Chaotropic Effect-Induced Sol-Gel Transition and Radical Stabilization for Bacterially Sensitive Near-Infrared Photothermal Therapy.

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.

Platelet Membrane Coated Cu9S8-SNAP for Targeting NIR-II Mild Photothermal Enhanced Chemodynamic/Gas Therapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive and uncommon subtype of breast cancer with a poor prognosis. It is crucial to prioritise the creation of a nanotherapeutic method that is highly selective and actively targeting TNBC. This study explores a new nanosystem, Cu9S8-SNAP@PM (C-S@P), composed of Cu9S8-SNAP coated with a platelet membrane (PM). The purpose of this nanosystem is to cure TNBC using multimodal therapy. The utilisation of PM-coated nanoparticles (NPs) enables active targeting, leading to the efficient accumulation of C-S@P within the tumour. The Cu9S8 component within these NPs serves the potential to exert photothermal therapy (PTT) and chemodynamic therapy (CDT). Simultaneously, the S-Nitroso-N-Acetylvanicillamine (SNAP) component enables nitric oxide (NO) gas therapy (GT). Furthermore, when exposed to NIR-II laser light, Cu9S8 not only increases the temperature of the tumour area for PTT, but also boosts CDT and stimulates the release of NO through thermal reactions to improve the effectiveness of GT. Both in vitro and in vivo experimental results validate that C-S@P exhibits minimal side effects and represents a multifunctional nano-drug targeted at tumors for efficient treatment. This approach promises significant potential for TNBC therapy and broader applications in oncology.

Mucus-Penetrating Nanoassembly as Potential Oral Phototherapeutic Formulation against Multi-Drug Resistant Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection presents increasing challenges to antibiotic therapies in limited penetration through gastric mucus, multi-drug resistance (MDR), biofilm formation, and intestinal microflora dysbiosis. To address these problems, herein, a mucus-penetrating phototherapeutic nanomedicine (RLs@T780TG) against MDR H. pylori infection is engineered. The RLs@T780TG is assembled with a near-infrared photosensitizer T780T-Gu and an anionic component rhamnolipids (RLs) for deep mucus penetration and light-induced anti-H. pylori performances. With optimized suitable size, hydrophilicity and weak negative surface, the RLs@T780TG can effectively penetrate through the gastric mucus layer and target the inflammatory site. Subsequently, under irradiation, the structure of RLs@T780TG is disrupted and facilitates the T780T-Gu releasing to target the H. pylori surface and ablate multi-drug resistant (MDR) H. pylori. In vivo, RLs@T780TG phototherapy exhibits impressive eradication against H. pylori. The gastric lesions are significantly alleviated and intestinal bacteria balance is less affected than antibiotic treatment. Summarily, this work provides a potential nanomedicine design to facilitate in vivo phototherapy in treatment of H. pylori infection.

Croconaine-based NIR-II fluorescence imaging-guided tumor photothermal therapy induces long-term antitumor immune memory.

Photothermal therapy (PTT) for cancers guided by optical imaging has recently shown great potential for precise diagnosis and efficient therapy. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence imaging (FLI) is highly desirable owing to its good spatial and temporal resolution, deep tissue penetration, and negligible tissue toxicity. Organic small molecules are attractive as imaging and treatment agents in biomedical research because of their low toxicity, fast clearance rate, diverse structures, ease of modification, and excellent biocompatibility. Various organic small molecules have been investigated for biomedical applications. However, there are few reports on the use of croconaine dyes (CRs), especially NIR-II emission CRs. To our knowledge, there have been no prior reports of NIR-II emissive small organic photothermal agents (SOPTAs) based on CRs. Herein, we report a croconaine dye (CR-TPE-T)-based nanoparticle (CR NP) with absorption and fluorescence emission in the NIR-I and NIR-II windows, respectively. The CR NPs exhibited intense NIR absorption, outstanding photothermal properties, and good biological compatibility. In vivo studies showed that CR NPs not only achieved real-time, noninvasive NIR-II FLI of tumors, but also induced significant tumor ablation with laser irradiation guided by imaging, without apparent side effects, and promoted the formation of antitumor immune memory in a colorectal cancer model. In addition, the CR NPs displayed efficient inhibition of breast tumor growth, improved longevity of mice and triggered efficient systemic immune responses, which further inhibited tumor metastasis to the lungs. Our study demonstrates the great potential of CRs as therapeutic agents in the NIR-II region for cancer diagnosis.

Impact of C-reactive Protein on Anticoagulation Monitoring in Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective single-center cohort study. SETTING: University-affiliated tertiary care academic medical center. PARTICIPANTS: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

Impact of inflammation and steroids on anti-coagulation in children supported on a ventricular assist device.

Critically ill pediatric patients supported on ventricular assist devices (VADs) are increasingly being anticoagulated on bivalirudin, but with difficulty monitoring anticoagulation. Activated partial thromboplastin time (aPTT) has recently been shown to poorly correlate with bivalirudin plasma concentrations, while dTT had excellent correlation. However, aPTT is the more common monitoring test and dTT testing is rarely used. In addition, effects of frequent clinical VAD scenarios (such as inflammation) on the accuracy of aPTT and dTT testing remains uncertain. We reviewed the effects of clinical scenarios (infection/inflammation, chylothorax, and steroids administration) on anticoagulation monitoring in 10 pediatric VAD patients less than 3 years at Cincinnati Children's Hospital Medical Center from 10/27/2020 to 5/6/2022 using bivalirudin for anticoagulation. There were 16 inflammation/infection, 3 chylothorax, and 6 steroids events. Correlation between dTT and aPTT was significantly lower after infection/inflammation, with dTT increasing prior to inflammation/infection while aPTT remained unchanged. In addition, steroids are administered to VAD patients to reduce inflammation and thus additionally stabilize anticoagulation. However, this anticoagulation stabilization effect was reflected more accurately by dTT compared to aPTT. In children requiring VAD support utilizing bivalirudin anticoagulation, inflammation/infection is a common occurrence resulting in anticoagulation changes that may be more accurately reflected by dTT as opposed to aPTT.

Application of Photoactive Compounds in Cancer Theranostics: Review on Recent Trends from Photoactive Chemistry to Artificial Intelligence.

According to the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC), the number of cancer cases and deaths worldwide is predicted to nearly double by 2030, reaching 21.7 million cases and 13 million fatalities. The increase in cancer mortality is due to limitations in the diagnosis and treatment options that are currently available. The close relationship between diagnostics and medicine has made it possible for cancer patients to receive precise diagnoses and individualized care. This article discusses newly developed compounds with potential for photodynamic therapy and diagnostic applications, as well as those already in use. In addition, it discusses the use of artificial intelligence in the analysis of diagnostic images obtained using, among other things, theranostic agents.

Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.

Accumulative Rolling Mg/PLLA Composite Membrane with Lamellar Heterostructure for Enhanced Bacteria Inhibition and Rapid Bone Regeneration.

Developing composite materials with optimized mechanics, degradation, and bioactivity for bone regeneration has long been a crucial mission. Herein, a multifunctional Mg/Poly-l-lactic acid (Mg/PLLA) composite membrane based on the "materials plain" concept through the accumulative rolling (AR) method is proposed. Results show that at a rolling ratio of 75%, the comprehensive mechanical properties of the membrane in the rolling direction are self-reinforced significantly (elongation at break ≈53.2%, tensile strength ≈104.0 MPa, Young's modulus ≈2.13 GPa). This enhancement is attributed to the directional arrangement and increased crystallization of PLLA molecular chains, as demonstrated by SAXS and DSC results. Furthermore, the AR composite membrane presents a lamellar heterostructure, which not only avoids the accumulation of Mg microparticles (MgMPs) but also regulates the degradation rate. Through the contribution of bioactive MgMPs and their photothermal effect synergistically, the membrane effectively eliminates bacterial infection and accelerates vascularized bone regeneration both in vitro and in vivo. Notably, the membrane exhibits outstanding rat skull bone regeneration performance in only 4 weeks, surpassing most literature reports. In short, this work develops a composite membrane with a "one stone, four birds" effect, opening an efficient avenue toward high-performance orthopedic materials.

Dual-targeting multifunctional hyaluronic acid ligand-capped gold nanorods with enhanced endo-lysosomal escape ability for synergetic photodynamic-photothermal therapy of cancer.

Au nanorods (AuNRs) have attracted considerable interest as drug delivery systems because of their enhanced cell internalization and stronger drug-loading ability. In addition, the incorporation of photodynamic therapy (PDT) and photothermal therapy (PTT) into one nanosystem presents great promise to defect multiple drawbacks in cancer therapy. Herein, we fabricated a multifunctional and dual-targeting nanoplatform based on hyaluronic acid-grafted-(mPEG/triethylenetetramine-conjugated-lipoic acid/tetra(4-carboxyphenyl)porphyrin/folic acid) polymer ligand capped AuNRs (AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) for combined photodynamic-photothermal therapy of cancer. The prepared nanoparticles displayed high TCPP loading capacity and excellent stability in different biological media. Furthermore, AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) not only could produce a localized hyperthermia to conduct PTT, but also generate cytotoxic singlet oxygen (1 O2 ) to perform PDT under laser irradiation. Confocal imaging results disclosed that this nanoparticle endowing the specific function of polymeric ligand could enhance cellular uptake, accelerate endo/lysosomal escape, as well as produce higher reactive oxygen species. Importantly, this combination therapy strategy could also induce higher anticancer potential than PDT or PTT only against MCF-7 tumor cells in vitro. Therefore, this work presented an AuNRs-based therapeutic nanoplatform with great potential in dual-targeting and photo-induced combination therapy of cancer.

Enhanced mild-temperature photothermal therapy by pyroptosis-boosted ATP deprivation with biodegradable nanoformulation.

BACKGROUND: Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT. RESULTS: Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT. CONCLUSIONS: Our in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy.

Black phosphorus quantum dots camouflaged with platelet-osteosarcoma hybrid membrane and doxorubicin for combined therapy of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most prevalent primary malignant bone tumor. However, single-agent chemotherapy exhibits limited efficacy against OS and often encounters tumor resistance. Therefore, we designed and constructed an integrated treatment strategy of photothermal therapy (PTT) combined with chemotherapy and used a surface-encapsulated platelet-osteosarcoma hybrid membrane (OPM) that enhances circulation time and enables OS-specific targeting. RESULTS: The OPM functions as a shell structure, encapsulating multiple drug-loaded nanocores (BPQDs-DOX) and controlling the release rate of doxorubicin (DOX). Moreover, near-infrared light irradiation accelerates the release of DOX, thereby extending circulation time and enabling photostimulation-responsive release. The OPM encapsulation system improves the stability of BPQDs, enhances their photothermal conversion efficiency, and augments PTT efficacy. In vitro and ex vivo experiments demonstrate that BPQDs-DOX@OPM effectively delivers drugs to tumor sites with prolonged circulation time and specific targeting, resulting in superior anti-tumor activity compared to single-agent chemotherapy. Furthermore, these experiments confirm the favorable biosafety profile of BPQDs-DOX@OPM. CONCLUSIONS: Compared to single-agent chemotherapy, the combined therapy using BPQDs-DOX@OPM offers prolonged circulation time, targeted drug delivery, enhanced anti-tumor activity, and high biosafety, thereby introducing a novel approach for the clinical treatment of OS.

Dual receptor NIR-II organic nanoparticles for multimodal imaging guided tumor photothermal therapy.

The second near-infrared (NIR-II) fluorescence imaging has attracted continuous attention due to its excellent penetration depth and high spatial resolution. Compared with other fluorophores, NIR-II fluorophores, especially NIR-II organic small molecule fluorophores, are favored because of their controllable structure and good biocompatibility. In this study, we designed and synthesized an S-D-A-D-S type small molecule FEA. However, a new molecule was accidentally obtained in the process of synthesis, which was proved to be a double receptor (A-A) type small molecule, namely S-D-A-A-D-S type organic small molecule FEAA. Compared with FEA molecules, FEAA exhibits superior fluorescence performance and can effectively prevent fluorescence quenching. The fluorescence emission of its nanoparticles (NPs) reaches 1109 nm, extends to about 1400 nm, and has a Stokes shift of up to 472 nm. Subsequently, we realized fluorescence/photoacoustic dual-mode imaging (FI/PAI) of nude mouse liver, and finally effectively ablated 4T1 tumor by photothermal therapy (PTT). In general, FEAA NPs exhibit good fluorescence, photoacoustic, and photothermal effects, and are an excellent multifunctional NIR-II organic small molecule fluorophore. As far as we know, there are few reports on A-A type organic small molecules, most of which are cyanines or D-A-D type structures. Therefore, this study has good exploratory significance and reference value for the discovery of NIR-II fluorophores.

Using Ballistocardiogram and Impedance Plethysmogram for Minimal Contact Measurement of Blood Pressure Based on a Body Weight-Fat Scale.

Electronic health (eHealth) is a strategy to improve the physical and mental condition of a human, collecting daily physiological data and information from digital apparatuses. Body weight and blood pressure (BP) are the most popular and important physiological data. The goal of this study is to develop a minimal contact BP measurement method based on a commercial body weight-fat scale, capturing biometrics when users stand on it. The pulse transit time (PTT) is extracted from the ballistocardiogram (BCG) and impedance plethysmogram (IPG), measured by four strain gauges and four footpads of a commercial body weight-fat scale. Cuffless BP measurement using the electrocardiogram (ECG) and photoplethysmogram (PPG) serves as the reference method. The BP measured by a commercial BP monitor is considered the ground truth. Twenty subjects participated in this study. By the proposed model, the root-mean-square errors and correlation coefficients (r2s) of estimated systolic blood pressure and diastolic blood pressure are 7.3 ± 2.1 mmHg and 4.5 ± 1.8 mmHg, and 0.570 ± 0.205 and 0.284 ± 0.166, respectively. This accuracy level achieves the C grade of the corresponding IEEE standard. Thus, the proposed method has the potential benefit for eHealth monitoring in daily application.

Bioinspired Synthesis of Magnetic Nanoparticles Based on Iron Oxides Using Orange Waste and Their Application as Photo-Activated Antibacterial Agents.

Magnetic nanoparticles based on iron oxides (MNPs-Fe) have been proposed as photothermal agents (PTAs) within antibacterial photothermal therapy (PTT), aiming to counteract the vast health problem of multidrug-resistant bacterial infections. We present a quick and easy green synthesis (GS) to prepare MNPs-Fe harnessing waste. Orange peel extract (organic compounds) was used as a reducing, capping, and stabilizing agent in the GS, which employed microwave (MW) irradiation to reduce the synthesis time. The produced weight, physical-chemical features and magnetic features of the MNPs-Fe were studied. Moreover, their cytotoxicity was assessed in animal cell line ATCC RAW 264.7, as well as their antibacterial activity against Staphylococcus aureus and Escherichia coli. We found that the 50GS-MNPs-Fe sample (prepared by GS, with 50% v/v of NH4OH and 50% v/v of orange peel extract) had an excellent mass yield. Its particle size was ~50 nm with the presence of an organic coating (terpenes or aldehydes). We believe that this coating improved the cell viability in extended periods (8 days) of cell culture with concentrations lower than 250 µg·mL-1, with respect to the MNPs-Fe obtained by CO and single MW, but it did not influence the antibacterial effect. The bacteria inhibition was attributed to the plasmonic of 50GS-MNPs-Fe (photothermal effect) by irradiation with red light (630 nm, 65.5 mW·cm-2, 30 min). We highlight the superparamagnetism of the 50GS-MNPs-Fe over 60 K in a broader temperature range than the MNPs-Fe obtained by CO (160.09 K) and MW (211.1 K). Therefore, 50GS-MNPs-Fe could be excellent candidates as broad-spectrum PTAs in antibacterial PTT. Furthermore, they might be employed in magnetic hyperthermia, magnetic resonance imaging, oncological treatments, and so on.

Synergistic Nanomedicine: Photodynamic, Photothermal and Photoimmune Therapy in Hepatocellular Carcinoma: Fulfilling the Myth of Prometheus?

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, with high morbidity and mortality, which seriously threatens the health and life expectancy of patients. The traditional methods of treatment by surgical ablation, radiotherapy, chemotherapy, and more recently immunotherapy have not given the expected results in HCC. New integrative combined therapies, such as photothermal, photodynamic, photoimmune therapy (PTT, PDT, PIT), and smart multifunctional platforms loaded with nanodrugs were studied in this review as viable solutions in the synergistic nanomedicine of the future. The main aim was to reveal the latest findings and open additional avenues for accelerating the adoption of innovative approaches for the multi-target management of HCC. High-tech experimental medical applications in the molecular and cellular research of photosensitizers, novel light and laser energy delivery systems and the features of photomedicine integration via PDT, PTT and PIT in immuno-oncology, from bench to bedside, were introspected. Near-infrared PIT as a treatment of HCC has been developed over the past decade based on novel targeted molecules to selectively suppress cancer cells, overcome immune blocking barriers, initiate a cascade of helpful immune responses, and generate distant autoimmune responses that inhibit metastasis and recurrences, through high-tech and intelligent real-time monitoring. The process of putting into effect new targeted molecules and the intelligent, multifunctional solutions for therapy will bring patients new hope for a longer life or even a cure, and the fulfillment of the myth of Prometheus.

Functionalization of and through Melanin: Strategies and Bio-Applications.

A unique feature of nanoparticles for bio-application is the ease of achieving multi-functionality through covalent and non-covalent functionalization. In this way, multiple therapeutic actions, including chemical, photothermal and photodynamic activity, can be combined with different bio-imaging modalities, such as magnetic resonance, photoacoustic, and fluorescence imaging, in a theragnostic approach. In this context, melanin-related nanomaterials possess unique features since they are intrinsically biocompatible and, due to their optical and electronic properties, are themselves very efficient photothermal agents, efficient antioxidants, and photoacoustic contrast agents. Moreover, these materials present a unique versatility of functionalization, which makes them ideal for the design of multifunctional platforms for nanomedicine integrating new functions such as drug delivery and controlled release, gene therapy, or contrast ability in magnetic resonance and fluorescence imaging. In this review, the most relevant and recent examples of melanin-based multi-functionalized nanosystems are discussed, highlighting the different methods of functionalization and, in particular, distinguishing pre-functionalization and post-functionalization. In the meantime, the properties of melanin coatings employable for the functionalization of a variety of material substrates are also briefly introduced, especially in order to explain the origin of the versatility of melanin functionalization. In the final part, the most relevant critical issues related to melanin functionalization that may arise during the design of multifunctional melanin-like nanoplatforms for nanomedicine and bio-application are listed and discussed.

Evaluation of Prothrombin Time and Activated Partial Thromboplastin Time in Native and Citrated Whole Blood in Hispaniolan Amazon Parrots (Amazona ventralis) With a Handheld Point-of-Care Analyzer.

Objective assessment of coagulation in birds is difficult, and traditional methods of measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT) with the use of mammalian reagents have not been validated in birds. Avian-specific reagents must be prepared from brain extract and are not practical for clinical use. The objective of this investigation was to determine whether the InSight qLabs point-of-care analyzer (Micropoint Biotechnologies Inc, Guangdong, China) could measure PT and aPTT in Hispaniolan Amazon parrots (Amazona ventralis) in native and citrated whole blood, and whether the values obtained correlated with clinical appearance and basic hematologic and biochemical parameters from the bird. The qLabs analyzer was able to measure aPTT reliably, but not PT. Activated partial thromboplastin time of citrated blood was significantly different from the aPTT measured from native whole blood (P < 0.001). On the basis of this study, the qLabs machine may be used to measure aPTT, but clinical application between avian species requires further research.

Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.

Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.

Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer.

BACKGROUND: Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. METHODS: We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. RESULTS: Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. CONCLUSION: This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.