Plasmonic Gold Nanostar-Based Probes with Distance-Dependent Plasmon-Enhanced Fluorescence for Ultrasensitive DNA Methyltransferase Assay.

The ultrasensitive DNA methyltransferase (Dam MTase) assay is of high significance for biomedical research and clinical diagnosis because of its profound effect on gene regulation. However, detection sensitivity is still limited by shortcomings, including photobleaching and weak signal intensities of conventional fluorophores at low concentrations. Plasmonic nanostructures with ultrastrong electromagnetic fields and fluorescence enhancement capability that can overcome these intrinsic defects hold great potential for ultrasensitive bioanalysis. Herein, a silica-coated gold nanostars (Au NSTs@SiO2)-based plasmon-enhanced fluorescence (PEF) probe with 20 "hot spots" was developed for ultrasensitive detection of Dam MTase. Here, the Dam Mtase assay was achieved by detecting the byproduct PPi of the rolling circle amplification reaction. It is worth noting that, benefiting from the excellent fluorescence enhancement capability of Au NSTs originating from their 20 "hot spots", the detection limit of Dam Mtase was reduced by nearly 105 times. Moreover, the proposed Au NST-based PEF probe enabled versatile evaluation of Dam MTase inhibitors as well as endogenous Dam MTase detection in GW5100 and JM110 Escherichia coli cell lysates, demonstrating its potential in biomedical analysis.

Light and endogenous enzyme triggered plasmonic antennas for accurate subcellular molecular imaging with enhanced spatial resolution.

Developing accurate tumor-specific molecular imaging approaches holds great potential for evaluating cancer progression. However, traditional molecular imaging approaches still suffer from restricted tumor specificity due to the "off-tumor" signal leakage. In this work, we proposed light and endogenous APE1-triggered plasmonic antennas for accurate tumor-specific subcellular molecular imaging with enhanced spatial resolution. Light activation ensures subcellular molecular imaging and endogenous enzyme activation ensures tumor-specific molecular imaging. In addition, combined with the introduction of plasmon enhanced fluorescence (PEF), off-tumor signal leakage at the subcellular level was effectively reduced, resulting in the significantly enhanced discrimination ratio of tumor/normal cells (∼11.57-fold) which is better than in previous reports, demonstrating great prospects of these plasmonic antennas triggered by light and endogenous enzymes for tumor-specific molecular imaging at the subcellular level.

Development and Validation of an Automated Classification System for Osteonecrosis of the Femoral Head Using Deep Learning Approach: A Multicenter Study.

BACKGROUND: Accurate classification can facilitate the selection of appropriate interventions to delay the progression of osteonecrosis of the femoral head (ONFH). This study aimed to perform the classification of ONFH through a deep learning approach. METHODS: We retrospectively sampled 1,806 midcoronal magnetic resonance images (MRIs) of 1,337 hips from 4 institutions. Of these, 1,472 midcoronal MRIs of 1,155 hips were divided into training, validation, and test datasets with a ratio of 7:1:2 to develop a convolutional neural network model (CNN). An additional 334 midcoronal MRIs of 182 hips were used to perform external validation. The predictive performance of the CNN and the review panel was also compared. RESULTS: A multiclass CNN model was successfully developed. In internal validation, the overall accuracy of the CNN for predicting the severity of ONFH based on the Japanese Investigation Committee classification was 87.8%. The macroaverage values of area under the curve (AUC), precision, recall, and F-value were 0.90, 84.8, 84.8, and 84.6%, respectively. In external validation, the overall accuracy of the CNN was 83.8%. The macroaverage values of area under the curve, precision, recall, and F-value were 0.87, 79.5, 80.5, and 79.9%, respectively. In a human-machine comparison study, the CNN outperformed or was comparable to that of the deputy chief orthopaedic surgeons. CONCLUSION: The CNN is feasible and robust for classifying ONFH and correctly locating the necrotic area. These findings suggest that classifying ONFH using deep learning with high accuracy and generalizability may aid in predicting femoral head collapse and clinical decision-making.

Enzymatically Activated Autonomous-Motion DNAzyme Signal Amplification Strategy for Tumor Cell-Specific Molecular Imaging with Improved Spatial Specificity.

Strategies for achieving tumor-specific molecular imaging based on signal amplification hold great potential for evaluating the risk of tumor metastasis and progression. However, traditional amplification strategies are still constrained with limited tumor specificity because of the off-tumor signal leakage. Herein, an endogenous enzyme-activated autonomous-motion DNAzyme signal amplification strategy (E-DNAzyme) was rationally designed for tumor-specific molecular imaging with improved spatial specificity. The sensing function of E-DNAzyme can be specifically activated by the overexpressed apurinic/apyrimidinic endonuclease 1 (APE1) in the cytoplasm of tumor cells instead of normal cells, ensuring the tumor cell-specific molecular imaging with improved spatial specificity. Of note, benefiting from the target analogue-triggered autonomous motion of the DNAzyme signal amplification strategy, the detection limit can be decreased by approx. ∼7.8 times. Moreover, the discrimination ratio of tumor/normal cells of the proposed E-DNAzyme was ∼3.44-fold higher than the traditional amplification strategy, indicating the prospect of this universal design for tumor-specific molecular imaging.

Review of the Pathogenesis, Diagnosis, and Management of Osteoradionecrosis of the Femoral Head.

Osteoradionecrosis (ORN) of the femoral head is an important issue for orthopedists and radiologists in clinical practice. With the rapid development of technological advances in radiation therapy and the improvement in cancer survival rates, the incidence of ORN is rising, and there is an unmet need for basic and clinical research. The pathogenesis of ORN is complex, and includes vascular injury, mesenchymal stem cell injury, bone loss, reactive oxygen species, radiation-induced fibrosis, and cell senescence. The diagnosis of ORN is challenging and requires multiple considerations, including exposure to ionizing radiation, clinical manifestations, and findings on physical examination and imaging. Differential diagnosis is essential, as clinical symptoms of ORN of the femoral head can resemble many other hip conditions. Hyperbaric oxygen therapy, total hip arthroplasty, and Girdlestone resection arthroplasty are effective treatments, each with their own advantages and disadvantages. The literature on ORN of the femoral head is incomplete and there is no criterion standard or clear consensus on management. Clinicians should gain a better and more comprehensive understanding on this disease to facilitate its early and better prevention, diagnosis, and treatment. This article aims to review the pathogenesis, diagnosis, and management of osteoradionecrosis of the femoral head.

Automatic detection of early osteonecrosis of the femoral head from various hip pathologies using deep convolutional neural network: a multi-centre study.

PURPOSE: The aim of this study was to develop a deep convolutional neural network (DCNN) for detecting early osteonecrosis of the femoral head (ONFH) from various hip pathologies and evaluate the feasibility of its application. METHODS: We retrospectively reviewed and annotated hip magnetic resonance imaging (MRI) of ONFH patients from four participated institutions and constructed a multi-centre dataset to develop the DCNN system. The diagnostic performance of the DCNN in the internal and external test datasets was calculated, including area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, and F1 score, and gradient-weighted class activation mapping (Grad-CAM) technique was used to visualize its decision-making process. In addition, a human-machine comparison trial was performed. RESULTS: Overall, 11,730 hip MRI segments from 794 participants were used to develop and optimize the DCNN system. The AUROC, accuracy, and precision of the DCNN in internal test dataset were 0.97 (95% CI, 0.93-1.00), 96.6% (95% CI: 93.0-100%), and 97.6% (95% CI: 94.6-100%), and in external test dataset, they were 0.95 (95% CI, 0.91- 0.99), 95.2% (95% CI, 91.1-99.4%), and 95.7% (95% CI, 91.7-99.7%). Compared with attending orthopaedic surgeons, the DCNN showed superior diagnostic performance. The Grad-CAM demonstrated that the DCNN placed focus on the necrotic region. CONCLUSION: Compared with clinician-led diagnoses, the developed DCNN system is more accurate in diagnosing early ONFH, avoiding empirical dependence and inter-reader variability. Our findings support the integration of deep learning systems into real clinical settings to assist orthopaedic surgeons in diagnosing early ONFH.

Fluorescence-Enhanced Dual-Driven "OR-AND" DNA Logic Platform for Accurate Cell Subtype Identification.

Developing an endogenous stimuli-responsive and ultrasensitive DNA sensing platform that contains a logic gate biocomputation for precise cell subtype identification holds great potential for disease diagnosis and prognostic estimation. Herein, a fluorescence-enhanced "OR-AND" DNA logic platform dual-driven by intracellular apurinic/apyrimidinic endonuclease 1 (APE 1) or a DNA strand anchored on membrane protein Mucin 1 (MUC 1) for sensitive and accurate cell subtype identification was rationally designed. The recognition toehold of the traditional activated probe (TP) was restrained by introducing a blocking sequence containing an APE 1 cleavable site (AP-site) that can be either cleaved by APE 1 or replaced by Mk-apt, ensuring the "OR-AND" gated molecular imaging for cell subtype identification. It is worth noting that this "OR-AND" gated design can effectively avoid the missing logical computation caused by membrane protein heterogeneous spatial distribution as a single input. In addition, a benefit from the excellent plasmon-enhanced fluorescence (PEF) ability of Au NSTs is that the detection limit can be decreased by nearly 165 times. Based on this, not only different kinds of MCF-7, HepG2, and L02 cells, but also different breast cancer cell subtypes, including malignant MCF-7, metastatic MDA-MB-231, and nontumorigenic MCF-10A cells, can be accurately identified by the proposed "OR-AND" gated DNA logic platform, indicating the prospect of this simple and universal design in accurate cancer screening.

Optimal Timing of Anterior Cruciate Ligament Reconstruction in Patients With Anterior Cruciate Ligament Tear: A Systematic Review and Meta-analysis.

Importance: The timing of surgery has been regarded as a key factor in anterior cruciate ligament reconstruction (ACLR), and early vs delayed ACLR remains a controversial topic. Objective: To synthesize up-to-date published data from randomized clinical trials (RCTs) comparing early vs elective delayed ACLR for patients with ACL deficiency, in terms of clinical outcomes and complications. Data Sources: The PubMed, Cochrane Library, and Web of Science databases were systematically searched until September 9, 2022. Study Selection: All published RCTs comparing clinical and functional outcomes and complications associated with early ACLR vs elective delayed ACLR. Data Extraction and Synthesis: Two reviewers independently extracted relevant data and assessed the methodological quality following the PRISMA guidelines. Main Outcomes and Measures: Due to the clinical heterogeneity, the random-effects model was preferred. The primary outcomes were functional outcomes and complications. The Mantel-Haenszel test was used to evaluate dichotomous variables and the inverse variance method was used to assess continuous variables. Results: This meta-analysis included 972 participants in 11 RCTs stratified by follow-up duration. The following factors did not differ between early and delayed ACLR: operative time (mean difference, 4.97; 95% CI, -0.68 to 10.61; P = .08), retear (OR, 1.52; 95% CI, 0.52-4.43; P = .44), and infection (OR, 3.80; 95% CI, 0.77-18.79; P = .10). There were also no differences between groups in range of motion, knee laxity, International Knee Documentation Committee (IKDC rating scale), and Tegner score. IKDC score (mean difference, 2.77; 95% CI, 1.89-3.66; P < .001), and Lysholm score at 2-year follow-up (mean difference, 2.61; 95% CI, 0.74-4.48; P = .006) significantly differed between early and delayed ACLR. In addition, the timing of surgery was redefined in the included RCTs and subgroup analyses were performed, which validated the robustness of the principal results. Conclusion and Relevance: This systematic review and meta-analysis found that early ACLR was not superior to delayed ACLR in terms of most factors analyzed, except for IKDC and Lysholm scores. This information should be available to patients with ACL deficiency and clinicians as part of the shared decision-making process of treatment selection.

DNA Computation-Modulated Self-Assembly of Stimuli-Responsive Plasmonic Nanogap Antennas for Correlated Multiplexed Molecular Imaging.

Nanogap antennas with strong electromagnetic fields of the "hot spot" in the gap region of two adjacent particles that can significantly improve the optical properties of fluorophores hold great potential for ultrasensitive bioanalysis. Herein, a DNA computation-mediated self-assembly of Au NBP dimer-based plasmonic nanogap antennas was designed for imaging of intracellular correlated dual disease biomarkers. It is worth noting that with the benefit from the electromagnetic fields of the "hot spot" in the gap region and strand displacement amplification, the fluorescence intensity can be enhanced ∼14.7-fold by Au NBP dimer-based plasmonic nanogap antennas. In addition, the AND-gate sensing mechanism was confirmed through monitoring the response of three designed nAP-PH1, m-PH1, and PH1 probes, the fluorescence recovery in different cell lines (Hela and L02), and inhibitor-treated cells, respectively. Furthermore, thanks to the "dual keys" activation design, such an "AND-gate" sensing manner can be used for ultrasensitive correlated multiplexed molecular imaging, demonstrating its feasible prospect in correlated multiplexed molecular imaging.

Spatiotemporally Controlled Ultrasensitive Molecular Imaging Using a DNA Computation-Mediated DNAzyme Platform.

Programming ultrasensitive and stimuli-responsive DNAzyme-based probes that contain logic gate biocomputation hold great potential for precise molecular imaging. In this work, a DNA computation-mediated DNAzyme platform that can be activated by 808 nm NIR light and target c-MYC was designed for spatiotemporally controlled ultrasensitive AND-gated molecular imaging. Particularly, the sensing and recognition function of the traditional DNAzyme platform was inhibited by introducing a blocking sequence containing a photo-cleavable linker (PC-linker) that can be indirectly cleaved by 808 nm NIR light and thus enables the AND-gated molecular imaging. According to the responses toward three designed SDz, nPC-SDz, and m-SDz DNAzyme probes, the fluorescence recovery in diverse cell lines (MCF-7, HeLa, and L02) and inhibitor-treated cells was investigated to confirm the AND-gated sensing mechanism. It is worth noting that thanks to the strand displacement amplification and the ability of gold nanopyramids (Au NBPs) to enhance fluorescence, the fluorescence intensity increased by ∼7.9 times and the detection limit decreased by nearly 40.5 times. Moreover, false positive signals can be also excluded due to such AND-gated design. Furthermore, such a designed "AND-gate" sensing manner can also be applied to spatiotemporally controlled ultrasensitive in vivo molecular imaging, indicating its promising potential in precise biological molecular imaging.

pH Programmed Optical Sensor Arrays for Cancer Plasma Straightforward Discrimination Based on Protein-Responsive Patterns.

Optical cross-reactive sensor arrays inspired by the mammalian olfactory system that can realize straightforward discrimination of plasma from cancer patients hold great potential for point-of-care diseases diagnostics. Herein, a pH programmed fluorescence sensor array based on protein-responsive patterns was designed for straightforward discrimination of different types of cancer plasma. It is worth noting that plasma discrimination can be realized only by programming one nanomaterial using different pH values, which greatly simplifies the programmable design of the sensor array, making it an important highlight of this work. In addition, the mechanism of the pH programmed fluorescence sensor array for protein responsiveness was systematically investigated through molecular docking simulation, fluorescence resonance energy transfer (FRET), and fluorescence lifetime experiments. Most importantly, not only can the differences between plasma from healthy people and and from patients with different cancer species including gastric cancer, liver cancer, breast cancer, and cervical cancer be discriminated by this pH programmed fluorescence sensor array, but also the blind test of unknown plasma samples can be well identified with 100% accuracy, indicating its promising prospect in clinical application.

Osteoradionecrosis of the Hip, a Troublesome Complication of Radiation Therapy: Case Series and Systematic Review.

Background: Osteoradionecrosis of the hip is a serious complication of radiotherapy that is easily overlooked by physicians and patients in the early stages. There are relatively few reports on this subject, so there is no clear scientific consensus for the pathogenesis, early diagnosis, and clinical treatment of hip osteoradionecrosis. In this paper, we report two cases of hip osteoradionecrosis and systematically review the related literature. Case Presentation: We report two cases of hip osteoradionecrosis. One patient successfully underwent total hip arthroplasty in our hospital and recovered well postoperatively. Another patient although we offered a variety of surgical options for this patient, the patient was worried that the bone loss would lead to poor prosthesis fixation, resulting in prosthesis loosening and infection, and therefore ultimately refused surgical treatment. Conclusion: With the development of radiological techniques, the incidence of hip osteoradionecrosis is decreasing year by year, but early diagnosis and rational treatment remain challenging. The effects of non-surgical treatment are limited. Early prevention, early detection, and early intervention are crucial to delay or prevent the emergence of more serious complications.

Optically Programmable Plasmon Enhanced Fluorescence-Catalytic Hairpin Assembly Signal Amplification Strategy for Spatiotemporally Precise Imaging.

Signal amplification strategies with spatiotemporally high sensitivity can provide more accurate information and hold great promise for improving the accuracy of disease diagnosis. Herein, a 808 nm near-infrared (NIR) light-activated plasmon enhanced fluorescence-catalytic hairpin assembly (PEF-CHA) signal amplification strategy was proposed for spatiotemporally controllable precise imaging of miRNA in vitro and in vivo with ultrasensitivity. The proposed 808 nm NIR light-activated PEF-CHA signal amplification strategy is constructed through combining up-conversion photocontrol and PEF technologies with CHA. It is worth noting that the laser irradiation-induced overheating effect could be effectively alleviated by using Nd3+-sensitized upconversion nanoparticles (UCNPs) to convert 808 nm NIR light to ultraviolet (UV) light, which is almost nondestructive to cells or tissues. In addition, nonspecific activation as well as false positive signals can be effectively avoided. Moreover, the detection limit can be reduced by approximate 38 times thanks to the high sensitivity of the proposed strategy. Furthermore, we demonstrate that the 808 nm NIR light-activated PEF-CHA signal amplification strategy can be expanded to sensitive and activatable imaging of intratumoral miRNAs in living mice, showing feasible prospects for precise biological and medical analysis.

Slipped capital femoral epiphysis with hypopituitarism in adults: A case report and literature review.

RATIONALE: Slipped capital femoral epiphysis (SCFE) is a common disease in pediatric orthopedics. Most research on SCFE has focused on high-risk groups or the whole population, and studies focusing on adult SCFE patients are rare. In the present study, we report the case of an adult patient with SCFE. PATIENT CONCERN: A 37-year-old man presented to our clinic with persistent pain that was poorly localized to both hips, groin regions, and thighs for more than 1 year. DIAGNOSES: A bilateral hip X-ray examination was performed, and the femoral epiphyses were found to be unfused on both sides. Low levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), triiodothyronine (T3), thyroxine (T4), follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone, and high levels of thyroid-stimulating hormone, prolactin, and cortisol. INTERVENTIONS: Hormone-substitution therapies (levothyroxine sodium to treat hypothyroidism and testosterone enanthate to treat hypogonadism) were prescribed. Total hip arthroplasty was performed to treat femoral epiphysis slippage. OUTCOMES: After 6 months of postoperative follow-up, the patient's gait improved significantly, and bilateral hip pain was relieved. LESSONS: When treating adults with SCFE, clinicians must be alert to endocrine disorders. Comprehensive imaging evaluation is crucial for the accurate diagnosis and selection of an appropriate treatment.

From Passive Signal Output to Intelligent Response: "On-Demand" Precise Imaging Controlled by Near-Infrared Light.

"On-demand" accurate imaging of multiple intracellular miRNAs will significantly improve the detection reliability and accuracy. However, the "always-active" design of traditional multicomponent detection probes enables them to passively recognize and output signals as soon as they encounter targets, which will inevitably impair the detection accuracy and, inevitably, result in false-positive signals. To address this scientific problem, in this work, we developed a near-infrared (NIR) light-activated multicomponent detection intelligent nanoprobe for spatially and temporally controlled on-demand accurate imaging of multiple intracellular miRNAs. The proposed intelligent nanoprobe is composed of a rationally designed UV light-responsive triangular DNA nano sucker (TDS) and upconversion nanoparticles (UCNPs), named UCNPs@TDS (UTDS), which can enter cells autonomously through endocytosis and enable remote regulation of on-demand accurate imaging for multiple intracellular miRNAs using NIR light illumination at a chosen time and place. It is worth noting that the most important highlight of the UTDS we designed in this work is that it can resist nonspecific activation as well as effectively avoid false-positive signals and improve the accuracy of imaging of multiple intracellular miRNAs. Moreover, distinguishing different kinds of cell lines with different miRNA expressions levels can be also achieved through this NIR light-activated intelligent UTDS, showing feasible prospects in precise imaging and disease diagnosis.

Primary nonkeratinizing squamous cell carcinoma of the scapular bone: A case report.

BACKGROUND: Squamous cell carcinoma (SCC) of bone is usually caused by metastasis from the lungs, bladder, or other sites. Primary SCC of bone most frequently involves the skull bones, and primary involvement of other sites in the skeletal system is extremely rare. To date, only three such cases have been reported, which makes the diagnosis, treatment, and prognosis of this disease a challenge. CASE SUMMARY: A 76-year-old Chinese man presented to our hospital with nonspecific pain and limited mobility in the right shoulder for 4 mo. He underwent three-dimensional computed tomography reconstruction and magnetic resonance imaging of the right shoulder, which revealed an osteolytic destructive lesion in the right scapula with invasion into the surrounding muscles and soft tissues. Ultrasound-guided core needle biopsy detected a malignant tumor, and immunohistochemical analysis revealed a poorly differentiated SCC. Wide excision of the right scapular bone was performed, and pathological examination of the surgical specimen confirmed the diagnosis. At the last follow-up examination within 2 years, the patient was doing well with the pain significantly relieved in the right shoulder. CONCLUSION: Primary SCC of bone is extremely rare at sites other than the skull. Clinicians must exhaust all available means for the diagnosis of primary SCC of the bone, so greater attention can be paid to its timely and effective management. Regular and adequate follow-up is essential to help rule out metastasis and judge the prognosis.

More Symmetrical "Hot Spots" Ensure Stronger Plasmon-Enhanced Fluorescence: From Au Nanorods to Nanostars.

Plasmon-enhanced fluorescence (PEF) is considered to be a powerful signal amplification technology to overcome intrinsic shortcomings of photobleaching and brightness of the traditional fluorescent dyes. Nevertheless, exploitation of PEF-based probes for bioimaging application is still at a very early stage. In this work, a simple but powerful gold nanostar (Au NST)@SiO2-based PEF probe with 20 symmetric "hot spots" was developed for highly sensitive "lighting up" in situ imaging of intracellular microRNAs (miRNAs). By regulating the thickness of the silica shell, the distance between Au NSTs and fluorescent dyes was controlled, and the optimum fluorescence enhancement (21-fold) was obtained with the silica shell thickness of approximately 22 nm. Thanks to the 20 more powerful "hot spots" that can produce stronger localized electric fields, the Au NST-based PEF probe exhibits stronger PEF effects than the traditional plasmonic nanostructures such as gold nanorods (Au NRs), gold nanobipyramids (Au NBPs), and triangular gold nanoprisms (Au NPRs), resulting in high sensitivity and improved detection limit (LOD) of 0.21 pM for miRNA-21 analysis. Moreover, not only cancer cells (MCF-7 and Hela) and normal cells (L02) with distinct miRNA-21 expression levels can be discriminated but also tumor cells in co-cultured mixtures can be recognized, indicating its promising potential in clinical diagnosis.

Two-Dimensional Metalloporphyrinic Framework Nanosheet-Based Dual-Mechanism-Driven Ratiometric Electrochemiluminescent Biosensing of Protein Kinase Activity.

A dual-mechanism-driven ratiometric electrochemiluminescent (ECL) biosensor was developed for the ultrasensitive detection of protein kinase activity, which was based on a competitive catalytic reaction and resonance energy transfer (RET) by assembling gold nanoparticles (GNPs) on two-dimensional (2D) porphyrinic metal-organic framework (MOF) nanosheets. In this work, an ECL catalytic reaction competing for dissolved O2 proceeded between 2D copper-based zinc porphyrinic MOF (Cu-TCPP(Zn)) nanosheets and luminol. Meanwhile, the cathodic ECL of singlet oxygen (1O2), derived from the electrocatalytic reaction of 2D Cu-TCPP(Zn), would be reduced by the assembled GNPs due to RET, while the anodic emission of luminol could be enhanced by GNPs with excellent electrocatalytic activity. With the detection of protein kinase A (PKA) as an example, this dual-mechanism-driven ECL biosensor exhibited a broad linear range (0.005-5.0 U mL-1) and a sensitive detection limit (0.0037 U mL-1). Compared with the traditional single-mechanism-driven sensing strategies, the developed dual-mechanism-driven ratiometric ECL biosensor may provide an effective method for the design of green and ultrasensitive ECL sensors.

Aggregation-induced emission based one-step "lighting up" sensor array for rapid protein identification.

Based on the distinct fingerprint-like fluorescence responses generated by different electrostatic and hydrophobic interactions between three kinds of self-designed water-soluble aggregation-induced emission (AIE) fluorogens (AIEgens) and proteins, a fast responsive (10 min) and one-step "lighting up" fluorescent sensor array for rapid protein discrimination was developed.

Core-Shell Multifunctional Nanomaterial-Based All-in-One Nanoplatform for Simultaneous Multilayer Imaging of Dual Types of Tumor Biomarkers and Photothermal Therapy.

Versatile all-in-one nanoplatforms that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable for efficient tumor diagnosis and treatment. Herein, we have developed a novel core-shell multifunctional nanomaterial-based all-in-one nanoplatform composed of gold nanobipyramids@polydopamine (Au NBPs@PDA) and gold nanoclusters (Au NCs) for simultaneous in situ multilayer imaging of dual types of tumor biomarkers (using a single-wavelength excitation) with different intracellular spatial distributions and fluorescence-guided photothermal therapy. The competitive combination between target transmembrane glycoprotein mucin1 (MUC1) and its aptamer caused Au NCs (620 nm) labeled with MUC1 aptamer to detach from the surface of Au NBPs@PDA, turning on the red fluorescence. Meanwhile, the hybridization between microRNA-21 (miRNA-21) and its complementary single-stranded DNA triggered the green fluorescence of Au NCs (515 nm). Based on this, simultaneous in situ multilayer imaging of dual types of tumor biomarkers with different intracellular spatial distributions was achieved. In addition, the potential of Au NBPs@PDA/Au NCs was also confirmed by simultaneous multilayer in situ imaging within not only three cell lines (MCF-7, HepG2, and L02 cells) with different expression levels of MUC1 and miRNA-21 but also cancer cells treated with different inhibitors. Moreover, the remarkable photothermal properties of Au NBPs@PDA resulted in the more efficient killing of cancer cells, demonstrating the great promise of the all-in-one nanoplatform for accurate diagnosis and tumor therapy.