Qin Zhang

Bio: Qin Zhang is an academic researcher from Shandong Normal University. The author has contributed to research in topics: Chemistry & Medicine. The author has co-authored 1 publications.

Monitoring the Activation of Caspases-1/3/4 for Describing the Pyroptosis Pathways of Cancer Cells

Abstract: Pyroptosis is closely related to inhibiting the occurrence and development of tumors. However, the pyroptosis pathways (PPs) impacted by different stimulants are still unknown. To accurately understand the PP in cancer cells, we designed a multicolor fluorescent nanoprobe (Cas-NP) to monitor the activation of caspases-1/3/4 during pyroptosis. The Cas-NP was prepared by the assembly of three different fluorophores-labeled peptides, specific response to caspases-1/3/4 on Au nanoparticles via the Au-Se bond to in situ monitor caspase-1/3/4 with high selectivity and sensitivity. Moreover, the selenopeptide specific to caspase-4 (Cyanine-5-LEVD-SeH) was synthesized for the first time to overcome the difficulty in commercial synthesis. During the pyroptosis of cancer cells induced by adenosine triphosphate (ATP), only the fluorescence of caspase-1 significantly increases. When the cells are stimulated with lipopolysaccharide (LPS), the fluorescence signals corresponding to caspases-3 and 4 first appear and then the fluorescence of caspase-1 is observed. Furthermore, the inhibitor study indicates that the activated caspase-4 can lead to the activation of caspase-1 after the LPS treatment. We first discovered that caspase-3 is activated during the pyroptosis process stimulated by LPS and further verified the activation sequence of caspases-1/3/4 via visualized fluorescence detection. The study provides an effective tool for understanding complex signaling mechanisms in pyroptosis cells and new ideas to explore useful therapeutic inhibitors based on pyroptosis.

Acidic-driven aggregation of selenol-functionalized zwitterionic gold nanoparticles improves photothermal treatment efficacy of tumors

Abstract: Improving nanomedicines’ drug delivery efficiency and tumor penetration are of great significance for clinical cancer therapies. Despite smart gold nanoparticles (Au NPs) with dynamic size can effectively cope with the...

Determination of Titanium (IV) Oxide Nanoparticles Released from Textiles by Single Particle – Inductively Coupled Plasma – Mass Spectrometry (SP-ICP-MS)

Abstract: Monitoring TiO2 nanoparticles (NPs) that are released from functional textiles is significant for assessing the potential risk to consumers. However, determining the size distribution of TiO2 NPs is still a challenge due to agglomeration. The present study employed single particle–inductively coupled plasma–mass spectrometry (SP-ICP-MS) to quantify TiO2 NPs released from functional textiles. Through screening dispersants and validating the standard samples, an accurate method for determining the size and number of TiO2 NPs was developed. The validated procedure was successfully used to determine the release of TiO2 NPs from yarn in sweat and water media throughout the day. The result revealed that the yarn decorated with TiO2 NPs released approximately the same particle size distribution from 60 to 260 nm in both media. The released particle concentration was 0.094 µg/mL with a mean size of 136 nm in water and a particle concentration of 0.120 µg/mL with a mean size of 133 nm in sweat. Additionally, based upon transmission electron microscopy, anatase TiO2 NPs were identified. It is expected that this work is significant in the evaluation of the toxicological effects of multifunctional textiles modified by TiO2 NPs on human health.

Self-Assembly-Based Nanoprobes for the Simultaneous Detection and Downregulation of HSP90α mRNA to Enhance Photothermal Therapy.

Abstract: Although photothermal therapy (PTT) has been widely applied for tumor treatment, tumor cells thermotolerance still limits PTT efficiency. Since the overexpressed HSP90α in tumor cells further enhances thermotolerance and protects them from PTT damage, a new nanoprobe that can specifically detect and downregulate HSP90α mRNA was developed to enhance the PTT effect. Based on the HSP90α mRNA sequence, the nanoprobe Au-DNA1/DNA2 can specifically bind to HSP90α mRNA for recovering its fluorescence and further inhibit the synthesis of HSP90α to reduce tumor heat tolerance. Moreover, another nanoprobe, Au-DNA3, can self-assemble with the Au-DNA1 nanoprobe after the detection to form Au aggregations to enhance PTT afterward for better efficiency. Simultaneously, such a design improves tissue penetration and tumor retention, thereby reducing the damage to the surrounding normal tissues. Both in vitro and in vivo experiments showed that the nanoprobes have excellent tumor diagnosis and cancer treatment capabilities, which is of great significance for clinical translational applications.

Emerging Biomaterials Imaging Antitumor Immune Response

Abstract: Immunotherapy is one of the most promising clinical modalities for the treatment of malignant tumors and has shown excellent therapeutic outcomes in clinical settings. However, it continues to face several challenges, including long treatment cycles, high costs, immune‐related adverse events, and low response rates. Thus, it is critical to predict the response rate to immunotherapy by using imaging technology in the preoperative and intraoperative. Here, the latest advances in nanosystem‐based biomaterials used for predicting responses to immunotherapy via the imaging of immune cells and signaling molecules in the immune microenvironment are comprehensively summarized. Several imaging methods, such as fluorescence imaging, magnetic resonance imaging, positron emission tomography imaging, ultrasound imaging, and photoacoustic imaging, used in immune predictive imaging, are discussed to show the potential of nanosystems for distinguishing immunotherapy responders from nonresponders. Nanosystem‐based biomaterials aided by various imaging technologies are expected to enable the effective prediction and diagnosis in cases of tumors, inflammation, and other public diseases.

Tumor acidity/redox hierarchical-activable nanoparticles for precise combination of X-ray-induced photodynamic therapy and hypoxia-activated chemotherapy.

Abstract: With the advantages of deep tissue penetration and controllability, external X-ray-induced photodynamic therapy (X-PDT) is highly promising for combined cancer therapy. In addition to the low efficiency of photosensitizer (PS) delivery to tumor sites, however, the radiation- and drug-resistance of hypoxic cells inside the tumor after X-PDT also limit its benefits. Herein, we develop a combined therapeutic modality based on an intelligent nanosized platform (DATAT-NPVT) with tumor acidity-activated TAT presenting and redox-boosted release of tirapazamine (TPZ) for more precise and synchronous X-PDT and selective hypoxia-motivated chemotherapy. After DATAT-NPVT has accumulated in tumor tissues via decreased blood clearance by masking of the TAT ligand, its targeting ability is reactivated by tumor pH (∼6.8), which enhances tumoral cellular uptake. Upon low-dose X-ray irradiation, the encapsulated verteporfin (VP) generates reactive oxygen species (ROS) to carry out X-PDT against MDA-MB-231 breast tumors. As a result of the abundant GSH-triggered degradation of ditelluride bridged bonds, the cascaded TPZ release and activation in the hypoxic environment following X-PDT would produce highly cytotoxic radicals to serve as antitumor agents to kill the remaining hypoxic tumor cells. This concept provides new avenues for the design of hierarchical-responsive drug delivery systems and represents a proof-of-concept combinatorial tumor treatment.

NLRP3-mediated pyroptosis in diabetic nephropathy

Abstract: Diabetic nephropathy (DN) is the main cause of end-stage renal disease (ESRD), which is characterized by a series of abnormal changes such as glomerulosclerosis, podocyte loss, renal tubular atrophy and excessive deposition of extracellular matrix. Simultaneously, the occurrence of inflammatory reaction can promote the aggravation of DN-induced kidney injury. The most important processes in the canonical inflammasome pathway are inflammasome activation and membrane pore formation mediated by gasdermin family. Converging studies shows that pyroptosis can occur in renal intrinsic cells and participate in the development of DN, and its activation mechanism involves a variety of signaling pathways. Meanwhile, the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome can not only lead to the occurrence of inflammatory response, but also induce pyroptosis. In addition, a number of drugs targeting pyroptosis-associated proteins have been shown to have potential for treating DN. Consequently, the pathogenesis of pyroptosis and several possible activation pathways of NLRP3 inflammasome were reviewed, and the potential drugs used to treat pyroptosis in DN were summarized in this review. Although relevant studies are still not thorough and comprehensive, these findings still have certain reference value for the understanding, treatment and prognosis of DN.

Switch-on Fluorescence Analysis of Protease Activity with the Assistance of a Nickel Ion-Nitrilotriacetic Acid-Conjugated Magnetic Nanoparticle

Abstract: Heterogeneous protease biosensors show high sensitivity and selectivity but usually require the immobilization of peptide substrates on a solid interface. Such methods exhibit the disadvantages of complex immobilization steps and low enzymatic efficiency induced by steric hindrance. In this work, we proposed an immobilization-free strategy for protease detection with high simplicity, sensitivity and selectivity. Specifically, a single-labeled peptide with oligohistidine-tag (His-tag) was designed as the protease substrate, which can be captured by a nickel ion-nitrilotriacetic acid (Ni-NTA)-conjugated magnetic nanoparticle (MNP) through the coordination interaction between His-tag and Ni-NTA. When the peptide was digested by protease in a homogeneous solution, the signal-labeled segment was released from the substrate. The unreacted peptide substrates could be removed by Ni-NTA-MNP, and the released segments remained in solution to emit strong fluorescence. The method was used to determine protease of caspase-3 with a low detection limit (4 pg/mL). By changing the peptide sequence and signal reporters, the proposal could be used to develop novel homogeneous biosensors for the detection of other proteases.