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Carbon dots have been gaining attention in the field of nanobiotechnology due to their superior photostability, high water solubility, ease of synthesis and surface functionalization, chemical inertness, low toxicity, and excellent biocompatibility. They also exhibit good two-photon absorption and unique tunable optical properties across a wide range of wavelengths, from ultraviolet to near infrared endowing them with potential for a variety of biological applications. Recently, there has been a growing interest in the synthesis and development of red-emissive two-photon carbon dots. Here we present recent progress in the design requirements for red-emissive two-photon carbon dots, and review current state-of-the-art systems, covering their applications in bioimaging, biosensing, and photothermal and photodynamic therapy. Carbon dots are suitable for a range of biological applications due to their unique physicochemical properties and biological behavior. This Review summarizes research related to the emerging field of red-emissive two-photon carbon dots for bioimaging, biosensing, and phototherapeutic applications.

In recent years, the development of carbon dot-based fluorescent nanoparticles for bioimaging applications has attracted the attention of scientific community. However, the functionality of the majority of these developed fluorescent systems is confined in to the blue-to-green region of the light spectrum, limiting their application as bioimaging agents. Here, we report the facile design and development of highly efficient two-photon excitable red-emissive carbon dots (D-CD) and demonstrate their high performance in bioimaging applications. Our comprehensive study on the effects of synthesis parameters on the photophysical and physicochemical properties of carbon dots demonstrated the importance of precursor selection and consideration of its molecular structure in developing red-emissive carbon dots. The developed D-CD is highly biocompatible and non-toxic, with remarkable photostability in cells under two-photon near-infrared excitation. The present study point to the great potential of D-CD as an efficient bioimaging agent for cellular biolabeling, long-term and real-time cellular imaging, and high-resolution deep-tissue imaging in complex biological systems.

The tissue engineering approach for repair and regeneration has achieved significant progress over the past decades. However, challenges remain in developing strategies to solve the declined or impaired innate cell and tissue regeneration capacity that occurs with aging. Cellular senescence is a key mechanism underlying organismal aging and is responsible for the declined tissue regeneration capacity in the aging population. Therefore, to promote the diminished tissue regeneration ability in the aged population, it is critical to developing a feasible and promising strategy to target senescent cells. Recent advances in nanomaterials have revolutionized biomedical applications ranging from biosensing to bioimaging and targeted drug delivery. In this perspective, we review and discuss the nature and influences of cell-intrinsic and cell-extrinsic factors on reduced regenerative abilities through aging and how nanotechnology can be a therapeutic avenue to sense, rejuvenate, and eliminate senescent cells, thereby improving the tissue regeneration capacity in the aging population.

Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing. Here we show that NMN treatment partially reverses the effects of tumor necrosis factor-alpha (TNF-α) on human primary osteoblasts (HOBs): senescent cell induction, diminished osteogenic differentiation ability, and intracellular NAD+ and NADH levels. Mechanistically, NMN restores the mitochondrial dysfunction in HOBs induced by TNF-α evidenced by increased mitochondrial membrane potential and reduced reactive oxidative species and mitochondrial mass. NMN also increases mitophagy activity by down-regulating P62 expression and up-regulating light chain 3B-II protein expression. In addition, the cell senescence protective effects of NMN on HOBs are mitigated by a mitophagy inhibitor (Bafilomycin A1). In vivo, NMN supplementation attenuates senescent cell induction in growth plates, partially prevents osteoporosis in an ovariectomized mouse model, and accelerates bone healing in osteoporotic mice. We conclude that NMN can be a novel and promising therapeutic candidate to enhance bone fracture healing capacity in the older.

Recently, carbon dots (CDs) have been widely investigated for biological applications in imaging. One-step hydrothermal synthesis is considered to be one of the most promising methods for the synthesis of CDs, due to its simple and rapid manipulation, flexible selection of ingredients, environmentally friendly conditions, and low-cost. A number of synthetic and post-synthetic parameters, including solvent, heating time, dopant quantity, and particle size distribution, play a crucial role in controlling the size and surface structure of CDs, which ultimately have influence on their photophysical and biological behavior. Despite the crucial role of each of these parameters in defining the yield and nature of synthesized CDs, they have not previously been rigorously optimized, particularly with respect to desired biological applications. Herein, we report our comprehensive optimization of the parameters employed for the hydrothermal synthesis of CDs to gain a better understanding of the effect of these parameters on optical properties, cytotoxicity, and cellular uptake efficiency. Furthermore, this work will open up new pathways toward the design of CDs with physiochemical properties tailored for specific biomedical applications such as bioimaging.

Understanding the surface processes (deposition and surface diffusion) that occur at or close to the surface of growing nanoparticles is important for fabricating reproducibly stellated or branched gold nanoparticles with precise control over arm length and spatial orientation of arms around the core. By employing a simple seed-mediated strategy, we investigate the key synthetic variables for precise tuning of in situ surface processes (competition between the deposition and surface diffusion). These variables include the reduction rate of a reaction, the packing density of molecules/ions on the high surface energy facets, and temperature. As a result, the thermodynamically stabilized nanoparticles (cuboctahedron and truncated cube) and kinetic products (cube, concave cube, octapod, stellated octahedron, and rhombic dodecahedron) in different sizes with high quantitative shape yield (> 80%) can be obtained depending on the reduction rate of reaction and the packing density of molecules/ions. With computer simulation, we studied the stability of stellated (branched structure) and non-stellated (non-branched structure) gold nanoparticles at high temperature. We construct a morphology phase diagram by varying different synthetic parameters, illustrating the formation of both stellated and non-stellated gold nanoparticles in a range of reaction conditions. The stellated gold nanoparticles display shape-dependent optical properties and can be self-assembled into highly ordered superstructures to achieve an enhanced plasmonic response. Our strategy can be applied to other metal systems, allowing for the rational design of advanced new stellated metal nanoparticles with fascinating symmetry dependent plasmonic, catalytic, and electronic properties for technological applications.

Carbon dots (CDs)-based nanoparticles have been extensively explored for biological applications in sensing and bioimaging. However, the major translational barriers to CDs for imaging and sensing applications include synthetic strategies to obtain monodisperse CDs with tunable structural, electronic, and optical properties in order to achieve high-resolution deep-tissue imaging, intracellular detection, and sensing of metal ions with high sensitivity down to nanomolar levels. Herein, we report a novel strategy to synthesize and develop a multifunctional nitrogen-doped CDs probe of different sizes using a new combination of carbon and nitrogen sources. Our results show that the structural characteristics (i.e., the surface density of emissive traps and bandgaps levels) depend on the size of the CDs, which ultimately influences their optical properties. This work also demonstrates the development of a two-photon dual-emissive fluorescent multifunctional probes (3-FCDs) by conjugating fluorescein isothiocyanate on the surface of nitrogen-doped CDs. 3-FCDs show excellent near-infrared two-photon excitation ability, single-wavelength excitation, high photostability, biocompatibility, low cytotoxicity, and good cell permeability. Using two-photon fluorescence imaging, our multifunctional probe shows excellent deep-tissue high-resolution imaging capabilities with penetration depth up to 3000 and 280 μm in hydrogel scaffold and pigskin tissue, respectively. The designed probe exhibits ultrasensitivity and specificity toward Fe3+ ions with a remarkable detection limit of 2.21 nM using two-photon excitation. In addition, we also demonstrate the use of multifunctional CDs probe for ultrasensitive exogenous and real-time endogenous sensing of Fe3+ ions and imaging in live fibroblasts with rapid response times for intracellular ferric ion detection.

Designing a two-photon ratiometric pH-sensitive nanoprobe for real time monitoring of intracellular pH in biological environment is of great importance for better understanding the pathogenesis of diseases and the design of intracellular drug delivery-based system. However, the development of such probe remains a challenge. Here, we report for the first time the design and development of the two-photon ratiometric carbon dot-based nanoprobe and demonstrate its capability to monitor and quantify the intracellular cytoplasmic pH value, in real time. The nanoprobe comprised of a fluorescent carbon dot functionalized with a pH-responsive fluorescein dye (FACD). With increasing pH, FACD exhibits a clear ratiometric change in the emission intensity ratio, with sensitivity across a wide pH range in both extracellular and intracellular compartments. FACD is non-toxic to adipose stem cells in cell imaging experimental conditions and exhibits remarkable thermal stability, photostability, and two-photon near-infrared excitation capability. Using real-time dual-channel two-photon confocal microscopy we demonstrate the great potential of FACD as an efficient nanoprobe with high accuracy for the intracellular sensing of pH in living adipose stem cells seeded on either cell-culture dishes or on a 3D printed bioactive scaffold.

Nanoparticles are key vehicles for targeted therapies because they can pass through biological barriers, enter into cells, and distribute within cell structures. We investigated the synthesis of blue and green emissive hexagonal boron nitride quantum dots (hBNQDs) using a liquid-exfoliation technique followed by hydrothermal treatment. A distinct shift from blue to bright-green emission was observed upon surface passivating the dots using poly(ethylene glycol) or PEG200 under the same UV irradiation. The quantum yield of the hBNQDs increased with the surface passivation. Multiplexed imaging was accomplished using the hBNQDs in conjunction with organic dyes. The hBNQDs provided images with distinctive emission wavelengths and fluorescence lifetimes. Although the fluorescence signals of blue- and green-emissive hBNQDs overlap spectrally with those of the emission wavelengths of the organic dyes, the fluorescence lifetime data were resolved temporally using software-based time gates. The blue-emissive hBNQD-...

Carbon based quantum dots find various applications such as imaging, diagnosis and therapeutics due to low toxicity, antibacterial activity, excellent water solubility, and good biocompatibility. However, the UV-blue emission of carbon based quantum dots is unsuited for applications in biomedicine and imaging as the short wavelength lights harm the living cells due to phototoxicity. In the present work, we have synthesised the long wavelength emitting heteroatoms (nitrogen (N) and sulfur (S)) co-doped graphene quantum dots (NS-GQD) via hydrothermal route. These NS-GQD have excitation-wavelength independent photoluminescence with high quantum yield in protonated and neutral forms. The non-covalent interaction of these NS-GQD when studied with a dye rhodamine B (RB) shows evidence of Forster resonance energy transfer (FRET). It has been shown here that the NS-GQD-RB composite exhibits prominent two-photon absorption at near infrared wavelength with a capability of deep-tissue imaging upto 175 µm.

Nanostructured manganese cobaltite spinel oxide (MnCo 2 O 4 ) was successfully synthesized by co-precipitation method. X-ray diffraction (XRD) results revealed that the molar ratio of OH − / NO 3 − = 1.5 in the precipitation stage is more appropriate for achieving MnCo 2 O 4 phase. The results of thermal analysis (TGA/DTA) along with the XRD results revealed that the MnCo 2 O 4 phase remains stable up to 1050 °C. Morphological studies show that by increasing the calcination temperature from 350 to 550 and 1000 °C, morphology of the particles varies from plate-like to quasi spherical and polyhedral shape, respectively. Density and porosity measurement of cold pressed and sintered samples showed that by employing un-calcined powder, a dense sample with 98% of the theoretical density could be obtained at the sintering temperature of 1000 °C. Selected synthesized powders were coated on the AISI 430 ferritic stainless steel coupons and the results demonstrated that using un-calcined powder, leads to the formation of a highly dense and adhesive coating layer due to the very high tendency of un-calcined powder for densification.