Bioimaging Applications Research Articles

One Stone, Three Birds: Design and Synthesis of “All-in-One” Nanoscale Mn-Porphyrin Coordination Polymers for Magnetic Resonance Imaging-Guided Synergistic Photodynamic-Sonodynamic Therapy

Multifunctional nanomaterials with potential applications in both bioimaging and photodynamic-sonodynamic therapy have great advantages in cancer theranostic, but the design and preparation of “all-in-one” type of multifunctional nanomaterials with single component remains challenging. Herein the “all-in-one” type of Mn-PpIX (Protoporphyrin IX) coordination polymers (MnPPs) was reported as efficient nano-photo/sonosensitizers. The MnPPs had an average size of ∼ 110 nm. Upon light/US (ultrasound) irradiation for 5 min, 61.8 % (light) and 32.4 % (US) of DPBF (1.3-diphenyl isobenzofuran) was found to be oxidized by MnPPs, which showed effective ROS (reactive oxygen species) generation for photodynamic/sonodynamic therapy (PDT/SDT). In addition, MnPPs revealed excellent biosafety and could be engulfed by cells to produce intracellular ROS under light/US excitation for efficient killing tumor cells. When MnPPs was injected into mice, the tumor could be monitored via MRI (magnetic resonance imaging). In addition, tumor growth could be significantly inhibited by the synergistic PDT-SDT. Therefore, the present study not only represents MnPPs as an “all-in-one” type of multifunctional nanomaterials for MRI-guided PDT-SDT therapy, but also provides some insights for designing other PpIX-related molecules with the similar structure for bioapplication.

Fabrication of high-density nitrogen-vacancy (NV) center-enriched diamond particles through methyl trityl amine (C20H19N) seeding

Diamond particles (DPs) show promise for advanced applications in bioimaging and quantum sensing due to the presence of defect centers. This work reports a unique growth process for diamond particles composed of nitrogen-vacancy centers (NV-DPs) using a methyl trityl amine (C20H19N) diamondoid seed, which acts as a nitrogen source for NV creation. Growth was performed via microwave plasma-assisted chemical vapor deposition in a CH4/H2 plasma. Tantalum plates were chosen as the substrate to facilitate the release of the NV-rich DPs after growth. Raman spectra of NV-DPs grown at 550 °C showed a sharp, intense peak at ∼1334 cm−1, while those grown at 750 °C exhibited a broader, high intensity peak at 1336 cm−1. Photoluminescence revealed the formation of high-density NV centers, with the highest intensity for NV-DPs grown at 750 °C and 20 Torr. Optically detected magnetic resonance confirmed the presence of NV centers, especially for DPs grown at 750 °C. This seeding process enables precise nitrogen incorporation into diamond crystals to generate required spin properties by growing high-quality, well-faceted NV-DPs with customizable NV densities.

Biocidal polymer derived near white light-emitting polymeric carbon particles for antibacterial and bioimaging applications.

A growing antimicrobial crisis has increased demand for antimicrobial materials. It has become increasingly popular to convert polymeric macromolecules into polymeric carbon particles (PCP) in order to achieve highly biocompatible materials with unique properties as a result of the ability to synthesize nanomaterials of the right size and add value to existing stable polymers. This work presents the tuning of PCP for antibacterial application by combining a biocidal polymer with one-pot solvothermal synthesis. PCP displayed broad-spectrum antibacterial activity via various mechanisms, including inhibition of bacterial cell walls, ROS generation, and antibiotic resistance. Furthermore, these biocidal PCP were observed to show excitation-independent near-white light emission which on the other hand is generally possible due to mixed sizes, doping, and surface effects. As opposed to the parent biocidal polymer, PCP added ROS-mediated bactericidal activity, increased cytocompatibility, and nanofibers with anti-adhesive effects and potential of imaging bacterial cells.

CARBON DOTS: Bioimaging and Anticancer Drug Delivery.

Cancer, responsible for approximately 10 million lives annually, urgently requires innovative treatments, as well as solutions to mitigate the limitations of traditional chemotherapy, such as long-term adverse side effects and multidrug resistance. This review focuses on Carbon Dots (CDs), an emergent class of nanoparticles (NPs) with remarkable physicochemical and biological properties, and their burgeoning applications in bioimaging and as nanocarriers in drug delivery systems for cancer treatment. The review initiates with an overview of NPs as nanocarriers, followed by an in-depth look into the biological barriers that could affect their distribution, from barriers to administration, to intracellular trafficking. It further explores CDs' synthesis, including both bottom-up and top-down approaches, and their notable biocompatibility, supported by a selection of in vitro, in vivo, and ex vivo studies. Special attention is given to CDs' role in bioimaging, highlighting their optical properties. The discussion extends to their emerging significance as drug carriers, particularly in the delivery of doxorubicin and other anticancer agents, underscoring recent advancements and challenges in this field. Finally, we showcase examples of other promising bioapplications of CDs, emergent owing to the NPs flexible design. As research on CDs evolves, we envisage key challenges, as well as the potential of CD-based systems in bioimaging and cancer therapy.

Investigations on anticancer activity of Eu3+ doped hydroxyapatite nanocomposites against MCF7 and 4T1 breast cancer cell lines: A structural and luminescence Perspective

Breast cancer remains a significant global health concern, necessitating the development of novel therapeutic approaches. In this study, we investigate the role of Eu3+ doped hydroxyapatite nanocomposites (Han: Eu3+) in the treatment of MCF7 and 4T1 breast cancer cell lines. Furthermore, we explored the structural and luminescent properties of these nanocomposites. Han: Eu3+ were synthesized using a modified co-precipitation method, and their morphology and crystal structure were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) in which the average crystalline size of Han: Eu3+ was found to be 25 nm, rendering them suitable for cellular uptake and targeted therapy. To gain insights into the luminescent properties of Han: Eu3+, their excitation and emission spectra were recorded using photoluminescence spectrometer. The characteristic red emission of Eu3+ ions was observed upon excitation, validating the successful doping of Eu3+ into the Han lattice, which was confirmed by the CIE chromaticity coordinate study. These luminescent properties of Han: Eu3+ hold promise for potential applications in bioimaging. To evaluate the efficacy of Han: Eu3+ in breast cancer treatment, MCF7 and 4T1 cell lines were exposed to varying concentrations of the nanocomposites. Cell viability assays revealed a concentration-dependent reduction in cell viability, indicating the potential anticancer activity of Han: Eu3+. The findings of this study contribute to the expanding field of nanomedicine, bringing targeted breast cancer treatments and us closer to more effective.

Dual Nature of Thiophene Harnessed in the Design of Near-Infrared Emitters via Antiaromaticity Relief.

Near-infrared (NIR) emitters are of great interest for applications in bioimaging and modern technology. Yet the design of such materials with decent characteristics is challenging due to intrinsic limitations. In a recent article, Murai and Yamaguchi report the synthesis of NIR emitters with appreciable fluorescence quantum yields reaching 0.02 at 878 nm in CH2 Cl2 solution. The low band gaps were achieved by a new design strategy exploiting antiaromaticity relief. This concept was realized for compounds consisting of an antiaromatic azepine central ring fused to thiophene moieties. In these systems, thiophene unfolds its dual nature. On the one hand, it contributes to the high antiaromaticity of azepine; on the other hand, it exerts a stabilizing effect on azepine through the formation of a quinoid structure, which reduces its antiaromaticity and shifts the absorption and emission maxima into the NIR region.

Dual Nature of Thiophene Harnessed in the Design of Near‐Infrared Emitters via Antiaromaticity Relief

AbstractNear‐infrared (NIR) emitters are of great interest for applications in bioimaging and modern technology. Yet the design of such materials with decent characteristics is challenging due to intrinsic limitations. In a recent article, Murai and Yamaguchi report the synthesis of NIR emitters with appreciable fluorescence quantum yields reaching 0.02 at 878 nm in CH2Cl2 solution. The low band gaps were achieved by a new design strategy exploiting antiaromaticity relief. This concept was realized for compounds consisting of an antiaromatic azepine central ring fused to thiophene moieties. In these systems, thiophene unfolds its dual nature. On the one hand, it contributes to the high antiaromaticity of azepine; on the other hand, it exerts a stabilizing effect on azepine through the formation of a quinoid structure, which reduces its antiaromaticity and shifts the absorption and emission maxima into the NIR region.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.

Synthesis of graphene quantum dots from Moringa oleifera seed biomass doped with phosphate

In this work, graphene quantum dots (GQDs) were synthesized from Moringa oleifera seed biomass doped with phosphorus, using a low-cost, renewable hydrothermal method. The biomass was ground and sieved (30 mesh), and the classified powder was transferred to a Teflon capsule, placed in a stainless-steel reactor (210 ºC, 24 h). Afterwards, 20 mL of distilled water were added to the synthesized GQDs, stirred for 30 min, and filtered through Whatman filter paper. Then they were centrifuged (12000 rpm, 10 min) and filtered through a 0.22 μm membrane. The filtrate was dialyzed in a cellulose dialysis bag, with a cut-off size of 3.5 kDa, for 7 days in absolute ethanol (99.5%), with gentle stirring, and the dialysate was exchanged every 24 h. The dialysate was dried at 105 ºC for 24 h. The GQDs were characterized by X-ray energy dispersive spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), UV-vis electronic absorption, fluorescence emission, X-ray Diffraction and high-resolution transmission electron microscopy (HRTEM). The results show the GQDs with an average size of 18.63 ± 4.24 nm and high fluorescence (bright blue) under ultraviolet light (365 nm). Our GQDs are promising for application in bioimaging and bioanalysis.

Dynamic Ultra‐long Room Temperature Phosphorescence Enabled by Amorphous Molecular “Triplet Exciton Pump” for Encryption with Temporospatial Resolution

AbstractOrganic ultra‐long room‐temperature phosphorescence (RTP) materials in the amorphous state have attracted widespread attention due to their simple preparation and flexibility to adopt various forms in sensors, bioimaging, and encryption applications. However, the amorphous molecular host for the host–guest RTP systems is highly demanded but limited. Here, a universal molecular host (DPOBP−Br) has been designed by integration of an amorphous moiety of diphenylphosphine oxide (DPO) and an intersystem crossing (ISC) group of 4‐bromo‐benzophenone (BP−Br). Various commercial fluorescence dyes were doped into the tight and transparent DPOBP−Br film, respectively, resulting in amorphous host–guest systems with ultra‐long RTP colors from green to red. It was found that DPOBP−Br acted as a universal “triplet exciton pump” for promoting the generation of triplet excitons in the guest, through energy transfer processes and external heavy‐atom effect based on DPOBP−Br. Interestingly, dynamic RTP was achieved by controlling residual oxygen concentration in the amorphous matrix by UV irradiation. Therefore, multi‐dimensional anti‐counterfeiting coatings were realized even on curved surfaces, simultaneously exhibiting spatial and 2D‐time dependence. This work provides a strategy to design new amorphous molecular hosts for RTP systems and demonstrates the advanced information encryption with tempo‐spatial resolution based on the dynamic ultra‐long RTP of an amorphous system.

A novel fluorescent probe for cascade detection of hydrogen sulfide and hypochlorous acid and its application in bioimaging

Herein we developed a cascade detection mode for the detection of HS− and ClO− by the novel probe NM-Cl bearing a conjugating naphthalene-dicyanoisophorone unit. The probe displayed sensitive and remarkable fluorescent enhancement in response to HS−, but not to other analytes. The mixture of probe and HS− constructed a specific sensing system for ClO− by fluorescent quenching response. The mechanism studies indicated that the successive reacting of HS− substitution Cl atom in probe and then addition of ClO− facilitation a thiofuran ring-forming induced differentiated fluorescence emission. This study provides a novel mechanism for the detection of HS− and ClO−, the imaging of cell and living animal further indicating the good application prospects of the probe in biosensing and bioimaging.

Synthesis of an aggregation-induced emission (AIE) dye with pH-sensitivity based on tetraphenylethylene-pyridine for fluorescent nanoparticles and its applications in bioimaging and in vitro anti-tumor effect

In this contribution, a novel AIE monomers 2-(4-styrylphenyl)-1,2-diphenylvinyl)styryl)pyridine (SDVPY) with smart fluorescent pH-sensitivity basing on tetraphenylethylene-pyridine were successfully synthesized for the first time, subsequently, a series of amphiphilic copolymers PEG-PY were achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of SDVPY and poly(ethylene glycol) methacrylate (PEGMA), which would self-assemble in water solution to form core-shell nanoparticles (PEG-PY FONs) with about 150nm diameter. The PEG-PY FONs showed obvious fluorescence response to Fe3+, HCO3- and CO32- ions in aqueous solution owing to their smart pH-sensitivity and AIE characteristics, and their maximum emission wavelength could reversibly change from 525nm to 624nm. The as-prepared PEG-PY FONs showed also prospective application in cells imaging with the variable fluorescence for different pH cells micro-environment. When PEG-PY copolymers self-assembled with the anti-tumor drug paclitaxel (PTX), the obtained PY-PTX FONs could effectively deliver and release PTX with pH-sensitivity, and could be easily internalized by A549 cells and located at the cytoplasm with high cytotoxicity, which was further confirmed by the Calcein-AM/PI staining of dead and alive A549 cells. Moreover, the flow cytometry results indicated that the PY-PTX FONs could obviously induce the apoptosis of A549 cells, which further showed the great potential of PY-PTX FONs in the application of tumors therapy.

Two red/blue-emitting fluorescent probes for quick, portable, and selective detection of thiophenol in food, soil and plant samples, and their applications in bioimaging

Thiophenol (PhSH), which is widely used in many industries, poses significant health risks owing to its acute toxicity and irritating effects. Thus, the detection of PhSH is crucial for ensuring environmental and food safety. There is significant room for improvement in the sensing properties of the reported analytical methods, such as response time, detection limit, selectivity, and portable detection. Herein, we present two new red/blue fluorescence-emissive sensors (NS1 and NS2) for PhSH detection. After reacting with PhSH, NS1 exhibited a low detection limit (66.7 nM), red emission, fast response time of just 10 s, and large Stokes shift (240 nm). NS2 could detect PhSH with a low detection limit (75.8 nM), fast response time of 20 s, and blue emission. The noticeable color response and portability of the two probes made them suitable for on-site detection of PhSH in various samples, such as water, soil, plant, food samples, and living cells. Moreover, it has been shown that these probes could be used to determine PhSH content in smartphone applications, thin layer chromatography kits, and polysulfone capsule kits. Prepared probes have low cytotoxicity and show good permeability in tested living cells, which is important for early diagnosis, disease research, and emergency analysis. Compared with other studies, the proposed approach has remarkable advantages in terms of detection limit, portability, response time, and low cytotoxicity. Thus, it meets the crucial demand for ensuring health, environmental and food safety, and adherence to regulatory standards.

Functionalized Nanomaterials Capable of Crossing the Blood-Brain Barrier.

The blood-brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.

Melanin-Inspired Composite Materials: From Nanoarchitectonics to Applications.

Synthetic melanin is a mimic of natural melanin analogue with intriguing properties such as metal-ion chelation, redox activity, adhesion, and broadband absorption. Melanin-inspired composite materials are formulated by assembly of melanin with other types of inorganic and organic components to target, combine, and build up the functionality, far beyond their natural capabilities. Developing efficient and universal methodologies to prepare melanin-based composite materials with unique functionality is vital for their further applications. In this review, we summarize three types of synthetic approaches, predoping, surface engineering, and physical blending, to access various melanin-inspired composite materials with distinctive structure and properties. The applications of melanin-inspired composite materials in free radical scavenging, bioimaging, antifouling, and catalytic applications are also reviewed. This review also concludes current challenges that must be addressed and research opportunities in future studies.

Photoluminescence lifetime engineering via organic resonant films with molecular aggregates

Abstract Manipulating the spontaneous emission rate of fluorophores is vital in creating bright incoherent illumination for optical sensing and imaging, as well as fast single-photon sources for quantum technology applications. This can be done via increasing the Purcell effect by using non-monolithic optical nanocavities; however, achieving the desired performance is challenging due to difficulties in fabrication, precise positioning, and frequency tuning of cavity-emitter coupling. Here, we demonstrate a simple approach to achieve a wavelength-dependent photoluminescence (PL) lifetime modification using monolithic organic molecular aggregates films. These single monolithic organic films are designed to have a Lorentzian dispersion, including epsilon-near-zero (ENZ) and epsilon-near-pole (ENP) spectral regions with increased and decreased photonic density of states, respectively. This dispersion leads to enhanced and depressed PL decay rates at different wavelengths. Both time-resolved photoluminescence (TRPL) and fluorescence lifetime imaging microscopy (FLIM) measurements are implemented to verify the validity of this approach. This approach offers a promising way to design dual-functional optical sources for a variety of applications, including bioimaging, sensing, data communications, and quantum photonics applications.

Fluorescence-based ratiometric sensors as emerging tools for CN− detection: Chemical structures, sensing mechanisms and applications

Hazardous cyanide anions (CN−) are increasingly threatening the environment and human health due to their widespread use in industry and many other fields. Over the past three decades, a large number of probes have been reported to sensitively and selectively detect this toxic anion, while a rather limited number of ratiometric fluorescent probes have been developed. The ratiometric probes have significant potential in bio-imaging and biomedical applications because of the ability to detect CN− in a quick, convenient and affordable way. In this review, we introduce 42 ratiometric fluorescent probes reported in the past 6 years (2018–2023) for CN– detection. Our description includes the chemical structures, photo-physical properties, CN− sensing mechanisms, solution color changes, limits of detection (LODs) and/or various applications of these chemical probes. This review provides guidelines for design and development of a new ratiometric probe for effective CN− detection.

Effectively enhancing red fluorescence strategy and bioimaging applications of carbon dots

Red-emitting carbon dots have attracted much attention because of their excellent fluorescence properties. It is of great significance to synthesize red-emitting carbon dots with high fluorescence quantum yield. Herein, by using citric acid and 1,8-diaminonaphthalene as precursors in N, N-dimethylformamide, novel carbon dots (NC-CDs) exhibiting red emission at 607 nm upon excitation at 514 nm were synthesized via a solvent-thermal approach. NC-CDs aggregated in lipid droplets of cells, and hemin quenched their fluorescence. Subsequently, cationic surfactants cetyltrimethylammonium bromide, anionic surfactants sodium dodecyl sulfate and nonionic surfactants were used to functionalize the NC-CDs. The results indicated that both ionic surfactants increased the fluorescence quantum yield and solubility of NC-CDs with extended fluorescence lifetime. This approach is applicable to a class of carbon dots that possess both carboxyl and amino groups. Additionally, these functionalized NC-CDs exhibited high recognition sensitivity towards ClO− and Cu2+ respectively except for hemin. This study provides a novel approach for the synthesis of highly red-emitting carbon dots, expanding their applications in the field of biological imaging and sensing. The findings hold significant implications for the real-time monitoring of hemin in lipid droplets. Additionally, this work offers a simple method to dramatic enhance their fluorescence quantum yield.

Biogenic zinc selenide nanoparticles fabricated using Rosmarinus officinalis leaf extract with potential biological activity

Zinc selenide nanoparticles (ZnSe) are semiconductor metals of zinc and selenium. ZnSe NPs are advantageous for biomedical and bio-imaging applications due to their low toxicity. ZnSe NPs can be used as a therapeutic agent by synthesizing those using biologically safe methods. As a novel facet of these NPs, plant-based ZnSe NPs were fabricated from an aqueous extract of Rosmarinus officinalis L. (RO extract). Physiochemical analyses such as UV-visible and FTIR spectroscopy, SEM-EDX and TEM Imaging, XRD and DLS-Zeta potential analyses confirmed the biological fabrication of RO-ZnSe NPs. Additionally, Ro-ZnSe NPs were investigated for their bioactivity. There was an apparent peak in the UV-visible spectrum at 398 nm to confirm the presence of ZnSe NPs. FTIR analysis confirmed RO-extract participation in ZnSe NPs synthesis by identifying putative functional groups associated with biomolecules. TEM and SEM analyses revealed that RO-ZnSe NPs have spherical shapes in the range of 90–100 nm. According to XRD and EDX analysis, RO-ZnSe NPs had a crystallite size of 42.13 nm and contain Se and Zn (1:2 ratio). These NPs demonstrated approximately 90.6% antioxidant and antibacterial activity against a range of bacterial strains at 100 µg/ml. Antibiofilm activity was greatest against Candida glabrata and Pseudomonas aeruginosa at 100 g/ml. Accordingly, the IC50 values for anticancer activity against HTB-9, SW742, and HF cell lines were 14.16, 8.03, and 35.35 g/ml, respectively. In light of the multiple applications for ZnSe NPs, our research indicates they may be an excellent option for biological and therapeutic purposes in treating cancers and infections. Therefore, additional research is required to determine their efficacy.

An innovative near-infrared fluorescent probe with FRET effect for the continuous detection of Zn2+ and PPi with high sensitivity and selectivity, and its application in bioimaging

As the second most abundant transition metal element in the human body, zinc ions play an important role in the normal growth and development of the human body. We have successfully synthesized a near-infrared fluorescent probe with FRET effect for the detection of Zn2+. Probe DR6G has good selectivity and anti-interference ability for Zn2+. When Zn2+ is added to the probe DR6G solution, it responds completely within seconds, releasing red fluorescence with a detection limit of 2.02 × 10−8 M. As the main product of ATP hydrolysis, PPi is indispensable in various metabolic activities in cells and the human body. Due to the strong binding ability of Zn2+ and PPi, it is easy to form ZnPPi precipitation, so we added PPi to the solution to complete the Zn2+ detection, and realized the continuous detection of PPi, and the detection limit was 2.06 × 10−8 M. Since Zn2+ and PPi play an important role in vivo, it is of great practical significance to design and synthesize a fluorescent probe that can continuously detect Zn2+ and PPi. Biological experiments have shown that the probe DR6G has low cytotoxicity and can complete the detection of exogenous Zn2+ and PPi in cells and living mice in vitro. Bacterial experiments have shown that the DR6G probe also has certain research value in the field of environmental monitoring and microbiology. Due to the constant variation of the fluorescence signals of Zn2+ and PPi during detection, we designed the logic gate program. In practical applications, the probe DR6G can quantitatively detect Zn2+ in zinc-containing oral liquids and qualitatively detect PPi in toothpaste.