Engineered polymer nanoparticles as artificial chaperones facilitating the selective refolding of denatured enzymes.

Molecular chaperones assist in protein refolding by selectively binding to proteins in their nonnative states. Despite progress in creating artificial chaperones, these designs often have a limited range of substrates they can work with. In this paper, we present molecularly imprinted flexible polymer nanoparticles (nanoMIPs) designed as customizable biomimetic chaperones. We used model proteins such as cytochrome c, laccase, and lipase to screen polymeric monomers and identify the most effective formulations, offering tunable charge and hydrophobic properties. Utilizing a dispersed phase imprinting approach, we employed magnetic beads modified with destabilized whole-protein as solid-phase templates. This process involves medium exchange facilitated by magnetic pulldowns, resulting in the synthesis of nanoMIPs featuring imprinted sites that effectively mimic chaperone cavities. These nanoMIPs were able to selectively refold denatured enzymes, achieving up to 86.7% recovery of their activity, significantly outperforming control samples. Mechanistic studies confirmed that nanoMIPs preferentially bind denatured rather than native enzymes, mimicking natural chaperone interactions. Multifaceted analyses support the functionality of nanoMIPs, which emulate the protective roles of chaperones by selectively engaging with denatured proteins to inhibit aggregation and facilitate refolding. This approach shows promise for widespread use in protein recovery within biocatalysis and biomedicine.

Therapeutic Peptides Are Preferentially Solubilized in Specific Microenvironments within PEG-PLGA Polymer Nanoparticles.

Polymeric nanoparticles are a highly promising drug delivery formulation. However, a lack of understanding of the molecular mechanisms that underlie their drug solubilization and controlled release capabilities has hindered the efficient clinical translation of such technologies. Polyethylene glycol-poly(lactic-co-glycolic) acid (PEG-PLGA) nanoparticles have been widely studied as cancer drug delivery vehicles. In this letter, we use unbiased coarse-grained molecular dynamics simulations to model the self-assembly of a PEG-PLGA nanoparticle and its solubulization of the anticancer peptide, EEK, with good agreement with previously reported experimental structural data. We applied unsupervised machine learning techniques to quantify the conformations that polymers adopt at various locations within the nanoparticle. We find that the local microenvironments formed by the various polymer conformations promote preferential EEK solubilization within specific regions of the NP. This demonstrates that these microenvironments are key in controlling drug storage locations within nanoparticles, supporting the rational design of nanoparticles for therapeutic applications.

Electroactive Molecularly Imprinted Polymer Nanoparticles (eMIPs) for Label-free Detection of Glucose: Toward Wearable Monitoring.

The diagnosis of diabetes mellitus (DM) affecting 537 million adults worldwide relies on invasive and costly enzymatic methods that have limited stability. Electroactive polypyrrole (PPy)-based molecularly imprinted polymer nanoparticles (eMIPs) have been developed that rival the affinity of enzymes whilst being low-cost, highly robust, and facile to produce. By drop-casting eMIPs onto low-cost disposable screen-printed electrodes (SPEs), sensors have been manufactured that can electrochemically detect glucose in a wide dynamic range (1 µm-10 mm) with a limit of detection (LOD) of 26 nm. The eMIPs sensors exhibit no cross reactivity to similar compounds and negligible glucose binding to non-imprinted polymeric nanoparticles (eNIPs). Measurements of serum samples of diabetic patients demonstrate excellent correlation (>0.93) between these eMIPs sensor and the current gold standard Roche blood analyzer test. Finally, the eMIPs sensors are highly durable and reproducible (storage >12 months), showcasing excellent robustness and thermal and chemical stability. Proof-of-application is provided via measuring glucose using these eMIPs sensor in a two-electrode configuration in spiked artificial interstitial fluid (AISF), highlighting its potential for non-invasive wearable monitoring. Due to the versatility of the eMIPs that can be adapted to virtually any target, this platform technology holds high promise for sustainable healthcare applications via providing rapid detection, low-cost, and inherent robustness.

A Proof-of-Concept Study on the Theranostic Potential of 177 Lu-labeled Biocompatible Covalent Polymer Nanoparticles for Cancer Targeted Radionuclide Therapy.

Theranostic nanomedicine combined bioimaging and therapy probably rises more helpful and interesting opportunities for personalized medicine. In this work, 177 Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation (177 Lu-DOTA-PEG-CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that 177 Lu-DOTA-PEG-CPNs possess excellent bonding capacity with breast cancer cells (4T1), inhibiting the cell viability, leading to cell apoptosis, arresting the cell cycle, and upregulating the reactive oxygen species (ROS), which can be attributed to the good targeting ability of the nanocarrier and the strong relative biological effect of the radionuclide labelled compound. Single photon emission computed tomography/ computed tomography (SPECT/CT) imaging and in vivo biodistribution based on 177 Lu-DOTA-PEG-CPNs reveal that notable radioactivity accumulation at tumor site in murine 4T1 models with both intravenous and intratumoral administration of the prepared radiotracer. Significant tumor inhibition has been observed in mice treated with 177 Lu-DOTA-PEG-CPNs, of which the median survival was highly extended. More strikingly, 50 % of mice intratumorally injected with 177 Lu-DOTA-PEG-CPNs was cured and showed no tumor recurrence within 90 days. The outcome of this work can provide new hints for traditional nanomedicines and promote clinical translation of 177 Lu radiolabeled compounds efficiently.

Afterglow Performance of Phenylenevinylene-Based Semiconducting Polymer Nanoparticles Doped with Photosensitizers Containing Electron-Withdrawing Groups.

It is usually believed that doping with photosensitizers capable of generating singlet oxygen (1O2) plays a pivotal role in enhancing the afterglow performance of semiconducting polymer nanoparticles (SPNs). However, the effect of doping photosensitizer bearing electron-withdrawing groups has not been reported. Here we report the effect of doping with six photosensitizers possessing different electron-withdrawing groups on the afterglow performance of SPNs using poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (PF-MEHPPV) as substrate. It was found that the afterglow performance of SPNs was significantly influenced by doping with photosensitizers bearing electron-withdrawing groups. For the doped photosensitizers with strong electron-withdrawing groups, the stronger the electron-withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2 generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron-withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs. This work deepens the understanding of the design and synthesis of SPNs with different afterglow properties.

Full color control and patterned display device from cyan/magenta/yellow water-dispersed electrochromic polymer nanoparticles systems.

Electrochromic polymers (ECPs) have great application potential in flexible displays, and there is an increasing expectation of using green methods to form ECP films. Herein, we propose a modified microemulsion method to prepare cyan/magenta/yellow (C/M/Y) water-dispersed electrochromic polymer nanoparticles (WDEN) systems. Three polymer films (WDECP-C/M/Y) maintain similar electrochemical properties compared to their corresponding organic solvent-based polymer films. It is intriguing that WDECP-C/M/Y exhibit better electrochromic properties in terms of higher cycling stability (97.24%, 95.05%, and 52.84%, respectively) and faster switching time (0.94 s, 1.09 s, and 1.34 s for coloring time, respectively) due to the introduction of nanoparticles. In addition, it can achieve various desired colors by blending the C/M/Y WDEN systems in different ratios. The calculated chromaticity coordinates of the blending polymer films show close values to the experimental observation, and the calculated ΔE*abvalues range from 2.6 to 10.3, which may provide theoretical guidance for precisely color control. Finally, large-scale and patterned devices were assembled, which can achieve colored-to-colorless reversible electrochromism at a low driving voltage of 0-1.5 V. This work puts forward a universal and environmentally sustainable strategy to prepare WDEN systems, demonstrating their wide range of applications in display devices and electronic tags.

Activatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone Metastasis.

Bone metastases are secondary malignant tumors that commonly occur after the spread of advanced cancer cells. We herein report the activatable semiconducting polymer nanoinducers (ASPNFP) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPNFP are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles into singlet oxygen (1O2)-responsive nanocarriers. ASPNFP generate 1O2 under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of 1O2-responsive nanocarriers, allowing US-triggered releases of SPNP and Fe3O4 nanoparticles. SPNP decompose polyamines in tumor cells to produce acrolein and hydrogen peroxide (H2O2), in which H2O2 promotes Fenton reaction mediated by Fe3O4 nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (•OH). The generated acrolein, 1O2, and •OH can simultaneously amplify the oxidative damage. ASPNFP thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.

Deep Learning-Enabled Multiplexed Point-of-Care Sensor using a Paper-Based Fluorescence Vertical Flow Assay.

Multiplexed computational sensing with a point-of-care serodiagnosis assay to simultaneously quantify three biomarkers of acute cardiac injury is demonstrated. This point-of-care sensor includes a paper-based fluorescence vertical flow assay (fxVFA) processed by a low-cost mobile reader, which quantifies the target biomarkers through trained neural networks, all within <15 min of test time using 50 µL of serum sample per patient. This fxVFA platform is validated using human serum samples to quantify three cardiac biomarkers, i.e., myoglobin, creatine kinase-MB, and heart-type fatty acid binding protein, achieving less than 0.52 ng mL-1 limit-of-detection for all three biomarkers with minimal cross-reactivity. Biomarker concentration quantification using the fxVFA that is coupled to neural network-based inference is blindly tested using 46 individually activated cartridges, which shows a high correlation with the ground truth concentrations for all three biomarkers achieving >0.9 linearity and <15% coefficient of variation. The competitive performance of this multiplexed computational fxVFA along with its inexpensive paper-based design and handheld footprint makes it a promising point-of-care sensor platform that can expand access to diagnostics in resource-limited settings.

A comparative characterisation of commercially available lipid-polymer nanoparticles formed from model membranes.

From the discovery of the first membrane-interacting polymer, styrene maleic-acid (SMA), there has been a rapid development of membrane solubilising polymers. These new polymers can solubilise membranes under a wide range of conditions and produce varied sizes of nanoparticles, yet there has been a lack of broad comparison between the common polymer types and solubilising conditions. Here, we present a comparative study on the three most common commercial polymers: SMA 3:1, SMA 2:1, and DIBMA. Additionally, this work presents, for the first time, a comparative characterisation of polymethacrylate copolymer (PMA). Absorbance and dynamic light scattering measurements were used to evaluate solubilisation across key buffer conditions in a simple, adaptable assay format that looked at pH, salinity, and divalent cation concentration. Lipid-polymer nanoparticles formed from SMA variants were found to be the most susceptible to buffer effects, with nanoparticles from either zwitterionic DMPC or POPC:POPG (3:1) bilayers only forming in low to moderate salinity (< 600 mM NaCl) and above pH 6. DIBMA-lipid nanoparticles could be formed above a pH of 5 and were stable in up to 4 M NaCl. Similarly, PMA-lipid nanoparticles were stable in all NaCl concentrations tested (up to 4 M) and a broad pH range (3-10). However, for both DIBMA and PMA nanoparticles there is a severe penalty observed for bilayer solubilisation in non-optimal conditions or when using a charged membrane. Additionally, lipid fluidity of the DMPC-polymer nanoparticles was analysed through cw-EPR, showing no cooperative gel-fluid transition as would be expected for native-like lipid membranes.

Preparation of Well-Defined Fluorescent Nanoplastic Particles by Confined Impinging Jet Mixing.

Research on the origin, distribution, detection, identification, and quantification of polymer nanoparticles (NPs) in the environment and their possible impact on animal and human health is surging. For different types of studies in this field, well-defined reference materials or mimics are needed. While isolated reports on the preparation of such materials are available, a simple and broadly applicable method that allows for the production of different NP types with well-defined, tailorable characteristics is still missing. Here, we demonstrate that a confined impinging jet mixing process can be used to prepare colloidally stable NPs based on polystyrene, polyethylene, polypropylene, and poly(ethylene terephthalate) with diameters below < 100 nm. Different fluorophores were incorporated into the NPs, to allow their detection in complex environments. To demonstrate their utility and detectability, fluorescent NPs were exposed to J774A.1 macrophages and visualized using laser scanning microscopy. Furthermore, we modified the NPs in a postfabrication process and changed their shape from spherical to heterogeneous geometries, in order to mimic environmentally relevant morphologies. The methodology used here should be readily applicable to other polymers and payloads and thus a broad range of NPs that enable studies of their behavior, uptake, translocation, and biological end points in different systems.

Biocompatible conjugated polymer nanoparticles labeled with 225Ac for tumor endoradiotherapy.

Recently, endoradiotherapy based on actinium-225 (225Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, 111In/225Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) using 111In-DOTA-PEG-CPNs as nano probe indicates a prolonged retention of radiolabeled nanocarriers, which was consistent with the in vivo biodistribution examined by direct radiometry analysis. Significant inhibition of tumor growth has been observed in murine 4T1 models treated with 225Ac-DOTA-PEG-CPNs when compared to mice treated with PBS or DOTA-PEG-CPNs. The 225Ac-DOTA-PEG-CPNs group experienced no single death within 24 days with the median survival considerably extended to 35 days, while all the mice treated with PBS or DOTA-PEG-CPNs died at 20 days post injection. Additionally, the histopathology studies demonstrated no obvious side effects on healthy tissues after treatment with 225Ac-DOTA-PEG-CPNs. All these results reveal that the new 225Ac-labeled DOTA-PEG-CPNs is promising as paradigm for endoradiotherapy.

Electrochemical and thermal detection of allergenic substance lysozyme with molecularly imprinted nanoparticles.

Lysozyme (LYZ) is a small cationic protein which is widely used for medical treatment and in the food industry to act as an anti-bacterial agent; however, it can trigger allergic reactions. In this study, high-affinity molecularly imprinted nanoparticles (nanoMIPs) were synthesized for LYZ using a solid-phase approach. The produced nanoMIPs were electrografted to screen-printed electrodes (SPEs), disposable electrodes with high commercial potential, to enable electrochemical and thermal sensing. Electrochemical impedance spectroscopy (EIS) facilitated fast measurement (5-10 min) and is able to determine trace levels of LYZ (pM) and can discriminate between LYZ and structurally similar proteins (bovine serum albumin, troponin-I). In tandem, thermal analysis was conducted with the heat transfer method (HTM), which is based on monitoring the heat transfer resistance at the solid-liquid interface of the functionalized SPE. HTM as detection technique guaranteed trace-level (fM) detection of LYZ but needed longer analysis time compared to EIS measurement (30 min vs 5-10 min). Considering the versatility of the nanoMIPs which can be adapted to virtually any target of interest, these low-cost point-of-care sensors hold great potential to improve food safety.

Detecting phosphate using lysine-sensitized terbium coordination polymer nanoparticles as ratiometric luminescence probes.

Probes for detecting phosphate ions (Pi) are required for environmental monitoring and to protect human health. Here, novel ratiometric luminescent lanthanide coordination polymer nanoparticles (CPNs) were successfully prepared and used to selectively and sensitively detect Pi. The nanoparticles were prepared from adenosine monophosphate (AMP) and Tb3+, and lysine (Lys) was used as a sensitizer (through the antenna effect) to switch on Tb3+ luminescence at 488 and 544 nm while Lys luminescence at 375 nm was quenched because of energy transfer from Lys to Tb3+. The complex involved is here labeled AMP-Tb/Lys. Pi destroyed the AMP-Tb/Lys CPNs and therefore decreased the AMP-Tb/Lys luminescence intensity at 544 nm and increased the luminescence intensity at 375 nm at an excitation wavelength of 290 nm, meaning ratiometric luminescence detection was possible. The ratio between the luminescence intensities at 544 and 375 nm (I544/I375) was strongly associated with the Pi concentration between 0.1 and 6.0 µM, and the detection limit was 0.08 µM. The dual-emission reverse-change ratio luminescence sensing method can exclude environmental effects, so the proposed assay was found to be very selective. The method was successfully used to detect Pi in real water samples, and acceptable recoveries were found, suggesting that the method could be used in practice to detect Pi in water samples.

A novel ROS-Related chemiluminescent semiconducting polymer nanoplatform for acute pancreatitis early diagnosis and severity assessment.

Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease of the pancreas. Reactive oxygen species (ROS) play a key role in the occurrence and development of AP. With increasing ROS levels, the degree of oxidative stress and the severity of AP increase. However, diagnosing AP still has many drawbacks, including difficulties with early diagnosis and undesirable sensitivity and accuracy. Herein, we synthesized a semiconducting polymer nanoplatform (SPN) that can emit ROS-correlated chemiluminescence (CL) signals. The CL intensity increased in solution after optimization of the SPN. The biosafety of the SPN was verified in vitro and in vivo. The mechanism and sensitivity of the SPN for AP early diagnosis and severity assessment were evaluated in three groups of mice using CL intensity, serum marker evaluations and hematoxylin and eosin staining assessments. The synthetic SPN can be sensitively combined with different concentrations of ROS to produce different degrees of high-intensity CL in vitro and in vivo. Notably, the SPN shows an excellent correlation between CL intensity and AP severity. This nanoplatform represents a superior method to assess the severity of AP accurately and sensitively according to ROS related chemiluminescence signals. This research overcomes the shortcomings of AP diagnosis in clinical practice and provides a novel method for the clinical diagnosis of pancreatitis in the future.

Luminescence nanomaterials for biosensing applications.

Due to their capacity to immobilize more bioreceptor parts at reduced volumes, nanomaterials have emerged as potential tools for increasing the sensitivity to specific molecules. Furthermore, carbon nanotubes, gold nanoparticles, polymer nanoparticles, semiconductor quantum dots, nanodiamonds, and graphene are among the nanomaterials that are under investigation. Due to the fast development of this field of research, this review summarizes the classification of biosensors using the main receptors and design of biosensors. Numerous studies have concentrated on the manipulation of persistent luminescence nanoparticles (PLNPs) in biosensing, cell tracking, bioimaging, and cancer therapy due to the effective removal of autofluorescence interference from tissues and the ultra-long near-infrared afterglow emission. As luminescence has a unique optical property, it can be detected without constant external illumination, preventing autofluorescence and light dispersion through tissues. These successes have sparked an increasing interest in creating novel PLNP types with the desired superior properties and multiple applications. In this review, we emphasize the most recent developments in biosensing, imaging, and image-guided therapy whilst summarizing the research on synthesis methods, bioapplications, biomembrane modification, and the biosafety of PLNPs. Finally, the remaining issues and difficulties are examined together with prospective future developments in the biomedical application field.

Photothermal enhanced fluorescence quenching of Tb-norfloxacin for ultrasensitive human epididymal 4 detection.

A fluorescence quenching enhanced immunoassay has been developed to achieve ultrasensitive recognition of human epididymal 4 (HE4) modifying the fluorescence quencher. The carboxymethyl cellulose sodium-functionalized Nb2C MXene nanocomposite (CMC@MXene) was firstly introduced to quench the fluorescence signal of the luminophore Tb-Norfloxacin coordination polymer nanoparticles (Tb-NFX CPNPs). The Nb2C MXene nanocomposite as fluorescent nanoquencher inhibits the electron transfer between Tb and NFX to quench the fluorescent signal by coordinating the strongly electronegative carboxyl group on CMC with Tb (III) of Tb-NFX complex. Simultaneously, due to the superior photothermal conversion capability of CMC@MXene, the fluorescence signal has been further weakened by the photothermal effect driven non-radiative decay of the excited state under near-infrared laser irradiation. The constructed fluorescent biosensor based on CMC@MXene probe finally realized the enhanced fluorescence quenching effect, and achieved ultra-high sensitivity and selective detection of HE4, exhibiting a wide linear relationship with HE4 concentration on the logarithmic axis in the range of 10-5 to 10 ng/mL and a low detection limit of 3.3 fg/mL (S/N = 3). This work not only provides an enhanced fluorescent signal quenching method for the detection of HE4, but also provides novel insights for the design of fluorescent sensor toward different biomolecules.

High-efficiency fluorescent coordination polymer nanoparticles co-doped with Ce3+/Tb3+ ions for curcumin detection.

Curcumin (Cur) possesses diverse biological and pharmacologic effects. It is widely used as a food additive and therapeutic medicine. A study to determine a sensitive detection method for Cur is necessary and meaningful. In this work, double rare earth ions co-doped fluorescent coordination polymer nanoparticles (CPNPs) were developed for the Cur detection. The CPNPs were synthesized by using adenosine monophosphate (AMP) as bridge ligands via coordination self-assembly with Ce3+ and Tb3+. The AMP-Ce/Tb CPNPs exhibited the characteristic green fluorescence of Tb3+ and had high luminescence efficiency. Under the optimal conditions, the fluorescence intensity of AMP-Ce/Tb CPNPs could be significantly quenched by Cur. The fluorescence quenching extent at λex/λem of 300 nm/544 nm showed a good linear relationship with the Cur concentration in the range of 10 to 1000 nM. The detection limit was as low as 8.0 nM (S/N = 3). This method was successfully applied to the determination of Cur in real samples with satisfactory results. The luminescence mechanism of AMP-Ce/Tb CPNPs and the fluorescence quenching mechanism of the CPNPs by Cur were both examined.

Porous Zirconia Scaffolds Functionalized with Calcium Phosphate Layers and PLGA Nanoparticles Loaded with Hydrophobic Gentamicin.

Implant-related infections are a worldwide issue that is considered very challenging. Conventional therapies commonly end up failing; thus, new solutions are being investigated to overcome this problem. The in situ delivery of the drug at the implant site appears to be more sufficient compared to systemic antibiotic therapy. In this study, we manufactured porous zirconia scaffolds using the foam replication method. To improve their overall bioactivity, they were coated with a calcium phosphate (CaP) layer containing antibiotic-loaded degradable polymer nanoparticles (NPs) obtained by the double emulsion method to achieve the antibacterial effect additionally. Encapsulation efficiency (EE) and drug loading (DL) were superior and were equal to 99.9 ± 0.1% and 9.1 ± 0.1%, respectively. Scaffolds were analyzed with scanning electron microscopy, and their porosity was evaluated. The porosity of investigated samples was over 90% and resembled the microstructure of spongy bone. Furthermore, we investigated the cytocompatibility with osteoblast-like MG-63 cells and antimicrobial properties with Staphylococcus aureus. Scaffolds coated with a CaP layer were found non-toxic for MG-63 cells. Moreover, the presence of antibiotic-loaded nanoparticles had no significant influence on cell viability, and the obtained scaffolds inhibited bacteria growth. Provided processes of fabrication of highly porous zirconia scaffolds and surface functionalization allow minimizing the risk of implant-related infection.

Biocompatibility and Biological Effects of Surface-Modified Conjugated Polymer Nanoparticles.

Semiconductiong polymer nanoparticles (Pdots) have a wide range of applications in biomedical fields including biomolecular probes, tumor imaging, and therapy. However, there are few systematic studies on the biological effects and biocompatibility of Pdots in vitro and in vivo. The physicochemical properties of Pdots, such as surface modification, are very important in biomedical applications. Focusing on the central issue of the biological effects of Pdots, we systematically investigated the biological effects and biocompatibility of Pdots with different surface modifications and revealed the interactions between Pdots and organisms at the cellular and animal levels. The surfaces of Pdots were modified with different functional groups, including thiol, carboxyl, and amino groups, named Pdots@SH, Pdots@COOH, and Pdots@NH2, respectively. Extracellular studies showed that the modification of sulfhydryl, carboxyl, and amino groups had no significant effect on the physicochemical properties of Pdots, except that the amino modification affected the stability of Pdots to a certain extent. At the cellular level, Pdots@NH2 reduced cellular uptake capacity and increased cytotoxicity due to their instability in solution. At the in vivo level, the body circulation and metabolic clearance of Pdots@SH and Pdots@COOH were superior to those of Pdots@NH2. The four kinds of Pdots had no obvious effect on the blood indexes of mice and histopathological lesions in the main tissues and organs. This study provides important data for the biological effects and safety assessment of Pdots with different surface modifications, which pave the way for their potential biomedical applications.

Ultrarapid Microwave-Assisted Synthesis of Fluorescent Silver Coordination Polymer Nanoparticles and Its Application in Detecting Alkaline Phosphatase Activity.

Fluorescent silver coordination polymer nanoparticles (Ag-TPA CPNs) were synthesized using a combination of terephthalic acid (TPA) and silver nitrate via an ultrarapid microwave-assisted strategy within 15 min. The Ag-TPA CPNs displayed a high fluorescent quantum yield (QY = 20.19%) and large Stokes shift (~200 nm), with two emission peaks at 490 nm and 520 nm under an excitation wavelength of 320 nm. A fluorescent "turn-off" method using fluorescent Ag-TPA CPNs was applied to detect the alkaline phosphatase (ALP) activity on the basis of the ALP-catalyzed hydrolysis of ascorbic acid 2-phosphate (AA2P) to ascorbic acid (AA), and the AA product triggered the reduction of Ag+ ions into silver nanoparticles. The fluorescent lifetime of Ag-TPA CPNs decreased from 3.93 ms to 3.80 ms after the addition of ALP, which suggests that this fluorescent "turn-off" detection of ALP activity is a dynamic quenching process. The fluorescent intensity had a linear relationship with the concentration of ALP in the range of 0.2-12 mU/mL (r = 0.991) and with a limit of detection (LOD) of 0.07 mU/mL. It showed high selectivity in ALP detection towards metal ions and amino acids, as well as other enzymes such as horseradish peroxidase, glucose oxidase, tyrosinase, trypsin, lysozyme, and superoxides. When it was applied for the fluorescent "turn-off" detection of ALP activity in serum samples, mean recovery levels ranging from 99.5% to 101.2% were obtained, with relative standard deviations (RSDs) lower than 4% accuracy. Therefore, it is an efficient and accurate tool for analyzing ALP levels in biosamples.