D) materials, has sparked huge scientific interest since its discovery in 2014. BP offers unique characteristics including high drug loading efficiency, excellent photodynamic and photothermal properties and good biocompatibility. These characteristics expand versatility of BP in nanomedicine. Although the outlook of BP seems promising, its practical biomedical applications are still at the very initial stage especially in comparison to other thoroughly investigated inorganic nanomaterials. This paper reviews BP structure and properties as well as its preparation approaches with the emphasis on techniques to improve BP stability and biocompatibility for their further usage in physiological environment. Meanwhile, recent progress made in various biomedical research fields from bioimaging to biosensing is discussed. Last, but not least, current challenges and prospects for BP in biomedicine are briefly examined, which will be useful to guide future developments of BP.

Metal clusters have attracted wide interests due to their unique electronic and optical properties, but the low luminescence quantum yield (QY) prevents them from potential biomedical applications. In this work, silver-doped Au nanoclusters (NCs) are shown to be able to improve the QY of metal clusters. We succeeded in synthesizing ultrabright glutathione (GSH) protected AuAg clusters with 10.8% QY by a one-pot route. Their florescence is about 7.5 times brighter than pure Au NCs, with super photostability and good biocompatibility in physiological environment. Based on density functional theory (DFT) calculations, we investigated the electronic structures and optical properties of the AuAg NCs. The results show that the increase of the density of states of the lowest unoccupied molecular orbital (LUMO) leads to the fluorescence enhancement. In addition, two-photon excitation fluorescence imaging has been performed to show their great potential for biomedicine.

Promising biomedical applications of hybrid materials composed of gold nanoparticles and nucleic acids have attracted strong interest from the nanobiotechnological community. The particular interest is owing to the robust and easy-to-make synthetic approaches, to the versatile optical and catalytic properties of gold nanoparticles combined with the molecular recognition and programmable properties of nucleic acids. The significant progress is made in the development of DNA–gold nanostructures and their applications, such as molecular recognition, cell and tissue bioimaging, targeted delivery of therapeutic agents, etc. This review is focused on the critical discussion of the recent applications of the gold nanoparticles–nucleic acids hybrids. The effect of particle size, surface, charge and thermal properties on the interactions with functional nucleic acids is discussed. For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Emphasis is placed on the systematization of data over the theranostic systems on the basis of the gold nanoparticles–nucleic acids hybrids. Specifically, we start our discussion with observation of the recent data on interaction of various gold nanoparticles with nucleic acids. Further we describe existing gene delivery systems, nucleic acids detection, and bioimaging technologies. Finally, we describe the phenomenon of the polymerase chain reaction improvement by gold nanoparticle additives and its potential underlying mechanisms. Lastly, we provide a short summary of reported data and outline the challenges and perspectives.

Peroxynitrite (ONOO${}^{-})$ contributes to oxidative stress and neurodegeneration in Parkinson’s disease (PD). Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO⁻ flux and understanding of the ONOO⁻ stress-induced neuropathology of PD. Herein, a novel $\alpha$-ketoamide-based fluorogenic probe ( DFlu) was designed for ONOO⁻ monitoring in multiple PD models. The results demonstrated that DFlu exhibits a fluorescence turn-on response to ONOO⁻ with high specificity and sensitivity. The efficacy of DFlu for intracellular ONOO⁻ imaging was demonstrated systematically. The results showed that DFlu can successfully visualize endogenous and exogenous ONOO⁻ in cells derived from chemical and biochemical routes. More importantly, the two-photon excitation ability of DFlu has been well demonstrated by monitoring exogenous/endogenous ONOO⁻ production and scavenging in live zebrafish PD models. This work provides a reliable and promising $\alpha$-ketoamide-based optical tool for identifying variations of ONOO⁻ in PD models.

In this paper, we demonstrate multifunctional upconversion nanoparticles with intense near-infrared emission and unique magnetic properties for dual-modal upconversion luminescent bioimaging and T₂-weighted magnetic resonance imaging. High-quality BaYbF₅:Tm³⁺ nanoparticles are synthesized via a hydrophobic method and then converted to be hydrophilic via a hydrochloric acid treatment. The as-synthesized nanoparticles are cubic phase and about 6 nm in diameter with narrow size distribution. The intense near-infrared emission makes these nanoparticles can be acted as bio-probes in upconversion luminescent bioimaging with deep tissue penetration. Besides, these nanoparticles can also be used as T₂-weighted contrast agents in magnetic resonance imaging due to the high value of relaxation rate (r₂ = 4.05) in 0.55 T. This finding may have further bio-applications in the future due to the high performance of these BaYbF₅:Tm³⁺ nanoparticles in dual-modal bioimaging.

Recent advances in nanotechnology have enabled the synthesis and characterization of nanomaterials suitable for applications in the field of biology and medicine. Due to their unique physico-chemical properties, carbon-based nanomaterials such as fullerenes, metallofullerenes, carbon nanotubes and graphene have been widely investigated as multifunctional materials for applications in tissue engineering, molecular imaging, therapeutics, drug delivery and biosensing. In this review, we focus on the multifunctional capabilities of fullerenes and metallofullerenes for diagnosis and therapy. Specifically, we review recent advances toward the development of fullerene- and metallofullerene-based magnetic resonance imaging (MRI) and X-ray imaging contrast agents, drug and gene delivery vehicles, and photodynamic therapy agents. We also discuss in vitro and in vivo toxicity, and biocompatibility issues associated with the use of fullerenes and metallofullerenes for biomedical applications.

A new type of Cy5-encapsulated photostable fluorescent silica nanoparticles (FSNPs) bearing positive charges have been successfully fabricated by a reverse microemulsion synthesis in one-pot. The Cy5 dye containing four primary amines are embedded into silica via covalent bonds through a silane coupling agent (GPTMS), followed by co-condensation with tetraethylorthosilicate. The uniform-sized, spherical and monodispersed FSNPs have high fluorescence intensity and photostability. The FSNPs exhibit high stability, good biocompatibility as well as low cytotoxicity. These FSNPs can be internalized into live cells and thus fluorescently label the cells. This study provides a simple synthesis approach that can be applied to other water-soluble and amino-modified organic dye molecules for biological targeting and fluorescent cell imaging.

The aim of this paper is to outline and discuss novel and promising findings focusing on (i) the synthesis of fluorescent silver nanoclusters (NCs) using DNA as the stabilizing scaffolds, (ii) the origins of fluorescence and (iii) recent applications in biosensing and imaging. By reviewing the recent synthesis methods and applications of DNA-based silver NCs, we hope to demonstrate that these novel nanolights have the potential to be successful in biomedicine beyond their typically envisioned purposes.

With the rise of graphene, there is growing attention on two-dimensional (2D) materials in the physical science community during the last decade. Most studies to date focus on the rich set of their superior electrical, optical, catalytic and electrochemical properties and highlight the encouraging opportunities for developing next generation electronics, optoelectronics, catalysis, and energy storage technologies. On the contrary, the biomedicine community has barely recognized the potential of these materials other than graphene. There are very limited published studies on these materials’ biological effects and biomedical applications. Here, we present a brief overview of 2D materials and discuss their potential for biomedical applications in hope of raising biomedical researchers’ awareness of the great opportunities associated with these materials. We first discuss the emergence of 2D materials and review two most important prerequisites for 2D materials’ biomedical applications, synthesis and biocompatibility. We then categorize the existing studies on 2D materials’ biomedical applications into biosensing, drug/gene delivery, antimicrobial, bioimaging and multimode therapeutic applications. We would put special emphasis on the great flexibility of various rational combinations of 2D material superior properties for the design and construction of assorted forms of reagents or devices with highly effective simultaneous diagnostic and therapeutic functions (or theranostics functions). At last, the newly emerging 2D black phosphorous with very rare and interesting properties is introduced as the next promising and important 2D materials to study in the upcoming years.

Graphene and graphene-based nanomaterials such as graphene oxide (GO), reduced graphene oxide (rGO) and graphene quantum dots (GQDs) have gained a lot of attention from diverse scientific fields for applications in sensing, catalysis, nanoelectronics, material engineering, energy storage and biomedicine due to its unique structural, optical, electrical and mechanical properties. Graphene-based nanomaterials emerge as a novel class of nanomedicine for cancer therapy for several reasons. Firstly, its structural properties like high surface area and aromaticity enables easy loading of hydrophobic drugs. Secondly, presence of oxygen containing functional groups improve its physiological stability and also act as site for biofunctionalization. Thirdly, its optical absorption in the NIR region enable them to act as photoagents for photothermal and photodynamic therapies of cancer, both in vitro and in vivo. Finally, its intrinsic fluorescence property helps in bioimaging of cancer cells. Overall, graphene-based nanomaterials can act as agents for developing multifunctional theranostic platforms for carrying out more efficient detection and treatment of cancers. This review provides a detailed summary of the different applications of graphene-based nanomaterials in drug delivery, nucleic acid delivery, phototherapy, bioimaging and theranostics.