Endovascular treatment of symptomatic severe intracranial atherosclerotic stenosis with a novel intracranial dedicated drug-eluting stent: a more effective treatment approach.

Background: Endovascular treatment of severe intracranial atherosclerotic stenosis (ICAS) using coronary drug-eluting stents (DESs) significantly reduces the risk of in-stent restenosis (ISR) and stroke recurrence. However, there are few reports regarding the treatment of ICAS with intracranial dedicated DES. Herein, we present our experience with the feasibility, safety, and medium-term follow-up outcomes of a novel intracranial DES, named NOVA stent, in patients with symptomatic severe ICAS (≥70%). Methods: From December 2021 to May 2022, patients with symptomatic severe ICAS who underwent implantation of the NOVA stent in our institution were retrospectively analyzed for procedural results, perioperative complications, imaging and clinical follow-up outcomes. Results: Twenty-four patients, 16 (66.7%) with anterior circulation lesions and 8 (33.3%) with posterior circulation lesions, were enrolled. All patients with intracranial ICA (n = 6), middle cerebral artery (n = 10), basilar artery (n = 3), intracranial vertebral artery (n = 3), and the vertebrobasilar junction (n = 2) stenosis were treated successfully using NOVA stents. The severity of stenosis ranged from 75 to 96% (mean 85.9%) before treatment and this was reduced to 0 to 20% (mean 8.6%) immediately after stent placement. Symptomatic distal embolism occurred in one case; however, there were no other perioperative complications. The mean follow-up duration was 12.2 ± 1.06 months. No symptomatic ischemic events occurred during follow-up. Follow-up cerebral angiography was performed in 22 of 24 patients (91.7%), and significant ISR occurred in one patient (4.2%). Conclusion: Our results demonstrate that implantation of the novel intracranial DES NOVA in severe ICAS is feasible, safe, and effective in selected cases, reducing the incidence of ISR, and showing excellent midterm clinical outcomes, providing a promising option for ICAS treatment.

Integration of O2-economised tumour-targeted photosensitive magnetic nanomaterials in the diagnosis and therapy of gastric cancer.

Hypoxia in the tumour microenvironment is a major limiting factor in photodynamic therapy. The present study employed a novel O2-economised photosensitizer, ACSN, to effectively curtail oxygen consumption by impeding the aerobic respiration of tumour cells, thereby increasing the reactive oxygen species (ROS) production in photodynamic therapy. To enhance the efficacy of photodynamic therapy, the active targeting peptide iRGD was employed to facilitate drug accumulation in the tumour tissue. Therefore, we constructed a targeted drug platform, ACSN/Fe3O4@MSNs-iRGD, that integrates diagnosis and treatment. The drug exhibited excellent active targeting ability towards gastric cancer MGC-803 cells and can efficiently penetrate the mitochondria upon cellular internalisation. The photosensitizer ACSN, released from the drug, effectively suppressed mitochondrial aerobic respiration to conserve oxygen and exhibited robust ROS production upon laser excitation. The core-shell structure comprises Fe3O4, which offers excellent T2 dark contrast for real-time tumour monitoring through MRI imaging. By incorporating excellent photodynamic therapy and MRI imaging capabilities, this drug can serve as an effective platform for the integration of tumour diagnosis and treatment, thus addressing the limitations associated with conventional tumour therapies. It is anticipated that this approach will soon be clinically translated.

Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression.

The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and the resulting immunosuppressive microenvironment, leading to the chronicity and recurrence of IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO2@Ce6@Van (BMCV). The BMCV exhibits precise targeting and adhesion to the S. aureus biofilm-infected region, coupled with its capacity to catalyze oxygen generation from H2O2 in the hypoxic and acidic biofilm microenvironment (BME), promoting oxygen-dependent photodynamic therapy efficacy while ensuring continuous release of manganese ions. Notably, targeted BMCV can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting the biofilm structure and impairing its barrier function, making it vulnerable to infiltration and elimination by the immune system. Furthermore, light-induced reactive oxygen species (ROS) around the biofilm can lyse S. aureus, triggering bacterium-like immunogenic cell death (ICD), releasing abundant immune costimulatory factors, facilitating the recognition and maturation of antigen-presenting cells (APCs), and activating adaptive immunity. Additionally, manganese ions in the BME act as immunoadjuvants, further amplifying macrophage-mediated innate and adaptive immune responses and reversing the immunologically cold BME to an immunologically hot BME. We prove that our synthesized BMCV elicits a robust adaptive immune response in vivo, effectively clearing primary IAIs and inducing long-term immune memory to prevent recurrence. Our study introduces a potent light-induced immunomodulatory nanoplatform capable of reversing the biofilm-induced immunosuppressive microenvironment and disrupting biofilm-mediated protective barriers, offering a promising immunotherapeutic strategy for addressing challenging S. aureus IAIs.

Gold Nanocage-Based Multifunctional Nanosensitizers for Programmed Photothermal /Radiation/Chemical Coordinated Therapy Guided by FL/MR/PA Multimodal Imaging.

Background: Radiotherapy is one of the main clinical methods for the treatment of malignant tumors at present. However, its application is limited by the radiation resistance of some tumor cells and the irradiation damage to the surrounding normal tissues, and the limitation of radiotherapy dose also affects the therapeutic effect. Therefore, developing diagnostic and therapeutic agents with imaging and radiosensitizing functions is urgently needed to improve the accuracy and efficacy of radiotherapy. Materials and Strategy: Herein, we synthesized multifunctional nanotheranostic FRNPs nanoparticles based on gold nanocages (GNCs) and MnO2 for magnetic resonance (MR)/photoacoustic (PA) imaging and combined photothermal, radiosensitive and chemical therapy. A programmed therapy strategy based on FRNPs is proposed. First, photothermal therapy is applied to ablate large tumors and increase the sensitivity of the tumor tissue to radiotherapy, then X-ray radiation is performed to further reduce the tumor size, and finally chemotherapeutic agents are used to eliminate smaller residual tumors and distant metastases. Results: As revealed by fluorescence, MR and PA imaging, FRNPs achieved efficient aggregation and retention at tumor sites of mice after intravenous injection. In vivo studies have shown that the programmed treatment of FRNPs-injected nude mice which were exposed to X-ray after 808 laser irradiation achieved the greatest inhibition of tumor growth compared with other treatment groups. Moreover, no obvious systemic toxicity was observed in all groups of mice, indicating the good biocompatibility of FRNPs and the safety of the treatment scheme. Conclusion: To sum up, our work not only showed a new radiosensitizer, but also provided a promising theranostic strategy for cancer treatment.

An Adaptable Nanoprobe Integrated with Quantitative T1 -Mapping MRI for Accurate Differential Diagnosis of Multidrug-Resistant Lung Cancer.

Multidrug resistance (MDR) is one of the major factors causing failure of non-small-cell lung cancer (NSCLC) chemotherapy. Real-time and accurate differentiation between drug-resistant and sensitive NSCLC is of primary importance for guiding the subsequent treatments and improving the therapeutic outcome. However, there is no effective method to provide such an accurate differentiation. This study creates an innovative strategy of integrating H2 O2 -responsive nanoprobes with the quantitative T1 -mapping magnetic resonance imaging (MRI) technique to achieve an accurate differential diagnosis between drug-resistant and sensitive NSCLC in light of differences in H2 O2 content in the tumor microenvironment (TME). The result demonstrates that the synthesized MIL-53(Fe)@MnO2 nanocomposites possess an excellent capability of shortening the cancer longitudinal relaxation time (T1 ) when meeting H2 O2 in TME. T1 -mapping MRI could sensitively detect this T1 variation (about 2.6-fold that of T1-weighted imaging (T1 WI)) to accurately differentiate the H2 O2 content between drug-resistant and sensitive NSCLC. In addition, the quantitative data provided by the T1 -mapping MRI dedicates correct comparison across imaging tests and is more reliable than T1 WI, thus giving it a chance for precise assessment of the anti-cancer effect. This innovative strategy of merging TME adaptable nanoprobes with the quantitative MRI technique provides a new approach for the precise diagnosis of multidrug-resistant NSCLC.

Potential use of high-resolution T2-weighted MRI with histopathologic findings in staging esophageal cancer.

Background: Magnetic resonance imaging (MRI) has shown promising capabilities in diagnosing local esophageal carcinoma. This study investigated the clinical value of high resolution (HR; small field of view and continuous thin section) axial T2-weighted MRI (HR-T2WI) as a noninvasive method for esophageal carcinoma tumor staging (T staging). Methods: Forty-two patients with biopsy-proven esophageal cancer were investigated using HR-T2WI. The discrepancies between the esophageal wall layers and tumor tissue were assessed for MRI T staging using a visual MRI signal intensity scale (low, intermediate, and high intensities). The computed tomography (CT) and MRI T staging was compared with whole-mount histopathological sections in all patients who underwent resection. Results: HR-T2WI provided a thorough view of the esophageal wall and the tumor's anatomic layers. Of the 42 patients with histological tumors (HTs), there were 6 cases with tumors classified as HT-1a, 5 cases with HT-1b, 14 cases with HT-2, and 17 cases with HT-3/4, and their MRI T stages were 5 MRI-T1a, 6 MRI-T1b, 14 MRI-T2, and 17 MRI-T3/4, respectively. After analyzing the imaging presentation at different HT staginess, we found that HR-T2WI enabled a more accurate classification than was possible with CT. The difference in accuracy between CT and T2WI was statistically significant (P<0.05) in the entire sample and in HT1-2 tumors and HT3-4 tumors. Conclusions: HR-T2WI clearly identified normal esophageal wall layers; it had high diagnostic accuracy when evaluating tumor invasion and in MRI-T staging for esophageal carcinoma. This study established staging criteria of esophageal carcinoma using HR-T2WI and indicated that this approach could be used as a supplemental noninvasive method for the local T staging of esophageal carcinoma.

Biomimetic Molybdenum Sulfide-Catalyzed Tumor Ferroptosis and Bioimaging.

The chemical generation of singlet oxygen (1 O2 ) by the MoO4 2- -catalyzed disproportionation of hydrogen peroxide (H2 O2 ) has been widely applied in numerous catalytic processes; however, such molybdate ions cannot be administered for redox-based cancer therapeutics. This work reports the albumin-mediated biomimetic synthesis of highly active molybdenum sulfide (denoted MoB) nanocatalysts that mediate the simultaneous generation of 1 O2 and superoxide anion (O2 •- ) from H2 O2 , which is relatively abundant in malignant tumors. The MoB-catalyzed reactive oxygen species (ROS) are able to activate the ferroptosis pathway and cause lipid peroxidation for efficient cancer therapy. Furthermore, for the first time, the catalytic activity of MoB is visualized in situ. Moreover, a catalytic imaging modality based on MoB is developed for specific imaging of inflammation diseases without background interference. Therefore, this study presents a biomimetic strategy toward Mo-based nanocatalysts for ROS-facilitated tumor ferroptosis and catalytic imaging.

Advances in cerebral perfusion imaging techniques in acute ischemic stroke.

The application of cerebral perfusion imaging has demonstrated significant assessment benefits and an ability to establish an appropriate triage of patients with acute ischemic stroke (AIS) and large artery occlusion (LAO) in the extended time window. Computed tomography perfusion (CTP) and magnetic resonance imaging (MRI) are routinely used to determine the ischemic core, as well as the tissue at risk, to aid in therapeutic decision-making. However, the time required to transport patients to imaging extends the door-to-reperfusion time. C-arm cone-beam CT (CBCT) is a novel tomography technology that combines 2D radiography and 3D CT imaging based on the digital subtraction angiography platform. In comparison with CT or MRI perfusion techniques, CBCT combined with catheterized angiogram or therapy can serve as a "one-stop-shop" for the diagnosis and treatment of AIS, and greatly reduce the door to reperfusion time. Here, we review the current evidence on the efficacy and theoretical basis of CBCT, as well as other perfusion techniques, with the purpose to assist clinicians to establish an effective and repaid workflow for patients with AIS and LAO in clinical practice.

Network-Based Pharmacological Study on the Mechanism of Guishao-Liujun Decoction in the Treatment of Gastric Cancer.

Objective: The aim of the study was to use a network pharmacological method to examine the mechanism of Guishao-Liujun decoction against gastric cancer (GC). Methods: The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) were used to obtain the chemical composition and targets of all the drugs of Guishao-Liujun decoction, and the targets of GC were screened using GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The obtained targets were imported into Cytoscape 3.7.2 software by using the R language to take the intersection for a Venn analysis to construct active ingredient target networks, and they were imported into the STRING database to construct protein-protein interaction (PPI) networks, with the BisoGenet plugin in Cytoscape 3.7.2 being used for analyzing network topology. On the potential target of Guishao-Liujun decoction for GC, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R-language bioconductor platform, and the outcomes were imported into Cytoscape 3.7.2 software to obtain the KEGG network map. The core targets were docked with the active components by the macromolecular docking software application AutoDock Vina. Results: A total of 243 chemical components and 1,448 disease targets including 127 intersecting targets were discovered. AKT1, TP53, and GO functional analysis were mainly associated with ubiquitination and oxidase reduction activity. In GC treatment, the KEGG analysis revealed that Guishao-Liujun decoction mainly acted through the tumor necrosis factor (TNF), interleukin 17 (IL-17), and cancer-related signaling pathways, with the best binding performance with TP53, as indicated by the outcomes of macromolecular docking. Conclusion: In the treatment of GC, Guishao-Liujun decoction works with a variety of components and targets, establishing the groundwork for further research into its mechanism of action.

Development and validation of a novel model incorporating MRI-based radiomics signature with clinical biomarkers for distinguishing pancreatic carcinoma from mass-forming chronic pancreatitis.

PURPOSE: It is difficult to make a clear differential diagnosis of pancreatic carcinoma (PC) and mass-forming chronic pancreatitis (MFCP) via conventional examinations. We aimed to develop a novel model incorporating an MRI-based radiomics signature with clinical biomarkers for distinguishing the two lesions. METHODS: A total of 102 patients were retrospectively enrolled and randomly divided into the training and validation cohorts. Radiomics features were extracted from four different sequences. Individual imaging modality radiomics signature, multiparametric MRI (mp-MRI) radiomics signature, and a final mixed model based on mp-MRI and clinically independent risk factors were established to discriminate between PC and MFCP. The diagnostic performance of each model and model discrimination were assessed in both the training and validation cohorts. RESULTS: ADC had the best predictive performance among the four individual radiomics models, but there were no significant differences between the pairs of models (all p > 0.05). Six potential radiomics features were finally selected from the 960 texture features to formulate the radiomics score (rad-score) of the mp-MRI model. In addition, the boxplot results of the distributions of rad-scores identified the rad-score as an independent predictive factor for the differentiation of PC and MFCP (p< 0.001). Notably, the nomogram integrating rad-score and clinically independent risk factors had a better diagnostic performance than the mp-MRI and clinical models. These results were further confirmed by the validation group. CONCLUSION: The mixed model was developed and preliminarily validated to distinguish PC from MFCP, which may benefit the formulation of treatment strategies and nonsurgical procedures.

Diagnostic Performance of MRA for UnrupturedAneurysms at the Distal ICA.

PURPOSE: Unruptured intracranial aneurysms (UIAs) at the distal internal carotid artery (ICA) (segments C5-C7) are difficult to accurately display on computed tomography angiography (CTA) due to the influences of bone structures and vessel curvature. We investigated the utility of three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) at 3.0­T for the detection of morphologic features compared to digital subtraction angiography (DSA). METHODS: This retrospective study included 2398 patients between January 2015 and May 2020 who underwent 3D-TOF-MRA and DSA within 3 months. Morphologic features including aneurysm size, neck width, shape and relation to adjacent arteries and other diagnostic parameters were recorded. Three observers blinded to the clinical and DSA results independently analyzed MRA data sets. The statistical difference of each aneurysm-specific variable was performed using χ2-tests and multivariate logistic regression analysis. RESULTS: A total of 551 aneurysms in 514 patients were confirmed at the distal ICA by DSA. Patient-based, aneurysm-based and location-based evaluations with 3D-TOF-MRA yielded high diagnostic accuracy in the detection of target UIAs. The accuracy of displayed morphologic features was 94.9% for size, 97.2% for neck width, 92.6% for shape, and 96.4% for relationship to adjacent vessels. Multivariate logistic regression showed that tiny (P < 0.001) or giant (P = 0.039) size and a lobulated shape (P = 0.006) significantly affected the morphologic assessment on 3D-TOF-MRA. CONCLUSION: Three-dimensional TOF-MRA can accurately depict and display morphologic features of distal ICA UIAs. Tiny or giant-sized distal ICA aneurysms and with lobulation tend to carry a great risk of misdiagnosis in morphologic assessments.

Sequence-Activated Fluorescent Nanotheranostics for Real-Time Profiling Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), as one of the most malignant tumors with dense desmoplastic stroma, forms a specific matrix barrier to hinder effective diagnosis and therapy. To date, a paramount challenge is in the search for intelligent nanotheranostics for such hypopermeable tumors, especially in breaking the PDAC-specific physical barrier. The unpredictable in vivo behaviors of nanotheranostics, that is, real-time tracking where, when, and how they cross the physical barriers and are taken up by tumor cells, are the major bottleneck. Herein, we elaborately design sequence-activated nanotheranostic TCM-U11&Cy@P with dual-channel near-infrared fluorescence outputs for monitoring in vivo behaviors in a sequential fashion. This nanotheranostic with a programmable targeting capability effectively breaks through the PDAC barriers. Ultimately, the released aggregation-induced emission (AIE) particle TCM-U11 directly interacts with PDAC cells and penetrates into the deep tissue. Impressively, this fluorescent nanotheranostic intraoperatively can map human clinical PDAC specimens with high resolution. We believe that this unique sequence-activated fluorescent strategy expands the repertoire of nanotheranostics in the treatment of hypopermeable tumors.

Molecular immuno-imaging improves tumor detection in head and neck cancer.

Detection and accurate delineation of tumor is important for the management of head and neck squamous cell carcinoma (HNSCC) but is challenging with current imaging techniques. In this study, we evaluated whether molecular immuno-imaging targeting myeloperoxidase (MPO) activity, an oxidative enzyme secreted by many myeloid innate immune cells, would be superior in detecting tumor extent compared to conventional contrast agent (DTPA-Gd) in a carcinogen-induced immunocompetent HNSCC murine model and corroborated in human surgical specimens. In C57BL/6 mice given 4-nitroquinoline-N-oxide (4-NQO), there was increased MPO activity in the head and neck region as detected by luminol bioluminescence compared to that of the control group. On magnetic resonance imaging, the mean enhancing volume detected by the MPO-targeting agent (MPO-Gd) was higher than that by the conventional agent DTPA-Gd. The tumor volume detected by MPO-Gd strongly correlated with tumor size on histology, and higher MPO-Gd signal corresponded to larger tumor size found by imaging and histology. On the contrary, the tumor volume detected by DTPA-Gd did not correlate as well with tumor size on histology. Importantly, MPO-Gd imaging detected areas not visualized with DTPA-Gd imaging that were confirmed histopathologically to represent early tumor. In human specimens, MPO was similarly associated with tumors, especially at the tumor margins. Thus, molecular immuno-imaging targeting MPO not only detects oxidative immune response in HNSCC, but can better detect and delineate tumor extent than nonselective imaging agents. Thus, our findings revealed that MPO imaging could improve tumor resection as well as be a useful imaging biomarker for tumor progression, and potentially improve clinical management of HNSCC once translated.

Effect of EAP Psychological Intervention on Improving the Mental Health of Medical Workers Under the Novel Coronavirus Epidemic in China.

Background: Due to the novel coronavirus epidemic, medical workers are under immense psychological pressure. As such, the East Campus of Shanghai Sixth People's Hospital actively adopted the Symptoms Checklist 90 (SCL-90) to evaluate the mental health of hospital staff before and after the psychological intervention from the Employee Assistance Program (EAP). Methods: Medical workers from the East Campus of Shanghai Sixth People's Hospital were recruited for this study. Psychological evaluations were conducted using the SCL-90, with a score of >160 regarded as a positive result, or in other words, an indication of abnormal psychological symptoms. The EAP adopted different forms of psychological interventions for healthcare professionals, and participation in these measures was entirely voluntary. Medical workers completed the SCL-90 again after participating in the psychological intervention, and we analyzed the changes between their two assessments. Results: Of the 1,198 total medical staff present at the hospital, 844 participated in the initial survey, while only 652 completed the survey a second time (i.e., post-psychological intervention). Multivariate logistic regression analysis found that the psychological status of hospital staff was correlated with gender, education background, and fertility status (P < 0.05). The results showed that, compared with women, men's mental health status was better, with an OR value of 0.598 (0.372-0.962). Groups with high school, junior high school, and below education levels were at higher risk of psychological problems, with OR values of 23.655 (2.815-198.784) and 9.09 (2.601-31.801), respectively. Administrative occupations and having two or more children were protective factors for mental health, and the OR values were 0.400 (0.175-0.912) and 0.327 (0.152-0.703), respectively. Following the psychological intervention, we found that the mental health of hospital workers improved, as indicated by their second SCL-90 evaluations, although the proportion of medical staff willing to participate in the second evaluation was lower than the initial assessment. There were differences in the SCL-90 scores among different occupations, and there were also differences in the scores of employees of different occupations who had participated in the two evaluations. The employees of different positions who participated in the two evaluations were matched and analyzed and found that the depression and anxiety of the doctor group were significantly reduced. In the nursing group, the total score, somatization, interpersonal sensitivity, depression, and anxiety were significantly reduced. In the medical technician group, depression, anxiety, and paranoia were reduced considerably. Among office staff, no significant differences were found. Among workers, the total score, depression, and anxiety were significantly reduced. Conclusion: Hospitals have the potential to alleviate and reduce the psychological pressure placed on medical staff members through the EAP, which can actively adopt intervention and guidance measures. The findings of this study have important implications, as reducing abnormal psychological symptoms of healthcare professionals can be helpful in the fight against the coronavirus epidemic.

SR-A-Targeted Nanoplatform for Sequential Photothermal/Photodynamic Ablation of Activated Macrophages to Alleviate Atherosclerosis.

Cardiovascular and cerebrovascular diseases induced by atherosclerosis (AS) have become the dominant cause of disability and mortality throughout the world. The typical early pathological process of AS involves the activation of inflammatory macrophages in the vulnerable plaque. In this work, we first employed chitosan-coated carbon nanocages (CS-CNCs) as nanocarriers to load Chlorin e6 (Ce6) and then linked dextran sulfate (DS) to the outermost layer by electrostatic adsorption to create a multifunctional therapeutic nanoplatform, CS-CNCs@Ce6/DS. The DS of the nanoplatform can recognize and bind to the type A scavenger receptor (SR-A), which is expressed only on the activated macrophages of the arterial plaque, so the proposed nanoplatform selectively targets these macrophages and accumulates there. Furthermore, DS can competitively inhibit cellular endocytosis of oxidized low-density lipoproteins via blocking of SR-A. The rapid photothermal conversion capability of CS-CNCs enables efficient therapeutic delivery during photothermal therapy (PTT). Interestingly, near-infrared-accelerated drug release induced by initial 808-nm laser irradiation was observed, thus enhancing the Ce6 concentration in the atherosclerotic plaque area and the efficiency of photodynamic therapy (PDT). Sequential photothermal/photodynamic ablation of the activated macrophages reduced pro-inflammatory cytokine secretion and alleviated the proliferation and migration of smooth muscle cells. These finally resulted in the stabilization and shrinkage of atherosclerotic plaques, further inhibiting the development and exacerbation of AS. Therefore, this work achieved a "1 + 1 greater than 2" effect by providing a novel approach to the treatment of atherosclerotic plaques, which is promising for the prevention of AS-related diseases.

Combined with interventional therapy, immunotherapy can create a new outlook for tumor treatment.

Recent progress in immunotherapy provides hope of a complete cure to cancer patients. However, recent studies have reported that only a limited number of cancer patients with a specific immune status, known as "cold tumor", can benefit from a single immune agent. Although the combination of immune agents with different mechanisms can partially increase the low response rate and improve efficacy, it can also result in more side effects. Therefore, discovering therapies that can improve tumors' response rate to immunotherapy without increasing toxicity for patients is urgently needed. Tumor interventional therapy is promising. It mainly includes transcatheter arterial chemoembolization, ablation, radioactive particle internal irradiation, and photodynamic interventional therapy based on a luminal stent. Interventional therapy can directly kill tumor cells by targeted drug delivery in situ, thus reducing drug dosage and systemic toxicity like cytokine release syndrome. More importantly, interventional therapy can regulate the immune system through numerous mechanisms, making it a suitable choice for immunotherapy to combine with. In this review, we provide a brief description of immunotherapies (and their side effects) on tumors of different immune types and preliminarily elaborate on interventional therapy mechanisms to improve immune efficacy. We also discuss the progress and challenges of the combination of interventional therapy and immunotherapy.

Multistage signal-interactive nanoparticles improve tumor targeting through efficient nanoparticle-cell communications.

Communication between biological components is critical for homeostasis maintenance among the convergence of complicated bio-signals. For therapeutic nanoparticles (NPs), the general lack of effective communication mechanisms with the external cellular environment causes loss of homeostasis, resulting in deprived autonomy, severe macrophage-mediated clearance, and limited tumor accumulation. Here, we develop a multistage signal-interactive system on porous silicon particles through integrating the Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide into a hierarchical chimeric signaling interface with "don't eat me" and "eat me" signals. This biochemical transceiver can act as both the signal receiver for amantadine to achieve NP transformation and signal conversion as well as the signal source to present different signals sequentially by reversible self-mimicking. Compared with the non-interactive controls, these signal-interactive NPs loaded with AS1411 and tanespimycin (17-AAG) as anticancer drugs improve tumor targeting 2.8-fold and tumor suppression 6.5-fold and showed only 51% accumulation in the liver with restricted hepatic injury.

Manganese/iron-based nanoprobes for photodynamic/chemotherapy combination therapy of tumor guided by multimodal imaging.

Early diagnosis of tumors is crucial in selecting appropriate treatment options to achieve the desired therapeutic effect, but it is difficult to accurately diagnose cancer by a single imaging modality due to technical constraints. Therefore, we synthesized a type of Fe3O4 nanoparticle with manganese dioxide grown on the surface and then prepared it by loading photosensitive drugs and traditional Chinese medicine monomers to create an integrated diagnosis/treatment multifunctional nanoplatform: Fe3O4@MnO2-celastrol (CSL)/Ce6. This nanoplatform can have full advantage of the tumor microenvironment (TME) characteristics of hypoxia (hypoxia), acidic pH (acidosis), and increased levels of reactive oxygen species (e.g., H2O2), even outside the TME. Specific imaging and drug release can also enhance tumor therapy by adjusting the hypoxic state of the TME to achieve the combined effect of chemotherapy (CT) and photodynamic therapy (PDT). Moreover, the obtained Fe3O4@MnO2-CSL/Ce6 has H2O2- and pH-sensitive biodegradation and can release the anticancer drug celastrol (CSL) and photosensitizer Ce6 in TME and simultaneously generate O2 and Mn2+. Therefore, the "dual response" synergistic strategy also confers specific drug release on nanomaterials, relieves tumor hypoxia and antioxidant capacity, and achieves significant optimization of CT and PDT. Furthermore, the resulting Mn2+ ions and Fe3O4 nanoparticles can be used for T1/T2 magnetic resonance imaging on tumor-bearing mice, and the released Ce6 can simultaneously provide fluorescence imaging functions. Therefore, Fe3O4@MnO2-CSL/Ce6 realized the synergistic treatment of PDT and CT under multimodal near-infrared fluorescence/photoacoustic (photoacoustic) imaging monitoring, showing its great potential in the accurate medical treatment of tumors.

Neutrophil-like Cell-Membrane-Coated Nanozyme Therapy for Ischemic Brain Damage and Long-Term Neurological Functional Recovery.

Oxidative stress and a series of excessive inflammatory responses are major obstacles for neurological functional recovery after ischemic stroke. Effective noninvasive anti-inflammatory therapies are urgently needed. However, unsatisfactory therapeutic efficacy of current drugs and inadequate drug delivery to the damaged brain are major problems. Nanozymes with robust anti-inflammatory and antioxidative stress properties possess therapeutic possibility for ischemic stroke. However, insufficiency of nanozyme accumulation in the ischemic brain by noninvasive administration hindered their application. Herein, we report a neutrophil-like cell-membrane-coated mesoporous Prussian blue nanozyme (MPBzyme@NCM) to realize noninvasive active-targeting therapy for ischemic stroke by improving the delivery of a nanozyme to the damaged brain based on the innate connection between inflamed brain microvascular endothelial cells and neutrophils after stroke. The long-term in vivo therapeutic efficacy of MPBzyme@NCM for ischemic stroke was illustrated in detail after being delivered into the damaged brain and uptake by microglia. Moreover, the detailed mechanism of ischemic stroke therapy via MPBzyme@NCM uptake by microglia was further studied, including microglia polarization toward M2, reduced recruitment of neutrophils, decreased apoptosis of neurons, and proliferation of neural stem cells, neuronal precursors, and neurons. This strategy may provide an applicative perspective for nanozyme therapy in brain diseases.

Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer.

BACKGROUND: Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. RESULTS: The particle size of the micelles was 42 nm, the zeta potential increased from - 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. CONCLUSIONS: This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.