Chemically Powered Nanomotors with Magnetically Responsive Function for Targeted Delivery of Exosomes.

Janus structure plays a crucial role in achieving chemically driven nanomotors with exceptional motion performance. However, Janus-structured chemically driven nanomotors with magnetic responsiveness are commonly fabricated by sputtering metal films. In the study, a self-assembly technique is employed to asymmetrically modify the surfaces of magnetic silica (SiO2@Fe3O4) nanoparticles with platinum nanoparticles, resulting in the formation of this kind nanomotors. Compared to platinum film, platinum nanoparticles exhibit a larger surface area and a higher catalytic activity. Hence, the nanomotors demonstrate improved diffusion capabilities at a significantly lower concentration (0.05%) of hydrogen peroxide (H2O2). Meanwhile, exosomes have gained attention as a potential tool for the efficient delivery of biological therapeutic drugs due to their biocompatibility. However, the clinical applications of exosomes are limited by their restricted tropism. The previously obtained nanomotors are utilized to deliver exosomes, greatly enhancing its targetability. The drug doxorubicin (DOX) is subsequently encapsulated within exosomes, acting as a representative drug model. Under the conditions of H2O2 concentration at the tumor site, the exosomes exhibited a significantly enhanced rate of entry into the breast cancer cells. The utilization of the nanomotors for exosomes presents a novel approach in the development of hybrid chemically and magnetically responsive nanomotors.

Neisseria gonorrhoeae Infection in Women Increases With Rising Gonococcal Burdens in Partners: Chlamydia Coinfection in Women Increases Gonococcal Burden.

BACKGROUND: Likelihood of Neisseria gonorrhoeae infection in women exposed to male sex partners with increasing N. gonorrhoeae burdens and enhancement by Chlamydia trachomatis is not defined. METHODS: We identified men with urethritis and their regular female sex partners. Exposure to N. gonorrhoeae burdens in men was compared in N. gonorrhoeae-infected versus -uninfected partners. Association of N. gonorrhoeae infection in women with burdens in male partners was estimated using logistic regression. Association of C. trachomatis coinfection and N. gonorrhoeae burdens in women adjusted for burdens in male partners was estimated by linear regression. RESULTS: In total, 1816 men were enrolled; 202 had ≥2 partners, 91 who confirmed monogamy and were enrolled; 77% were married. Seventy were partners of N. gonorrhoeae-infected men; 58 (83%) were N. gonorrhoeae infected, 26 (45%) C. trachomatis coinfected. Infected women had partners with 9.3-fold higher N. gonorrhoeae burdens than partners of uninfected women (P = .0041). Association of N. gonorrhoeae infection in women with upper quartiles of N. gonorrhoeae burdens in partners increased (odds ratios ≥ 2.97)compared to the first quartile (P = .032). N. gonorrhoeae burdens in C. trachomatis-coinfected women were 2.82-fold higher than in C. trachomatis-uninfected women (P = .036). CONCLUSIONS: N. gonorrhoeae infections increased in women whose partners were infected with higher N. gonorrhoeae burdens. C. trachomatis coinfection was associated with increased N. gonorrhoeae burdens in women.

Wearable SERS Sensor Based on Omnidirectional Plasmonic Nanovoids Array with Ultra-High Sensitivity and Stability.

Surface-enhanced Raman spectroscopy (SERS) is a promising technology for wearable sensors due to its fingerprint spectrum and high detection sensitivity. However, since SERS-activity is sensitive to both the distribution of "hotspots" and excitation angle, it is profoundly challenging to develop a wearable SERS sensor with high stability under various deformations during movements. Herein, inspired by omnidirectional light-harvesting of the compound eye of Xenos Peckii, a wearable SERS sensor is developed using omnidirectional plasmonic nanovoids array (OPNA), which is prepared by assembling a monolayer of metal nanoparticles into the artificial plasmonic compound-eye (APC). Specifically, APC is an interconnected frame containing omnidirectional "pockets" and acts as an "armour", not only rendering a broadband and omnidirectional enhancement of "hotspots" in the delicate nanoparticles array, but also maintaining an integrity of the "hotspots" against external mechanical deformations. Furthermore, an asymmetry super-hydrophilic pattern is fabricated on the surface of OPNA, endowing the hydrophobic OPNA with the ability to spontaneously extract and concentrate the analytes from sweat. Such an armored SERS sensor can enable the wearable and in situ analysis with high sensitivity and stability, exhibiting great potential in point-of-care analysis.

Triple-color fluorescence co-localization of PD-L1-overexpressing cancer exosomes.

Programed cell death ligand 1 (PD-L1) is a protein biomarker overexpressed on exosomes derived from tumor cells. It plays an important role in tumor diagnosis, screening, evaluation of therapeutic efficacy, and prognosis. In this study, a facile method is presented to detect PD-L1-overexpressing cancer exosomes with high specificity and sensitivity. First, gold nanospheres (GNSs) were attached to the bottom of an eight-well chambered slide by electrostatic adsorption, forming the detection substrate. Then, Cy5-labeled CD63 aptamers (i.e., the capture probes) were modified on the GNSs by Au-S bond. After adding samples containing target exosomes which were stained by membrane dyes DiI in advance, FAM-labeled PD-L1 aptamers (i.e., the immunoprobes) were added to recognize PD-L1 on the target exosomes. By triple-color fluorescence co-localization (TFC) of the Cy5, DiI, and FAM channels, highly sensitive and reliable detection of the PD-L1-overexpressing exosomes was achieved in the concentration range 7.78 × 101 to 7.78 × 104 particles/mL with a detection limit down to 6 particles/mL. The advantages of the proposed detection method include the following; first, the detection substrate is easy to prepare and convenient to clean. Second, the TFC strategy can completely exclude nonspecific reaction sites and thus significantly improves the accuracy. Such a facile and reliable detection method holds a great potential in exosome-based cancer theranostics. In this paper, we proposed a triple-color fluorescence co-localization (TFC) strategy to significantly improve the reliability of exosome detection and the detection substrate is easy to prepare and convenient to clean. In addition, the LOD is down to 6 particles/mL, which is quite low compared with other detection methods.

Simultaneous detection of multiple exosomal microRNAs for exosome screening based on rolling circle amplification.

Exosomal microRNAs (miRNAs) have attracted great attention as predictive and prognostic biomarkers of cancer. Profiling of miRNAs plays a key role in the effective diagnosis of cancers. However, simultaneous quantification of multiple miRNAs is challenging due to their homology and low abundance especially in exosomes. Here, we developed a sensitive detection method for multiple exosomal miRNAs with the help of rolling circle amplification (RCA). In contrast of the traditional ways, this method takes the advantages of both the multiplex sensing ability and the simplicity of RCA. Specifically, multiple exosomal miRNAs from different cell lines were replicated simultaneously through RCA and detected using designed molecular beacons (MBs). miRNA-21, miRNA-122 and miRNA-155 were chosen as the targets, which are overexpressed in cancers. Normalized fluorescence intensities of MB were used to imply the relative concentrations of these miRNAs. The obtained relative miRNAs expression levels could be used to distinguish the breast cancer exosome from normal one. If the varieties of the detected exosomal miRNAs are abundant enough, the concentration ratios of miRNAs could basically indicate the corresponding exosome and exosome screening could be realized. Such exosomal miRNA profiling and exosome screening can assist cancer diagnosis, which is promising in clinical application.

Mycoplasma genitalium in Symptomatic Male Urethritis: Macrolide Use Is Associated With Increased Resistance.

BACKGROUND: Mycoplasma genitalium (MG) causes symptomatic urethritis in men, and can infect alone or together with other sexually transmitted infection (STI) agents. METHODS: The prevalence of MG and other STIs was determined in 1816 men with symptomatic urethritis. Resistance of MG to macrolides and fluoroquinolones was determined by sequencing; the impact of recent antimicrobial usage on the distribution of MG single or mixed infections was determined. RESULTS: Overall, prevalence of MG infection was 19.7% (358/1816). Fifty-four percent (166/307) of MG infections occurred alone in the absence of other STI agents. Men with single MG infection self-administered or were prescribed antibiotics more often in the 30 days prior to enrollment than subjects with urethritis caused by MG coinfection (P < .0001). Higher rates (96.7%) of infection with macrolide resistance in MG were identified in men who had taken macrolides prior to enrollment (P < .03). Overall, 88.9% (303/341) of 23S ribosomal RNA (rRNA) genes contained mutations responsible for macrolide resistance; 89.5% (308/344) of parC and 12.4% (42/339) of gyrA genes had mutations responsible for fluoroquinolone resistance. Approximately 88% (270/308) of MG had combined mutations in 23S rRNA and parC genes; 10.4% (32/308) had mutations in all 3 genes. CONCLUSIONS: MG was the single pathogen identified in 11% of men with symptomatic urethritis. Overall, nearly 90% of MG infections were resistant to macrolides and fluoroquinolones. Men who took macrolides in the 30 days prior to enrollment had higher rates (97%) of macrolide-resistant MG. Resistance was associated with numerous mutations in 23SrRNA, parC, and gyrA genes.

Incidence of Severe and Nonsevere Pertussis Among HIV-Exposed and -Unexposed Zambian Infants Through 14 Weeks of Age: Results From the Southern Africa Mother Infant Pertussis Study (SAMIPS), a Longitudinal Birth Cohort Study.

BACKGROUND: Maternal vaccination with tetanus, reduced-dose diphtheria, and acellular pertussis vaccine (Tdap) could be an effective way of mitigating the high residual burden of infant morbidity and mortality caused by Bordetella pertussis To better inform such interventions, we conducted a burden-of-disease study to determine the incidence of severe and nonsevere pertussis among a population of Zambian infants. METHODS: Mother-infant pairs were enrolled at 1 week of life, and then seen at 2- to 3-week intervals through 14 weeks of age. At each visit, nasopharyngeal (NP) swabs were obtained from both, and symptoms were catalogued. Using polymerase chain reaction (PCR) to identify cases, and a severity scoring system to triage these into severe/nonsevere, we calculated disease incidence using person-time at risk as the denominator. RESULTS: From a population of 1981 infants, we identified 10 with clinical pertussis, for an overall incidence of 2.4 cases (95% confidence interval [CI], 1.2-4.2) per 1000 infant-months and a cumulative incidence of 5.2 cases (95% CI, 2.6-9.0) per 1000 infants. Nine of 10 cases occurred within a 3-month window (May-July 2015), with highest incidence between birth and 6 weeks of age (3.5 cases per 1000 infant-months), concentrated among infants prior to vaccination or among those who had only received 1 dose of Diphtheria Tetanus whole cell Pertussis (DTwP). Maternal human immunodeficiency virus (HIV) modestly increased the risk of infant pertussis (risk ratio, 1.8 [95% CI, .5-6.9]). Only 1 of 10 infant cases qualified as having severe pertussis. The rest presented with the mild and nonspecific symptoms of cough, coryza, and/or tachypnea. Notably, cough durations were long, exceeding 30 days in several cases, with PCRs repeatedly positive over time. CONCLUSIONS: Pertussis is circulating freely among this population of Zambian infants but rarely presents with the classical symptoms of paroxysmal cough, whooping, apnea, and cyanosis. Maternal HIV appears to increase the risk, while lack of effective exposure to DTwP increased the risk.

One-step detection of nanoplastics in aquatic environments using a portable SERS chessboard substrate.

Nanoplastics present a significant hazard to both the environment and human health. However, the development of rapid and sensitive analysis techniques for nanoplastics is limited by their small size, lack of specificity, and low concentrations. In this study, a surface-enhanced Raman scattering (SERS) chessboard substrate was introduced as a multi-channel platform for the pre-concentration and detection of nanoplastics, achieved by polydomain aggregating silver nanoparticles (PASN) on a hydrophilic and a punched hydrophobic PVDF combined filter membrane. Through a straightforward suction filtration process, nanoplastics were captured by the PASN gap in a single step for subsequent SERS detection, while excess moisture was promptly eliminated from the filter membrane. The PASN-based SERS chessboard substrate, benefiting from the enhanced electromagnetic (EM) field, effectively discriminated polystyrene (PS) nanoplastics ranging in size from 30 nm to 1000 nm. Furthermore, this substrate demonstrated favorable repeatability (RSD of 8.6 %), high sensitivity with a detection limit of 0.001 mg/mL for 100 nm of PS nanoplastics, and broad linear detection ranges spanning from 0.001 to 0.5 mg/mL (R2 = 0.9916). Additionally, the SERS chessboard substrate enabled quantitative analysis of nanoplastics spiked in tap and lake water samples. Notably, the entire pre-concentration and detection procedure required only 3 µL of sample and could be completed within 1 min. With the accessibility of portable detection instruments and the ability to prepare substrates on demand, the PASN-based SERS chessboard substrate is anticipated to facilitate the establishment of a comprehensive global nanoplastics map.

Metal nanoprobe-decorated all-inorganic perovskite nanocrystal-based fluorescence-linked immunosorbent assay for the detection of tumor-derived exosomes.

All-inorganic perovskite nanocrystals (CsPbX3 NCs, X = Cl, Br, I) are promising fluorescence materials for biological detection due to their excellent optical properties. However, there is still a challenge to obtain stable CsPbX3 NCs with more biofunctions. Here, we proposed a distinct strategy by absorbing the functionalized metal nanoprobes onto the phospholipid encapsulated CsPbX3 NCs to achieve CsPbX3-metal hybrids as probes for the detection of tumor-derived exosomes. Here, the metal nanoprobes have two functions: first, it endows phospholipid encapsulated CsPbX3 NCs with recognition ability; second, it avoids the fluorescence quenching of CsPbX3 NCs during the biological modification process by using metal nanoparticles as a bridge to connect with CsPbX3 NCs and various biomolecules. The obtained CPXD-AD exhibited a bright fluorescence signal, narrow full width at half-maximum (FWHM), and high specificity. Under optimal conditions, the CPXD-AD-based fluorescence-linked immunosorbent assay (FLISA) was successfully established and used for both qualitative and quantitative detection of tumor-derived exosomes.

L-type lectin receptor-like kinase OsCORK1 as an important negative regulator confers copper stress tolerance in rice.

Copper (Cu) is vital for plant growth but becomes toxic in excess, posing potential threats to human health. Although receptor-like kinases (RLKs) have been studied in plant response to abiotic stresses, their roles in Cu stress response remain poorly understood. Therefore, we aimed to evaluate Cu toxicity effects on rice and elucidate its potential molecular mechanisms. Specifically, rice lectin-type RLK OsCORK1 (Copper-response receptor-like kinase 1) function in Cu stress response was investigated. RNA sequencing and expression assays revealed that OsCORK1 is mainly expressed in roots and leaves, and its expression was significantly induced by Cu stress time- and dose-dependently. Kinase activity assays demonstrated OsCORK1 as a Mn2+-preferred functional kinase. Genetically, OsCORK1 gene-edited mutants exhibited increased tolerance to Cu stress and reduced Cu accumulation compared to the wild type (WT). Conversely, OsCORK1 overexpression compromised the Cu stress tolerance observed in OsCORK1 gene-edited mutants. OsCORK1 gene-edited mutants slightly damaged the root tips compared to the WT under Cu stress. Furthermore, OsCORK1 was demonstrated to modulate Cu stress tolerance by mainly altering cell wall components, particularly lignin, in rice. Overall, OsCORK1 is an important negative regulator of Cu stress tolerance, providing a potential gene target to reduce Cu pollution in rice production.

Water-dispersed CsPbBr3 nanocrystals for single molecule localization microscopy with high location accuracy for targeted bioimaging.

Single-molecule localization microscopy (SMLM) is one of the most promising super-resolution imaging techniques for visualizing ultrasmall cellular structures. Here, water-dispersed perovskite CsPbBr3 nanocrystals (CsPbBr3 NCs) fabricated by a one-step mechanochemical method are explored as a SMLM fluorophore for bioimaging. Due to their ultrahigh photoluminescence quantum yield (PLQY), inherent frequent fluorescence blinking, proper duty cycle and long-term photostability, an extremely high location precision of ∼3 nm was achieved, a sixfold enhancement than those reported previously. In addition, the spatial resolution of a SMLM image depends on the size of CsPbBr3 NCs, which is approximately 23 nm. Two closely spaced CsPbBr3 NCs with a gap of 40 nm can be clearly distinguished in the SMLM image. More importantly, unlike most perovskite quantum dots (QDs), one-step mechanochemically prepared CsPbBr3 NCs can retain their excellent fluorescence characteristics even after surface biofunctionalization, greatly reducing the current limitations of perovskite QDs on bioimaging. As an example, cell-derived exosomes (30-150 nm in diameter) labeled with CsPbBr3 NCs were easily identified by SMLM. In addition, after being functionalized with biotin, targeted SMLM imaging of the nuclear lamina or cell membranes of cells was achieved with an enhanced resolution. This work may open up a promising avenue to expand the field of perovskite QD-based SMLM to bioimaging with a high location accuracy.

Wavelength Tunable Aqueous CsPbBr3-Based Nanoprobes with Ultrahigh Photostability for Targeted Super-Resolution Bioimaging.

Single molecule localization microscopy (SMLM) is indispensable in the visualization of cellular microstructures. However, current SMLM imaging materials, from organic fluorophores to quantum dots, still lack the requirement of increasing need for multiple targets of interest due to their broad emission. Here, by one-step encapsulating hydrophilic cesium lead bromide perovskite nanocrystals (CsPbBr3 NCs) into functionalized polyethylene glycol (PEG), a core-shell nanocomposite of CsPb(Cl(1-x)/Brx)3@PEG (0 < x < 1) was presented as a wavelength-tunable fluorescent probe with the narrow full width at half-maximum (fwhm) as 11 nm. The layer of functionalized PEG endows CsPbBr3 NCs with a broad spectral tunability from 521 to 431 nm, superior photostability for several years, and the ability to be further surface functionalized. The CsPb(Cl(1-x)/Brx)3@PEG exhibits a sub-10 nm localization precision and 10-fold enhanced spatial resolution. Using exosomes with small sizes less than 150 nm as the imaging target, CsPb(Cl(1-x)/Brx)3@PEG realized the distinction of two adjacent exosomes by SMLM. Moreover, after being modified with biotin, CsPb(Cl(1-x)/Brx)3@PEG was universally used for SMLM imaging of cellular microstructures. The excellent photostability and narrow fwhm indicated that such a CsPbBr3-based nanoprobe has great potential as a commercial dye for multitarget super-resolution bioimaging applications.

A Programmable Plasmonic Gas Microsystem for Detecting Arbitrarily Combinated Volatile Organic Compounds (VOCs) with Ultrahigh Resolution.

For gas sensors, the ultrasensitive and highly selective detection of multiple components is of great significance in a wide range of applications extending from environment to healthcare, which is still a long-term challenge due to the single sensing mechanism of most sensors. Here, we combine the advantages of microfluidic chips and surface-enhanced Raman spectroscopy (SERS) spectra to fabricate a smart single-chip for simultaneously detecting an arbitrary combination of VOCs that incorporates different detection units, working on either a physisorption or chemisorption mechanism. Full integration of microfluidic and multiplex nanostructure components on one chip permits programmable design for sensing multifarious volatile compounds, and enables on-chip signal amplifications with increased reproducibility. As a proof-of-principle experiment, we demonstrate the simultaneous identification of 9 different gases that belong to aromatic compounds, aldehydes, ketones, or sulfides in one mixture, with high sensitivity (ppb level), high selectivity, and high robustness (error ∼8%). We further evaluated the application of our universal gas sensor in two scenarios including indoor air pollution monitoring and exhaled breath-based disease diagnosis. We expect that our design will improve the various practical applications of gas sensors.

Eliminating nonspecific binding sites for highly reliable immunoassay via super-resolution multicolor fluorescence colocalization.

Non-specific adsorption in immunoassays has always been a major problem that affects the reliability of assay results. Despite the emergence of various methods that can reduce nonspecific adsorption, a universal and effective method to reduce the influence of nonspecific adsorption is still lacking. Hence, we propose here an optical super-resolution imaging based immunoassay strategy, named super-resolution multicolor fluorescence colocalization (SR-MFC), which can generate a low false-positive rate. Taking advantages of the high spatial resolution of single-molecule localization microscopy (SMLM), SR-MFC can directly visualize the assay results and thus effectively exclude the nonspecific binding sites. In other words, even if nonspecific interactions do happen, SR-MFC ensures that the nonspecific reaction sites are visualized and abandoned, which has never been achieved before. To verify its practicability, exosomes, which are important cancer biomarkers, were used as model targets and detected using SR-MFC. Compared with common immunofluorescence assay, the accuracy and reliability of the detection results are greatly improved. The detection limit of exosomes was 38 particles per µL. More importantly, the SR-MFC method can also be generalized for the detection of other biomarkers (e.g. proteins, DNAs, etc.), which is a significant and promising new strategy for immunoassay based diagnosis.

A Ti2N MXene-based nanosystem with ultrahigh drug loading for dual-strategy synergistic oncotherapy.

The exploration of MXenes, especially nitride MXenes, in the field of theranostic nanomedicine is still in its infancy. Here, towards synergistic chemo-photothermal oncotherapy, we demonstrate the first kind of 2D titanium nitride (Ti2N) MXene-based nanosystem (Ti2N@oSi) for dual-strategy synergistic oncotherapy. The unique structure of Ti2N nanosheets endows the drug carriers with an ultrahigh loading capacity of 796.3% and an excellent NIR photothermal conversion efficiency of 41.6% for chemo-photothermal therapy. After being coated with a biodegradable organosilica shell, the Ti2N@oSi nanocarriers show excellent characteristics of tumor targeting, pH/glutathione/photothermal-responsive drug release and dual-drug combination chemotherapy. Both in vitro and in vivo therapeutic evaluations demonstrate the pronounced tumor growth inhibition effect and superior biocompatibility of Ti2N@oSi nanocarriers. The excellent drug loading ability, photothermal conversion ability and surface modifiability of Ti2N open up new opportunities for tumor microenvironment-targeted synergistic oncotherapy. This work is supposed to broaden the application of MXenes in nanomedicine and, particularly, provide the first sight to the biomedical application of nitride MXenes.

Ti3C2Tx MXene-Loaded 3D Substrate toward On-Chip Multi-Gas Sensing with Surface-Enhanced Raman Spectroscopy (SERS) Barcode Readout.

Gas sensors lie at the heart of various fields ranging from medical to environmental sciences, and the demand of gas sensors is instantly expanding. However, in the face of complex gas samples, how to maintain high sensitivity while performing multiplex detection still puzzles the researchers. Here, by introducing Ti3C2Tx MXene into a microfluidic gas sensor with a three-dimensional (3D) transferable SERS substrate, a powerful gas sensor having both multiplex detecting ability and high sensitivity is demonstrated. The employ of MXene endows the sensor with a universal high adsorption efficiency for various gases while the generation of in situ gas vortices in the sophisticated nanomicro structure extends the molecule residence time in SERS-active area, both leading to the increased sensitivity. In the proof-of-concept experiment, a limit of detection (LOD) of 10-50 ppb was achieved for three typical volatile organic compounds (VOCs) according to the intrinsic SERS signals of gas molecules. Besides, the well-designed periodic 3D structure solves the general repeatability problem of SERS substrates. In addition, the detailed composition of gas mixture was revealed using classic least-square analysis (CLS) with an average accuracy of 90.6%. Further, a chromatic barcode was developed based on the results of CLS to read out the complex composition of samples visually.

Epidemiological and Clinical Observations of Gonococcal Infections in Women and Prevention Strategies.

Neisseria gonorrhoeae is rapidly developing antimicrobial resistance. There is an urgent need for an effective gonococcal vaccine. In this study we examined epidemiological and clinical factors associated with gonorrhea in a cohort of women exposed to men with gonococcal urethritis attending the National Center for STD Control clinic in Nanjing, China, to understand the natural history and the risk factors for gonorrhea in this vulnerable population. This analysis will help identify the best target populations for vaccination, which is essential information for the development of vaccine strategies. We observed that 75% of the women in our cohort yielded a N. gonorrhoeae positive culture (infected women) and reported multiple sexual exposures to their infected partner. Infected women were younger than exposed but uninfected women. Contrary to the general belief that gonorrhea is asymptomatic in most women, 68% of the infected women acknowledged symptoms during their STD clinic visit, and overt inflammatory responses were detected upon medical examination in 88% of subjects. Other sexually transmitted infections were detected in 85% of subjects. This study confirmed that N. gonorrhoeae infections are underdiagnosed in women and, consequentially, untreated. Thus, our analysis reinforces the need to establish strategies for gonococcal prevention through the determination of the target population for a gonococcal vaccine.

Ultra-sensitive surface enhanced Raman spectroscopy sensor for in-situ monitoring of dopamine release using zipper-like ortho-nanodimers.

Accurate quantitative detection of dopamine (DA) in blood is essential for the early diagnosis and the pathogenesis analysis of dopaminergic dysfunction, which still remains a great challenge because of the extremely low concentration in patients. Using our previously reported DNA-assisted synthesis of ortho-nanodimers (DaSON) strategy, a microfluidic surface enhanced Raman spectroscopy (SERS) biosensor for the ultrasensitive and reliable detection of DA in serum was demonstrated by modifying SERS probes with DA aptamers in a specific orientation to form zipper-like ortho-nanodimers. The uniform 1-nm gap in zipper-like ortho-nanodimers endows the SERS sensor with ultrahigh sensitivity and high accuracy for the detection of DA. The limit of detection is as low as 10 aM in phosphate buffer saline and 10 fM in serum, which is about two orders of magnitude lower than that of previous methods. Using a single microfluidic chip containing a 3D cell culture unit, quantitatively in-situ monitoring of extracellular DA released from living neurons under different medications was first realized. Quantification of DA in human blood samples was also achieved with the recoveries ranging from 87.5% to 123.7%. Given the difficulty of DA quantification in complex physiological samples, our developed SERS sensor provides an appealing tool for in-vitro investigating of neurological processes and clinical examination of dopaminergic disorders.

Black Phosphorus-Based Drug Nanocarrier for Targeted and Synergetic Chemophotothermal Therapy of Acute Lymphoblastic Leukemia.

As one of the novel two-dimensional nanomaterials, black phosphorus nanosheets (BP NS) have been proven to be excellent carrier materials for drugs, owing to their fine optical properties and biocompatibility. In this work, a composite drug nanocarrier based on BP NS is proposed, which can perform a synergetic and targeted chemophotothermal therapy of acute lymphoblastic leukemia (ALL). First, BP NS were prepared by an improved liquid exfoliation technique. Then, polyethylene glycol (PEG) was modified on the surfaces of BP NS through electrostatic adsorption. Drug molecules can also be loaded onto the BP NS via electrostatic adsorption. The PEG layer can effectively protect the interior BP NS from water and air to enhance their physiological stability. The obtained PEGylated BP NS (BP NS@PEG) not only demonstrated an excellent photothermal conversion efficiency and photothermal stability but also exhibited a good pH and photothermal dual-responsive drug release behavior. In addition, the BP NS@PEG were further modified with Sgc8 aptamers through covalent bonding. The aptamers provided an efficient specificity toward ALL cells (CCRF-CEM) and greatly increased the endocytosis of the nanocarriers through a receptor-mediated manner, which can further improve the therapeutic effect. Hence, the presented BP NS-based multifunctional nanocarrier can achieve a targeted and synergetic chemophotothermal therapy of ALL, which shows a promising potential in improving the curative efficiency.

Lead Halide Perovskite Nanocrystals-Phospholipid Micelles and Their Biological Applications: Multiplex Cellular Imaging and in Vitro Tumor Targeting.

Lead halide perovskite nanocrystals (NCs) are promising optical materials in many fields. However, their poor moisture stability, significant toxicity, and difficulty to be further functionalized greatly hinder their applications in bioimaging. Here, a universal strategy is demonstrated by simply encapsulating CsPbX3 (X = Cl, Br, I) NCs into phospholipids to achieve CsPbX3-phospholipid micelles (CsPbX3@phospholipid) as probes for multiplex encoding cellular imaging or tumor-targeted imaging. The layer of phospholipids endows CsPbX3 NCs with superior water-resistant characteristics, the ability to be further biofunctionalized, and greatly improved biocompatibility. The CsPbX3@phospholipid micelles exhibited strong luminescence with narrow fwhm in water for more than four months. Specifically, even after being modified with folic acid, the bright fluorescence of the micelles was well retained, which were employed for the targeting of Hela cells. Finally, the greatly reduced toxicity of the CsPbX3@phospholipid micelles was verified using HeLa cells and zebrafish as in vitro and in vivo models, respectively.