Platelets play a critical role in tumor development, metastasis and chemoresistance, making the effective killing of tumor cells and simultaneously targeted disruption of platelet functions essential for improving cancer treatment outcomes, especially in post-surgical malignant tumor patients. Here, we develop soft hybrid microparticles (3D-PMPs) by fusing tumor-repopulating cell-derived microparticles with inactivated platelet membranes to deliver the anticancer agent doxorubicin (DOX@3D-PMPs). Leveraging their unique softness, DOX@3D-PMPs demonstrate superior tumor accumulation, deep tumor penetration, and enhanced internalization into tumor cells, leading to efficient tumor cell killing. Additionally, 3D-PMPs function as highly targeted platelet decoys to disrupt platelet-tumor cell interaction and reduce platelet-driven tumor proliferation and metastasis. Mechanistically, Toll-like receptor 4 (TLR-4) presented on 3D-PMPs is responsible for their platelet decoy function. DOX@3D-PMPs demonstrate significantly enhanced therapeutic efficacy in both orthotopic 4T1 breast tumors and post-surgical orthotopic 4T1 breast tumors. This work offers a novel and effective approach to enhance the therapeutic outcomes in cancer treatment, particularly in post-surgical settings.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the abnormal aggregation of α-synuclein (α-Syn), involving complex regulatory networks where the roles and mechanisms of circular RNAs (circRNAs) remain underexplored. Through RNA sequencing analysis, we identified significant upregulation of circ_0005654 (derived from the PRDM5 gene) in PD patients. Functional studies demonstrated that circ_0005654 overexpression promotes α-Syn accumulation through a dual regulatory mechanism: (1) direct enhancement of its transcriptional/translational activation of α-Syn and (2) indirect suppression of autophagic clearance via miR-588 sequestration-mediated inhibition of the p62-dependent autophagy pathway. Specifically, circ_0005654 functions as a molecular sponge for miR-588, thereby coordinately enhancing α-Syn synthesis while impairing its degradation. This study not only establishes the functional role of circRNAs in PD pathogenesis but also elucidates circ_0005654 as a promising therapeutic candidate for targeted modulation of α-Syn aggregation.

OBJECTIVE:Exploring the role and mechanism of a novel bioorthogonal system using transition metals as catalysts in the treatment of hepatocellular carcinoma (HCC). METHODS:Initially, a catalytic ruthenium (Ru) complex and the substrate alloc-RH 110 were synthesized, followed by the identification of their structures utilizing mass spectrometry and nuclear magnetic resonance (NMR) techniques. The catalytic efficacy of the Ru complex was then assessed using a fluorescence spectrophotometer. Subsequently, employing HepG2 cells as the cellular source, cell-derived vesicles encapsulating the Ru complexes, designated as EVs@Ru, were prepared. The EVs@Ru were characterized by measuring their particle size and Zeta potential, observing morphological features under transmission electron microscopy (TEM), and detecting specific protein expressions via Western blot analysis. Drug loading within the EVs@Ru was quantified using inductively coupled plasma mass spectrometry (ICP-MS), and their catalytic efficiency was evaluated. In vitro, the low-activity prodrug alloc-DOX was synthesized and its toxicity, along with the drug concentration in EVs@Ru, was determined. Further, the catalytic cytotoxicity of alloc-DOX against HepG2 cells encapsulated in EVs@Ru was analyzed through microscopic observation, CCK-8 assays, and apoptosis experiments. For in vivo studies, a tumor-bearing mouse model was established using human liver cancer HepG2 cells to observe the antitumor effects. Finally, the primary organs of each group of tumor-bearing mice were assessed for in vivo safety. RESULTS:ESI-MS and 1H NMR confirmed the accurate structure of Ru complexes and alloc-RH 110. The Ru complexes achieved full catalytic conversion of alloc-RH 110 within 24 hours. EVs and EVs@Ru exhibited particle sizes of ∼116.85 nm and ∼281.88 nm, respectively, with Zeta potentials of ∼-20.86 mV and ∼-25.89 mV, both appearing quasi-circular under TEM. WB analysis verified the presence of vesicle-specific marker proteins in both, confirming their cell-derived nature. ICP-MS determined a drug loading of 21.90 μg/mL for EVs@Ru, with an encapsulation efficiency of ∼24.86%. Fluorescence spectrophotometry demonstrated 100% catalytic efficiency for EVs@Ru. Synthetic alloc-DOX validated by 1H NMR and ESI-MS matched literature data. MTT and CCK-8 assays confirmed low toxicity for alloc-DOX and Ru complexes, setting the experimental drug concentration at 4μM. In vitro, the EVs@Ru+alloc-DOX group exhibited potent HepG2 cell killing and apoptosis. In vivo, this group significantly inhibited tumor growth in tumor-bearing mice, with no observed toxicity to vital organs, indicating good biosafety. CONCLUSION:The integration of bio-derived microvesicles (MVs) with transition metal catalysts has resulted in a biologically orthogonal system for efficient Ru complex delivery to tumor sites. This system facilitates controlled release of the Ru complexes, enabling tumor cell elimination. This innovative strategy holds great promise for enhancing tumor immunity and targeted therapeutic approaches.

Recently, oncolytic virus (OV) therapy has shown great promise in treating malignancies. However, intravenous safety and inherent lack of immunity are two significant limitations in clinical practice. Herein, we successfully developed a recombinant Newcastle disease virus with porcine α1,3GT gene (NDV-GT) triggering hyperacute rejection. We demonstrated its feasibility in preclinical studies. The intravenous NDV-GT showed superior ability to eradicate tumor cells in our innovative CRISPR-mediated primary hepatocellular carcinoma monkeys. Importantly, the interventional clinical trial treating 20 patients with relapsed/refractory metastatic cancer (Chinese Clinical Trial Registry of WHO, ChiCTR2000031980) showed a high rate (90.00%) of disease control and durable responses, without serious adverse events and clinically functional neutralizing antibodies, further suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of NDV-GT for immunovirotherapy. Collectively, our results demonstrate the high safety and efficacy of intravenous NDV-GT, thus providing an innovative technology for OV therapy in oncological therapeutics and beyond.

The integration of ferroptosis induction with cancer immunotherapy has emerged as a promising approach in oncology, offering dual mechanisms to overcome therapeutic resistance and tumor heterogeneity. Nevertheless, the dynamic and complicated crosstalk between ferroptosis processes and immune regulation in tumor microenvironments presents both opportunities and challenges. By inducing lipid peroxidation in tumor tissues, ferroptotic tumor cell death can stimulate immunogenicity. Nevertheless, excessive lipid peroxidation may paradoxically impair the functionality of multiple immune cells, thereby presenting crosstalk challenges in therapeutic strategies. To address these crosstalk challenges, several advanced drug delivery strategies have been proposed, such as immunostimulatory active pharmaceutical ingredients co-delivery, tumor-targeted delivery, and stimuli-responsive delivery. These drug delivery strategies demonstrate dual therapeutic efficacy by synergistically potentiating ferroptosis induction in malignant cells while concurrently mitigating immunotoxicity and even augmenting antitumor immunity. This review offers detailed insights into the crosstalk between ferroptosis and tumor immunity, along with a guiding overview of the three delivery strategies. The current obstacles and translational potential were thoroughly analyzed, providing valuable perspectives for future research.

Although photothermal therapy (PTT) has emerged as a promising strategy for tumor treatment, the antitumor efficiency is still unsatisfactory due to incomplete tumor ablation. Therefore, we propose a tailored in situ tumor microenvironment (TME) igniting strategy that leverages tumor extracellular metabolic heterogeneity (EMH) to transform metabolites into antitumor components. In this study, polydopamine (PDA) with photothermal performance was formulated into nanoparticles with polyethylenimine. Subsequently, lipoxygenase (LOX) and catalase (CAT) were adsorbed onto the nanoparticle surface, forming the PDA@CL nanoigniter, which was further integrated into microneedle patches. Upon penetration into tumors, the nanoigniters are rapidly released and accumulate in the deep tumor sites, and considerable free fatty acids (FFAs) are generated by PTT. Under abundant H2O2, CAT decomposes H2O2 to supply O2, which efficiently helps LOX in catalyzing FFAs to promote lipid peroxide generation and induce tumor ferroptosis. Subsequently, the release of tumor-associated antigens promotes tumor-associated macrophages toward the M1 phenotype and stimulates dendritic cell maturation, thereby activating antitumor immune responses. Consequently, the proposed system established a PTT/ferroptosis/immunotherapy multimodal therapy to form a positive feedback loop of tumor-killing, demonstrating significant antitumor efficacy. Our research provides a versatile framework for leveraging EMH to enhance photothermal-mediated multimodal therapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Emerging and recurrent infectious diseases caused by human coronaviruses (HCoVs) continue to pose a significant threat to global public health security. In light of this ongoing threat, the development of a broad-spectrum drug to combat HCoVs is an urgently priority. Herein, we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). These aptamers have nanomolar affinity with the nucleocapsid protein (NP) of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also show excellent binding efficiency to the N proteins of both SARS, MERS, HCoV-OC43 and -NL63 with affinity KD values of 1.31 to 135.36 nM. Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant (BA.5) with EC50 values at 2.00 nM and 41.08 nM, respectively. The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs (−229E and -HKU1). In conclusion, we have identified six aptamers with a high pan-coronavirus antiviral activity, which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various kinds of wound dressings, such as gauze, bandages, sponges, patches, and microspheres, have been developed for wound healing. Among them, microsphere-based tissue dressings have attracted increasing attention due to the advantage of easy to fabricate, excellent physicochemical performance and superior drug release ability. In this review, we first introduced the common methods for microspheres preparation, such as emulsification-solvent method, electrospray method, microfluidic technology as well as phase separation methods. Next, we summarized the common biomaterials for the fabrication of the microspheres including natural polymers and synthetic polymers. Then, we presented the application of the various microspheres from different processing methods in wound healing and other applications. Finally, we analyzed the limitations and discussed the future development direction of microspheres in the future.

Viruses are routinely isolated from infected cells through freeze–thaw (F–T) cycles or sonication. The aim of this study was to compare different methods for efficient isolation of Newcastle disease virus (NDV) particles from BSR-T7/5 (BSR) cells. The BSR cells were infected with NDV LaSota strain, and the virus particles were isolated via F–T, sonication, sonication followed by F–T, and F–T followed by sonication. The infection and proliferation kinetics of the virus were analyzed by cytopathic observation and monitoring of hemagglutination (HA) titers. The virus isolated by sequential F–T and sonication was amplified through five passages of BSR cells, and then used to infect the HepG2 cells. The viability and apoptosis rates of the infected cells were evaluated by Cell Counting Kit-8 assay and Annexin V-FITC/PI staining respectively. We successfully obtained NDV particles from persistently infected BSR cells through all four methods, which indicated that the LaSota can effectively replicate in BSR cells. However, F–T followed by sonication was optimum in terms of separation effect. The virus particles isolated by this method still exhibited cytolytic activity against HepG2 cells. Thus, our novel method can be applied to NDV production and generation of tumor vaccines.

article: Predicting the prognosis of liver cancer patients based on cell differentiation trajectory and application of nanomaterials in treatment - Minerva Surgery 2021 Dec 10 - Minerva Medica - Journals

Hepatocellular carcinoma development and many other tumors are closely related to alpha-fetoprotein (AFP), its determination can be used as a positive test for tumors. It is mainly used clinically as a serum marker to diagnose and monitor the efficacy of primary hepatocellular carcinoma. Therefore, a variety of biosensors have been developed to detect AFP. Electrochemical sensors integrate a variety of detection methods. They have inherent advantages over other types of sensors, they are fast, portable, simple, and highly sensitive. Some meaningful electrochemical biosensors work with nanomaterials acting as signal amplification elements or as signal amplification catalysts. This review introduced the field of biosensors and discuss about the use of nanomaterials in electrochemical sensing, specificity electrochemical biosensing of AFP. The study ends with a discussion about the prospects for nanomaterial-based signal amplification and future research directions.

Background and Objective: Transition metals are commonly used catalysts in bioorthogonal chemistry and have attracted extensive attention in biochemistry because of their efficient catalytic performance. In recent years, transition metal-mediated cycloaddition reactions, bond cleavage, and formation reactions are being actively explored for tumor treatment. However, the direct application of transition metals in complex biological environments has several problems, including poor solubility, toxicity, and easy inactivation. The combination of transition metals and nanomaterials can solve those problems by playing a bioorthogonal catalytic role in tumor treatment. In this review, we summarize some research on the application of transition metals modified by nanomaterials in tumor therapy and discuss the potential and challenges of transition metal-mediated bioorthogonal therapy in comprehensive tumor therapy. Methods: English literature on transition metal in cancer treatment was searched in PubMed and Web of Science. The main search terms were "cancer treatment", "bioorthogonal reaction", "transition metal", "bioorthogonal catalysis", etc. Key Content and Findings: This review summarizes research on several major transition metals that can be used for bioorthogonal catalysis with the assistance of nanomaterials in anti-tumor therapy. In addition, bioorthogonal catalysis is a new supplement to antitumor therapy. We have compiled the potential challenges of the clinical application of transition metal-based nanocatalysts, which lays the foundation for future research related to medicinal chemistry and targeted cancer therapy. Conclusions: Most of the transition metals still have a lot of room for exploration in cancer treatment research. We still need more research to confirm the feasibility of in vivo and clinical trials.

Hydrogels with excellent flexibility, water retention, and biocompatibility are natural carriers for drug delivery. However, the poor drug compatibility seriously limits the practical application of traditional PNIPAM-based hydrogel. Herein, a photothermal regulated smart hydrogel was synthesized by introducing poly(ionic liquids) chain into the binary polymer chain. The temperature-induced hydrophilic-hydrophobic switchable poly(ionic liquids) chain endows the smart hydrogel with editable transparency, enabling intuitive visualization of drug loading and releasing capacity. The smart hydrogel could be used as NIR/temperature-controlled drug carrier to achieve efficient and visualized release (40.8 % drug release rate in 30 min). Besides, the smart hydrogel sensor showed excellent strain sensing sensitivity (gauge factor = 3.73), short response time (116 ms), high durability (1800 s at 20 % strain), and impressive temperature sensing sensitivity (TCR =-1.252 %/degrees C). Based on the excellent sensing performance and editable drug-delivery ability, the smart hydrogel was assembled into a dy-namic wound management system to realize personalized wound treatment and wireless state diagnosis. The wireless sensor early warning system could realize wireless monitoring and state warning of joints (fingers, ankles, and elbows), exhibiting guiding significance for rehabilitation treatment. Moreover, the high-resolution sensor array composed of 5 x 5 smart hydrogels could accurately identify the strain, temperature and NIR light in three-dimensional space and direction. In short, the smart hydrogel provides an innovative solution to personalized wound diagnosis and assisted rehabilitation.

Tumor markers are important substances for assessing cancer development. In recent years, RNA tumor markers have attracted significant attention, and studies have shown that their abnormal expression of post-transcriptional regulatory genes is associated with tumor progression. Therefore, RNA tumor markers are considered as potential targets in clinical diagnosis and prognosis. Many studies show that biosensors have good application prospects in the field of medical diagnosis. The application of biosensors in RNA tumor markers is developing rapidly. These sensors have the advantages of high sensitivity, excellent selectivity, and convenience. However, the detection abundance of RNA tumor markers is low. In order to improve the detection sensitivity, researchers have developed a variety of signal amplification strategies to enhance the detection signal. In this review, after a brief introduction of the sensing principles and designs of different biosensing platforms, we will summarize the latest research progress of electrochemical, photoelectrochemical, and fluorescent biosensors based on signal amplification strategies for detecting RNA tumor markers. This review provides a high sensitivity and good selectivity sensing platform for early-stage cancer research. It provides a new idea for the development of accurate, sensitive, and convenient biological analysis in the future, which can be used for the early diagnosis and monitoring of cancer and contribute to the reduction in the mortality rate.

Anlotinib is a tyrosine kinase inhibitor. It inhibits tumour growth by inhibiting the phosphorylation of angiogenesis-related receptors and attenuating the expression of related signals downstream of this pathway. Anlotinib has shown good antitumour activity and tolerability in patients with tumours, and multitargeted inhibition of angiogenesis does not lead to drug resistance due to excessive bypass activation. Moreover, its antitumour activity is superior to that of sunitinib, a conventional angiogenesis inhibitor. Results from several clinical studies have indicated that anlotinib improves progression-free survival and overall survival. Most adverse effects of anlotinib treatment were found to be alleviated by dose adjustment and symptomatic supportive therapy in several clinical trials. Therefore, anlotinib is a promising drug for oncology patients that is safe, effective, and tolerable, allowing patients with advanced cancer to benefit from drug therapy. This article reviews the basic information, antitumour mechanisms, clinical applications, clinical trial findings, and adverse effects of anlotinib and describes the problems in anlotinib research. It concludes with an outlook on future work.

Thrombin is a multifunctional serine protease that plays an important role in coagulation and anticoagulation processes. Aptamers have been widely applied in biosensors due to their high specificity, low cost and good biocompatibility. This review summarizes recent advances in thrombin quantification using aptamer-based biosensors. The primary focus is optical sensors and electrochemical sensors, along with their applications in thrombin analysis and disease diagnosis.

In recent years, nanotechnology has been widely used in the field of tumor treatment. Some nanomedicine applications have been approved for tumor treatment, but nanomedicine has not so far demonstrated the anticipated therapeutic effect. In this process, the tumor microenvironment plays a major role. The tumor microenvironment is an internal environment that supports tumor occurrence, development, and metastasis. It is composed of tumor cells and related cells, intercellular substances, capillaries, and biomolecules that pervade both the tumor mass itself and its surrounding area. The tumor microenvironment can be a potential target for tumor treatment. Therefore, nano-antitumor therapy targeting the tumor microenvironment has received widespread attention. This therapy is based on the physiological characteristics of tumors that differ from those of normal tissues. The tumor microenvironment is used as a therapeutic target, and drugs are delivered to the tumor site through nanoparticles-enabled targeting to achieve fast, controllable, and efficient tumor killing. This article reviews basic research such as design principles and applications of nano-antitumor therapeutic strategies targeting the tumor microenvironment, providing a theoretical basis and new research ideas for tumor treatment.