Stretchable ionic-electronic bilayer hydrogel electronics enable in situ detection of solid-state epidermal biomarkers.

Continuous and in situ detection of biomarkers in biofluids (for example, sweat) can provide critical health data but is limited by biofluid accessibility. Here we report a sensor design that enables in situ detection of solid-state biomarkers ubiquitously present on human skin. We deploy an ionic-electronic bilayer hydrogel to facilitate the sequential dissolution, diffusion and electrochemical reaction of solid-state analytes. We demonstrate continuous monitoring of water-soluble analytes (for example, solid lactate) and water-insoluble analytes (for example, solid cholesterol) with ultralow detection limits of 0.51 and 0.26 nmol cm-2, respectively. Additionally, the bilayer hydrogel electrochemical interface reduces motion artefacts by a factor of three compared with conventional liquid-sensing electrochemical interfaces. In a clinical study, solid-state epidermal biomarkers measured by our stretchable wearable sensors showed a high correlation with biomarkers in human blood and dynamically correlated with physiological activities. These results present routes to universal platforms for biomarker monitoring without the need for biofluid acquisition.

Development of Blood-Cell-Selective Fluorescent Biodots for Lysis-Free Leukocyte Imaging and Differential Counting in Whole Blood.

Complete blood count with leukocyte (white blood cell, WBC) differential is one of the most frequently ordered clinical test for disease diagnosis. Herein, multifunctional fluorescent carbon dots derived from biomolecules (biodots) for rapid lysis-free whole blood analysis are developed. Specifically, two types of biodots are molecularly engineered through hydrothermal synthesis for differential blood cells labeling. Type I biodots synthesized from amino acid (serine/threonine) precursors and passivated with polyethylenimine can label both red blood cells (RBCs) and WBCs with excellent contrast in fluorescence intensity, enabling direct counting of leukocytes in whole blood samples without a tedious RBC lysis step. It also allows three-part leukocyte differential counting by flow cytometry without using expensive fluorophore-conjugated antibodies. On the other hand, Type II biodots synthesized from the same amino acid precursors but passivated with a biopolymer (chitosan) are able to selectively lyse RBCs with greater than 98% efficiency to allow simultaneous fluorescent labeling of leukocytes for WBC counting in whole blood. It is envisioned that these novel nanoreagents, which eliminate the cumbersome lysis and antibody conjugation steps for selective labeling of different blood cells, would revolutionize disease diagnostics toward achieving faster, cheaper, and more accurate whole blood analyses in one test.

Noncovalent Fluorescent Biodot-Protein Conjugates with Well-Preserved Native Functions for Improved Sweat Glucose Detection.

To overcome the traditional issues of protein labeling, we report herein an effective approach for noncovalent conjugation of the biomolecule-derived fluorescent nanodots (biodot) to functional proteins without the addition of chemical linkers for biosensor development. The as-prepared fluorescent biodot-protein conjugates are very stable near physiological pH, exhibiting excellent photostability and thermal stability. More importantly, the native functions of proteins, including drug binding and enzymatic activities, are well-preserved after conjugating with biodots. The optimized protein conjugation strategy is then applied to prepare biodot-glucose oxidase (GOx) fluorescent sensing probes for sweat glucose detection. Results show that the as-prepared sensing probes could achieve better assay performance than those covalent conjugates as demonstrated herein. Specifically, GOx in the noncovalently bound conjugates are able to catalyze the oxidation of glucose effectively, which generates hydrogen peroxide as a byproduct. In the presence of Fe2+, Fenton reaction takes place to produce hydroxyl radicals and Fe3+, leading to significant fluorescence quenching of biodots on the conjugates. This simple one-step enzymatic assay in a single probe achieves a wide linear range of 25-1000 µM (R2 = 0.99) with a low detection limit of 25 µM. Furthermore, negligible interference is observed in the complex artificial sweat sample for accurate glucose quantification, achieving an excellent recovery rate of 100.5 ± 2.2%. This work provides a facile conjugation method that is generally applicable to a wide range of proteins, which will help to accelerate future development of multifunctional fluorescent probes to provide optical signals with unique protein functions (e.g., enzymatic, recognition, etc.) for biomedical sensing and imaging.

[Efficacy Observation of Modified Yiqi Chutan Recipe Treating Mid-late Stage NSCLC Patients by CT Perfusion].

OBJECTIVE: To observe the effect of Modified Yiqi Chutan Recipe (MYCR) on blood flow perfusion in treating mid-late stage non-small cell lung cancer (NSCLC) patients by using multislice CT perfusion (CTP) , and to assess the relationship between each CTP parameter and the prognosis as well. METHODS: Totally 87 mid-late stage NSCLC patients were randomly assigned to the treatment group (44 cases, Shenyi Capsule + MYCR +chemotherapy) and the control group (43 cases, chemotherapy alone) in the ratio of 1:1. And 21 days consisted of 1 therapeutic course, 4 courses in total. All of them underwent CTP of primary tumor and routine thoracic CT examination (plain CT and enhancement CT) 3 times (before therapy, after 2 and 4 cycles). CT findings were analyzed for tumor size and perfusion parameters [blood flow (BF), blood volume (BV), permeability surface (PS), mean transit time (MTT), and time to peak (TP) before and after treatment, and relationship between perfusion parameters and prognosis was also assessed. RESULTS: In 87 cases, 7 dropped out and 80 cases were available, 40 in the treatment group and 40 in the control group. (1) The relief rate was 47.5% (19/40) and the total stable rate was 77.5% (31/40) in the treatment group, and they were 40.0% (16/40) and 65.0% (26/40) in the control group, with no statistical difference between the two groups (χ² = 0.672, 1.227; P > 0.05). (2) Compared with before treatment group in the same group, BF and PS decreased, and MTT increased in the two groups after 2 and 4 courses (P < 0.05); BE and PS decreased, and MTT increased in the control group after 2 courses (P < 0.05). Compared with the control group after 4 courses, BE decreased more significantly in the treatment group (P < 0.05). (3) After 4 courses, all patients were assigned to the remission group (35 cases) and the non-remission group (45 cases) according to the RECIST standard. Compared with before treatment in the same group, BF, BF, and PS all decreased, and MTT increased in the remission group after treatment (all P < 0.05); BF increased in the non-remission group after treatment (P < 0.05). (4) All patients were assigned to the BE increase group (34 cases) and the BE decrease group (46 cases) according to changed BE values after treatment. Results showed the mean survival rate was 246 days in the BF increase group (the 1-year accumulative survival rate being 13.0%) and 387 days in the BE decrease group (the 1-year accumulative survival rate being 53.1%). The life span was prolonged and the 1-year accumulative survival rate was elevated in the BE increase group, with statistical difference as compared with the BE decrease group (χ² = 19.057, P < 0.01). CONCLUSIONS: Shenyi Capsule plus MYCR could reduce BE in mid-late stage NSCLC patients , improve vascular permeability, showing better synergistic effect with chemotherapy. CTP could not only reflect the change of tumor size, but also reflect vascular function of the tumor. Meanwhile, changes of CTP parameters were closely associated with prognosis. Patients with post-treatment decreased BE value had better prognosis and longer life span.

Glowing graphene quantum dots and carbon dots: properties, syntheses, and biological applications.

The emerging graphene quantum dots (GQDs) and carbon dots (C-dots) have gained tremendous attention for their enormous potentials for biomedical applications, owing to their unique and tunable photoluminescence properties, exceptional physicochemical properties, high photostability, biocompatibility, and small size. This article aims to update the latest results in this rapidly evolving field and to provide critical insights to inspire more exciting developments. We comparatively review the properties and synthesis methods of these carbon nanodots and place emphasis on their biological (both fundamental and theranostic) applications.

Reference intervals for thyroid function from the fifth to seventh day of life in twin-pregnancy preterm neonates: an 8-year retrospective study.

PURPOSE: The immature and developing hypothalamic-pituitary-thyroid axis leads to different levels of thyroid function in twin neonates, including free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) levels. No reference intervals for twins have been established until now. To compensate for this lack, we collected data and established this standard across different gestational ages (GAs) and sexes. METHODS: A total of 273 pairs of neonates admitted to the NICU in Southeast China from 2015 to 2022 were included. Each pair was divided into Neonate A (relatively heavy birth weight (BW)) and Neonate B (relatively light BW). Their thyroid functions were analyzed to establish reference intervals and comparisons were made stratified by GA and sex. RESULTS: The FT3, FT4, and TSH reference intervals in twin neonates with a GA of 26-36 weeks were as follows: Neonate A and B: 3.59 ± 0.99 and 3.57 ± 1.00 pmol/L; Neonate A and B: 17.03 ± 5.16 and 16.77 ± 5.29 pmol/L; and Neonate A and B: 4.097 ± 3.688 and 4.674 ± 4.850 mlU/L, respectively. There were significant differences between serum FT3 and FT4 reference intervals and GA (p < 0.05). The serum FT3 and FT4 reference intervals for male neonates were lower than those for female neonates in the 29-32-week group (p < 0.05). CONCLUSION: This was the first study, to our knowledge, to establish reference intervals for thyroid function in twin neonates from the fifth to seventh day of life, which will be beneficial for the diagnosis and management of congenital hypothyroidism.

Skin-Attachable Ink-Dispenser-Printed Paper Fluidic Sensor Patch for Colorimetric Sweat Analysis.

In situ analysis of sweat biomarkers potentially provides noninvasive lifestyle monitoring and early diagnosis. Quantitative detection of sweat rate is crucial for thermoregulation and preventing heat injuries. Here, a skin-attachable paper fluidic patch is reported for in situ colorimetric sensing of multiple sweat markers (pH, glucose, lactate, and uric acid) with concurrent sweat rate tracking. Two sets of fluidic patterns-multiplexed detection zones and a longitudinal sweat rate channel-are directly printed by an automated ink dispenser from a specially developed ceramic-based ink. The ceramic ink thermal-cures into an impervious barrier, confining sweat within the channels. The ceramic-ink-printed boundary achieves higher pattern resolution, prevents fluid leakage, attains pattern thermal stability, and resistant to organic solvents. The cellulose matrix of the detection zones is modified with nanoparticles to improve the color homogeneity and sweat sensor sensitivity. The sweat rate channel is made moisture sensitive by incorporating a metal-salt-based dye. The change in saturation/color of the detection zones and/or channels upon sweat addition can be visually detected or quantified by a smartphone camera. A cost-effective way is provided to fabricate paper fluidic sensor patches, successfully demonstrating on-body multiplexed evaluation of sweat analytes. Such skin wearables offer on-site analysis, meaningful to an increasingly health-conscious population.

Single cell analysis at the nanoscale.

The fundamental life processes such as signal transduction, intracellular trafficking, protein degradation, and DNA repair often occur in nanometric subcellular compartments. It is essential to conduct single cell analysis specifically at the nanoscale to fully understand the critical cellular processes while providing important medical applications. However, there are great challenges in achieving high spatial resolution in single cells for uncovering spatial heterogeneity, high sensitivity for biomolecule detections and high specificity in complicated cellular environment. In this tutorial review, we survey recent progress toward single cell analysis at the nanoscale by emphasizing how the advancement in nanotechnology has brought a plethora of nanotools to interrogate single cells with high spatiotemporal resolutions. In particular, analysis principle, nanoscale probe fabrication, high resolution cellular analysis, data collection and processing are introduced. New cell biochemistry and biology insights revealed by the unique single cell analysis methods are highlighted. The perspectives on future opportunities and unsolved challenges are also discussed.

Antibody conjugated Au/Ir@Cu/Zn-MOF probe for bacterial lateral flow immunoassay and precise synergistic antibacterial treatment.

Staphylococcus aureus is one of the most prevalent threats to public health. Rapid detection with high sensitivity and targeted killing is crucial to curb its spread. Herein, a metal-bearing nanocomposite, consisting of a bimetallic nanoparticle and a metal-organic framework (Au/Ir@Cu/Zn-MOF) was constructed. Upon conjugation with anti-S. aureus antibody, this nanocomposite (Ab-Au/Ir@Cu/Zn-MOF) was exploited for its dual functions, i.e. as a reporting probe in a lateral flow immunoassay and a high efficiency antibacterial reagent. Benefiting from the enrichment of Au/Ir NPs by the Cu/Zn-MOF, the Au/Ir@Cu/Zn-MOF-based lateral flow immunoassay sensor exhibited a visual limit of detection of 103 CFU/mL, which was100 times more sensitive than Au/Ir-based sensor. Moreover, the Ab-Au/Ir@Cu/Zn-MOF probe possessed synergistic photothermal-chemodynamic bactericidal effect that specifically targeted against S. aureus. Under a co-treatment by H2O2 (0.4 mM) and 808 nm near infrared irradiation (1 W/cm2, 5 min), complete sterilization of 5 × 105-106 CFU/mL S. aureus was achieved at a nanocomposite concentration as low as 6.25 µg/mL. The superior antibacterial efficiency was attributable to the three-fold properties of the Ab-Au/Ir@Cu/Zn-MOF probe: (1) enhanced multi-enzyme mimicking activities that promote reactive oxygen species generation, (2) high photothermal activity (efficiency of 53.70%), and (3) bacteria targeting ability via the antibody coating. By changing the antibody, this nanocomposite can be tailored to target a wide range of bacteria species, for detection and for precise antibacterial treatment.

Carbon Dot-Doped Hydrogel Sensor Array for Multiplexed Colorimetric Detection of Wound Healing.

Effective wound care and treatment require a quick and comprehensive assessment of healing status. Here, we develop a carbon dot-doped hydrogel sensor array in polydimethylsiloxane (PDMS) for simultaneous colorimetric detections of five wound biomarkers and/or wound condition indicators (pH, glucose, urea, uric acid, and total protein), leading to the holistic assessment of inflammation and infection. A biogenic carbon dot synthesized using an amino acid and a polymer precursor is doped in an agarose hydrogel matrix for constructing enzymatic sensors (glucose, urea, and uric acid) and dye-based sensors (pH and total protein). The encapsulated enzymes in such a matrix exhibit improved enzyme kinetics and stability compared to those in pure hydrogels. Such a matrix also provides stable colorimetric responses for all five sensors. The sensor array exhibits high accuracy (recovery rates of 91.5-113.1%) and clinically relevant detection ranges for all five wound markers. The sensor array is established for simulated wound fluids and validated with rat wound fluids from perturbed wound models. Distinct color patterns are obtained that can clearly distinguish healing vs nonhealing wounds visually and quantitatively. This hydrogel sensor array shows great potential for on-site wound sensing due to its long-term stability, lightweight, and flexibility.

Battery-free and AI-enabled multiplexed sensor patches for wound monitoring.

Wound healing is a dynamic process with multiple phases. Rapid profiling and quantitative characterization of inflammation and infection remain challenging. We report a paper-like battery-free in situ AI-enabled multiplexed (PETAL) sensor for holistic wound assessment by leveraging deep learning algorithms. This sensor consists of a wax-printed paper panel with five colorimetric sensors for temperature, pH, trimethylamine, uric acid, and moisture. Sensor images captured by a mobile phone were analyzed by neural network-based machine learning algorithms to determine healing status. For ex situ detection via exudates collected from rat perturbed wounds and burn wounds, the PETAL sensor can classify healing versus nonhealing status with an accuracy as high as 97%. With the sensor patches attached on rat burn wound models, in situ monitoring of wound progression or severity is demonstrated. This PETAL sensor allows early warning of adverse events, which could trigger immediate clinical intervention to facilitate wound care management.

Anticancer efficacy and subcellular site of action investigated by real-time monitoring of cellular responses to localized drug delivery in single cells.

Subcellular-targeted drug delivery has much potential to defeat infectious diseases and cancers. Medical and/or biochemical effects of drugs/bioactive molecules delivered to subcellular compartments and their subcellular sites of action need to be investigated but have not been explored. Here the subcellular location-dependent biochemical responses of a potent anticancer drug, ß-lapachone (ß-lap), is investigated by a reduced graphene oxide (rGO)-functionalized optical nanoprobe, which can deliver and simultaneously monitor the drug effects at nanoscales. For the first time, distinct oxidative responses and calcium alterations in three selected subcellular domains are observed and clearly pinpoint that the perinuclear region is the optimal subcellular site for ß-lap to have the best anticancer efficacy. The results presented here provide not only scientific insights of subcellular drug-cell interaction that is not obtainable from conventional methods, but they also provide valuable knowledge for rational design of subcellular-targeted delivery or spatially resolved signal intervention.

Restoring basal planes of graphene oxides for highly efficient loading and delivery of ß-lapachone.

An efficient and biocompatible drug nanocarrier is essential for nanomedicines to realize their full therapeutic potential. Here, we investigate the loading of a selective and potent anticancer drug, ß-lapachone (ß-lap), on a magnetite nanoparticle-decorated reduced graphene oxide (Fe(3)O(4)/rGO) and the in vitro anticancer efficacy of ß-lap loaded Fe(3)O(4)/rGO. Reduced graphene oxide (rGO) with magnetic functionality was prepared via electrostatic interaction between positively charged magnetite (Fe(3)O(4)) nanoparticles and negatively charged GO, followed by hydrazine reduction of GO to rGO. The prepared Fe(3)O(4)/rGO shows that Fe(3)O(4) makes the Fe(3)O(4)/rGO hybrid magnetically separable for easy handling during drug loading and release and the Fe(3)O(4)/rGO hybrid exhibits significantly higher loading capacity than that of Fe(3)O(4)/GO, suggesting that restoration of the graphene basal plane upon reduction of GO enhances the interaction between ß-lap and rGO. Cellular uptake studies using fluorescently labeled Fe(3)O(4)/rGO verifies successful internalization of Fe(3)O(4)/rGO into the cytoplasm while rGO without hybridized Fe(3)O(4) has poor uptake performance. Furthermore, ß-lap loaded Fe(3)O(4)/rGO shows remarkably high cytotoxicity toward MCF-7 breast cancer cells while the blank Fe(3)O(4)/rGO produces no cytotoxic effects. The cytotoxicity results suggest that Fe(3)O(4)/rGO is an efficient drug carrier for anticancer treatments. The fine-tuning of the chemical structures of graphene oxides by reduction chemistry may provide a universal route for controlled loading and release of drugs or biomolecules to construct advanced delivery vehicles.

Stimuli-Activable Metal-Bearing Nanomaterials and Precise On-Demand Antibacterial Strategies.

Bacterial infections remain the leading cause of death worldwide today. The emergence of antibiotic resistance has urged the development of alternative antibacterial technologies to complement or replace traditional antibiotic treatments. In this regard, metal nanomaterials have attracted great attention for their controllable antibacterial functions that are less prone to resistance. This review discusses a particular family of stimuli-activable metal-bearing nanomaterials (denoted as SAMNs) and the associated on-demand antibacterial strategies. The various SAMN-enabled antibacterial strategies stem from basic light and magnet activation, with the addition of bacterial microenvironment responsiveness and/or bacteria-targeting selectivity and therefore offer higher spatiotemporal controllability. The discussion focuses on nanomaterial design principles, antibacterial mechanisms, and antibacterial performance, as well as emerging applications that desire on-demand and selective activation (i.e., medical antibacterial treatments, surface anti-biofilm, water disinfection, and wearable antibacterial materials). The review concludes with the authors' perspectives on the challenges and future directions for developing industrial translatable next-generation antibacterial strategies.

Colorimetric microneedle patches for multiplexed transdermal detection of metabolites.

Skin Interstitial Fluid (ISF) is an alternative source for biomarkers. Herein, a highly swellable microneedle patch (MNP) to rapidly extract ISF painlessly and bloodlessly is presented. The MNP is made of crosslinked methacrylated hyaluronic acid (MeHA) and dissolvable hyaluronic acid (HA) with the optimal balance of mechanical strength (0.6 N/MN) and absorption capability (16.22 µL in 20 min). Incorporated with wax-patterned and sensing-reagent-decorated test paper (TP) for multiplexed colorimetric detection of metabolites (glucose, lactate, cholesterol, and pH), this TP-MNP biosensor gives rapid color change in biomarker concentration-dependent manner based on specific enzymatic reactions, whereby allowing diagnosis by the naked eye or quantitative RGB analysis. Both the in vitro and in vivo experiments demonstrate the feasibility of TP-MNPs to detect multiple biomarkers in skin interstitial fluid within minutes. Such convenient and self-administrable profiling of metabolites shall be instrumental for home-based long-term monitoring and management of metabolic diseases.

Optical detection of single cell lactate release for cancer metabolic analysis.

Sensitive detection of extracellular lactate concentrations at a single cell level is of importance for studying the metabolic alterations in tumor progression. A unique nanoscale optical fiber lactate sensor was developed to monitor the extracellular lactate concentrations of cancer cells by immobilizing its nanotip with lactate dehydrogenases, which could catalyze lactate conversion to generate NADH for sensitive fluorescence detection. The results demonstrate that the fabricated nanosensor can successfully detect the extracellular lactate concentrations for single HeLa, MCF-7, and human fetal osteoblast (hFOB) cells, showing that the cancer cells have distinctly higher extracellular lactate concentrations than normal cells as that predicted by Warburg effect. The nanosensor was also employed to investigate the effect of a monocarboxylate transporter inhibitor on the lactate efflux from cancer cells. Different lactate efflux inhibition profiles were obtained for HeLa and MCF-7 cell lines. This work demonstrates that the nanosensor has potential for evaluating the effect of metabolic agents on cancer metabolism and survival.

Recent development of nucleic acid nanosensors to detect sequence-specific binding interactions: From metal ions, small molecules to proteins and pathogens.

DNA carries important genetic instructions and plays vital roles in regulating biological activities in living cells. Proteins such as transcription factors binds to DNA to regulate the biological functions of DNA, and similarly many drug molecules also bind to DNA to modulate its functions. Due to the importance of protein-DNA and drug-DNA binding, there has been intense effort in developing novel nanosensors in the same length scale as DNA, to effectively study these binding interactions in details. In addition, aptamers can be artificially selected to detect metal ions and pathogens such as bacteria and viruses, making nucleic acid nanosensors more versatile in detecting a large variety of analytes. In this minireview, we first explained the different types and binding modes of protein-DNA and drug-DNA interactions in the biological systems, as well as aptamer-target binding. This was followed by the review of five types of nucleic acid nanosensors based on optical or electrochemical detection. The five types of nucleic acid nanosensors utilizing colorimetric, dynamic light scattering (DLS), surface-enhanced Raman spectroscopy (SERS), fluorescence and electrochemical detections have been recently developed to tackle some of the challenges in high-throughput screening technology for large scale analysis, which is especially useful for drug development and mass screening for pandemic outbreak such as SARS or COVID-19.

Colorimetric biosensors for point-of-care virus detections.

Colorimetric biosensors can be used to detect a particular analyte through color changes easily by naked eyes or simple portable optical detectors for quantitative measurement. Thus, it is highly attractive for point-of-care detections of harmful viruses to prevent potential pandemic outbreak, as antiviral medication must be administered in a timely fashion. This review paper summaries existing and emerging techniques that can be employed to detect viruses through colorimetric assay design with detailed discussion of their sensing principles, performances as well as pros and cons, with an aim to provide guideline on the selection of suitable colorimetric biosensors for detecting different species of viruses. Among the colorimetric methods for virus detections, loop-mediated isothermal amplification (LAMP) method is more favourable for its faster detection, high efficiency, cheaper cost, and more reliable with high reproducible assay results. Nanoparticle-based colorimetric biosensors, on the other hand, are most suitable to be fabricated into lateral flow or lab-on-a-chip devices, and can be coupled with LAMP or portable PCR systems for highly sensitive on-site detection of viruses, which is very critical for early diagnosis of virus infections and to prevent outbreak in a swift and controlled manner.

Nucleotide-derived theranostic nanodots with intrinsic fluorescence and singlet oxygen generation for bioimaging and photodynamic therapy.

Nucleic acids are important molecules of life and have recently emerged as important functional materials to synthesize, organize and assemble inorganic nanoparticles for various technological applications. In this study, we have systematically investigated the four basic nucleotides of DNA as precursors to form fluorescent nucleotide derived biodots (N-dots) with unique singlet oxygen generation properties by one-pot hydrothermal synthesis. It has been discovered for the first time that the nitrogenous base adenine accounts for the bright fluorescence, while the sugar and phosphate groups of the nucleotide endow the N-dots with good photo-stability. Among the N-dots synthesized in this study, adenosine triphosphate (ATP)-dots were found to exhibit the highest fluorescence quantum yield (QY) of 13.9%, whereas adenosine diphosphate (ADP)-dots exhibited the best photo-stability maintaining 97.6% photoluminescence intensity after continuous UV excitation for 30 min. Overall, deoxyadenosine monophosphate (dAMP)-dots display both high fluorescence QY (12.4%) and good photo-stability (91.9%). Most critically, dAMP-dots show the highest singlet oxygen generation with a remarkable singlet oxygen (1O2) quantum yield of 1.20 surpassing the 1O2 quantum yield of the conventional photosensitizer Rose Bengal (0.75). Further cellular experiments reveal that dAMP-dots possess excellent cellular uptake ability for successful fluorescent labeling with the ability to kill >60% HeLa cancer cells under white light treatment within 10 minutes. Additionally, N-dots possess excellent stability against both UV irradiation and DNase enzymatic action. These results demonstrate the unique physiochemical properties of N-dots, including an ultra-small size for cellular uptake, tunable photoluminescence for bioimaging, excellent aqueous solubility, high chemical stability and photo-stability as well as excellent singlet oxygen quantum yield with inherent biocompatibility for photodynamic therapy, which are important factors contributing to the promising theranostic applications in future personalized nanomedicine.

Uncovering the Design Principle of Amino Acid-Derived Photoluminescent Biodots with Tailor-Made Structure-Properties and Applications for Cellular Bioimaging.

Natural amino acids possess side chains with different functional groups (R groups), which make them excellent precursors for programmable synthesis of biomolecule-derived nanodots (biodots) with desired properties. Herein, we report the first systematic study to uncover the material design rules of biodot synthesis from 20 natural α-amino acids via a green hydrothermal approach. The as-synthesized amino acid biodots (AA dots) are comprehensively characterized to establish a structure-property relationship between the amino acid precursors and the corresponding photoluminescent properties of AA dots. It was found that the amino acids with reactive R groups, including amine, hydroxyl, and carboxyl functional groups form unique C-O-C/C-OH and N-H bonds in the AA dots which stabilize the surface defects, giving rise to brightly luminescent AA dots. Furthermore, the AA dots were found to be amorphous and the length of the R group was observed to affect the final morphology (e.g., disclike nanostructure, nanowire, or nanomesh) of the AA dots, which in turn influence their photoluminescent properties. It is noteworthy to highlight that the hydroxyl-containing amino acids, that is, Ser and Thr, form the brightest AA dots with a quantum yield of 30.44% and 23.07%, respectively, and possess high photostability with negligible photobleaching upon continuous UV exposure for 3 h. Intriguingly, by selective mixing of Ser or Thr with another amino acid precursor, the resulting mixed AA dots could inherit unique properties such as improved photostability and significant red shift in their emission wavelength, producing enhanced green and red fluorescent intensity. Moreover, our cellular studies demonstrate that the as-synthesized AA dots display outstanding biocompatibility and excellent intracellular uptake, which are highly desirable for imaging applications. We envision that the material design rules discovered in this study will be broadly applicable for the rational selection of amino acid precursors in the tailored synthesis of biodots.