Hydrogel in the Treatment of Traumatic Brain Injury.

The high prevalence of traumatic brain injury (TBI) poses an important global public health challenge. Current treatment modalities for TBI primarily involve pharmaceutical interventions and surgical procedures; however, the efficacy of these approaches remains limited. In the field of regenerative medicine, hydrogels have garnered significant attention and research efforts.

Developing a Rhodium(III) Complex to Reprogram the Tumor Immune and Metabolic Microenvironments: Overcoming Multidrug Resistance and Metastasis in Non-Small Cell Lung Cancer.

To effectively inhibit the growth and metastasis of non-small cell lung cancer (NSCLC) and overcome its multidrug resistance (MDR), we designed and synthesized a series of rhodium (Rh, III) 2-benzoylpyridine thiosemicarbazone complexes. Through studying their structure-activity relationships, we identified the Rh(III) complex (Rh4) with excellent cytotoxicity against multidrug-resistant lung cancer cells (A549/ADR cells). Additionally, we successfully constructed an apoferritin (AFt) nanoparticle (NP) delivery system (AFt-Rh4 NPs).

Anticancer Tetranuclear Cu(I) Complex Catalyzes a Click Reaction to Synthesize a Chemotherapeutic Agent in situ to Achieve Targeted Dual-Agent Combination Therapy for Cancer.

To develop next-generation metal-based drugs and dual-drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual-agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). We also constructed an apoferritin (AFt)-Cu4 nanoparticles (NPs) delivery system.

Developing a Palladium(II) Agent to Overcome Multidrug Resistance and Metastasis of Liver Tumor by Targeted Multiacting on Tumor Cell, Inactivating Cancer-Associated Fibroblast and Activating Immune Response.

To targeted overcome the multidrug resistance (MDR) and metastasis of liver tumors, we proposed to develop a palladium (Pd) agent based on a specific residue of human serum albumin (HSA) for multiacting on tumor cell and other components in the tumor microenvironment. To this end, a series of Pd(II) 2-acetylpyridine thiosemicarbazone compounds were optimized to obtain a Pd(II) compound (5b) with significant cytotoxicity against HepG2/ADM cells. Subsequently, we constructed a HSA-5b complex delivery system and revealed the structural mechanism of HSA delivering 5b.

Rational Design of a Hetero-multinuclear Gadolinium(III)-Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer.

For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)-Cu(II) thiosemicarbazone complex () and then constructed a @AFt nanoparticle (NP) delivery system. /@AFt NPs not only had significant T-weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy.

Developing a Copper(II) Isopropyl 2-Pyridyl Ketone Thiosemicarbazone Compound Based on the IB Subdomain of Human Serum Albumin-Indomethacin Complex: Inhibiting Tumor Growth by Remodeling the Tumor Microenvironment.

To develop a next-generation metal agent and dual-agent multitargeted combination therapy, we developed a copper (Cu) compound based on the properties of the human serum albumin (HSA)-indomethacin (IND) complex to remodel the tumor microenvironment (TME). We optimized a series of Cu(II) isopropyl 2-pyridyl ketone thiosemicarbazone compounds to obtain a Cu(II) compound (C4) with significant cytotoxicity and then constructed an HSA-IND-C4 complex (HSA-IND-C4) delivery system. IND and C4 bind to the hydrophobic cavities of the IB and IIA domains of HSA, respectively.

Designing a Mitochondria-Targeted Theranostic Cyclometalated Iridium(III) Complex: Overcoming Cisplatin Resistance and Inhibiting Tumor Metastasis through Necroptosis and Immune Response.

To develop a potential theranostic metal agent to reverse the resistance of cancer cells to cisplatin and effectively inhibit tumor growth and metastasis, we proposed to design a cyclometalated iridium (Ir) complex based on the properties of the tumor environment (TME). To the end, we designed and synthesized a series of Ir(III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes by modifying the hydrogen atom(s) of the N-3 position of 2-hydroxy-1-naphthaldehyde thiosemicarbazone compounds and the structure of cyclometalated Ir(III) dimers and then investigated their structure-activity and structure-fluorescence relationships to obtain an Ir(III) complex (Ir5) with remarkable fluorescence and cytotoxicity to cancer cells. Ir5 not only possesses mitochondria-targeted properties but also overcomes resistance and effectively inhibits tumor growth and metastasis .

Developing a Hetero-Trinuclear Erbium(III)-Copper(II) Complex Based on Apoferritin: Targeted Photoacoustic Imaging and Multimodality Therapy of Tumor.

For the integration of targeted diagnosis and treatment of tumor, we innovatively designed and synthesized a single-molecule hetero-multinuclear Er(III)-Cu(II) complex () and then constructed an @apoferritin (AFt) nanoparticle (NP) delivery system. and @AFt NPs not only provided an evident photoacoustic imaging (PAI) signal of the tumor but also effectively inhibited tumor growth by integrating photothermal therapy, chemotherapy, and immunotherapy. @AFt NPs improved the targeting ability and decreased the systemic toxicity of .

Novel mono-, bi-, tri- and tetra-nuclear copper complexes that inhibit tumor growth through apoptosis and anti-angiogenesis.

To develop the next-generation metal agents for efficiently inhibiting tumor growth, a series of novel mononuclear, binuclear and trinuclear copper (Cu) thiophene-2-formaldehyde thiosemicarbazone complexes and a tetranuclear Cu 1,2,4-triazole-derived complex have been synthesized and their structure-activity relationships have been studied. The trinucleated Cu complex showed the strongest inhibitory activity against T24 cells among all the Cu complexes. Its antitumor effect in vivo was superior to that of cisplatin, with reduced side effects.

Developing a Ruthenium(III) Complex to Trigger Gasdermin E-Mediated Pyroptosis and an Immune Response Based on Decitabine and Liposomes: Targeting Inhibition of Gastric Tumor Growth and Metastasis.

To develop next-generation metal drugs with high efficiency and low toxicity for targeting inhibition of gastric tumor growth and metastasis, we not only optimized a series of ruthenium (Ru, III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes to obtain a Ru(III) complex () with remarkable cytotoxicity but also constructed a -decitabine (DCT)/liposome (Lip) delivery system (-DCT-Lip). The results showed that -DCT-Lip not only had a stronger capacity to inhibit gastric tumor growth and metastasis than -DCT but also addressed the co-delivery problems of -DCT and improved their targeting ability. Furthermore, we confirmed the mechanism of -DCT/-DCT-Lip inhibiting the growth and metastasis of a gastric tumor.

Developing a Multitargeted Anticancer Palladium(II) Agent Based on the His-242 Residue in the IIA Subdomain of Human Serum Albumin.

To obtain next-generation metal drugs that can overcome the deficiencies of platinum (Pt) drugs and treat cancer more effectively, we proposed to develop a multitargeted palladium (Pd) agent to the tumor microenvironment (TME) based on the specific residue(s) of human serum albumin (HSA). To this end, we optimized a series of Pd(II) 2-benzoylpyridine thiosemicarbazone compounds to obtain a Pd agent (5b) with significant cytotoxicity. The HSA-5b complex structure revealed that 5b bound to the hydrophobic cavity in the HSA IIA subdomain and then His-242 replaced a leaving group (Cl) of 5b, coordinating with the Pd center.

Developing a Gadolinium(III) Compound Based on Apoferritin for Targeted Magnetic Resonance Imaging and Dual-Modal Therapy of Cancer.

To integrate targeted diagnosis and treatment of cancer, we proposed to develop a gadolinium (Gd) agent based on the properties of apoferritin (AFt). To this end, we not only optimized a series of Gd(III) 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazone compounds to obtain a Gd(III) compound (C4) with remarkable -weighted magnetic resonance imaging (MRI) performance and cytotoxicity to cancer cells but also constructed an AFt-C4 nanoparticle (NP) delivery system. Importantly, AFt-C4 NPs improved the targeting ability of C4 and showed enhanced MRI performance and tumor growth inhibition ratio relative to C4 alone.

Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin.

To develop the next-generation Pt drug with remarkable activity and low toxicity to maximally inhibit tumor growth, we optimized a Pt(II) thiosemicarbazone compound (C4) with remarkable cytotoxicity to SK-N-MC cells and then constructed a new human serum albumin-C4 (HSA-C4) complex delivery system. The results showed that C4 and the HSA-C4 complex have remarkable therapeutic efficiency and almost no toxicity; they induced apoptosis and inhibited tumor angiogenesis. This system showed potential as a practical Pt drug.

A Hashing-Based Framework for Enhancing Cluster Delineation of High-Dimensional Single-Cell Profiles.

Unlabelled: Although many methods have been developed to explore the function of cells by clustering high-dimensional (HD) single-cell omics data, the inconspicuously differential expressions of biomarkers of proteins or genes across all cells disturb the cell cluster delineation and downstream analysis. Here, we introduce a hashing-based framework to improve the delineation of cell clusters, which is based on the hypothesis that one variable with no significant differences can be decomposed into more diversely latent variables to distinguish cells. By projecting the original data into a sparse HD space, fly and densefly hashing preprocessing retain the local structure of data, and improve the cluster delineation of existing clustering methods, such as PhenoGraph.

Developing a Novel Indium(III) Agent Based on Human Serum Albumin Nanoparticles: Integrating Bioimaging and Therapy.

To effectively integrate diagnosis and therapy for tumors, we proposed to develop an indium (In) agent based on the unique property of human serum albumin (HSA) nanoparticles (NPs). A novel In(III) quinoline-2-formaldehyde thiosemicarbazone compound (C5) was optimized with remarkable cytotoxicity and fluorescence to cancer cells . An HSA-C5 complex NP delivery system was then successfully constructed.

Integrated microfluidic single-cell immunoblotting chip enables high-throughput isolation, enrichment and direct protein analysis of circulating tumor cells.

Effective capture and analysis of a single circulating tumor cell (CTC) is instrumental for early diagnosis and personalized therapy of tumors. However, due to their extremely low abundance and susceptibility to interference from other cells, high-throughput isolation, enrichment, and single-cell-level functional protein analysis of CTCs within one integrated system remains a major challenge. Herein, we present an integrated multifunctional microfluidic system for highly efficient and label-free CTC isolation, CTC enrichment, and single-cell immunoblotting (ieSCI).

Developing a Novel Anticancer Gold(III) Agent to Integrate Chemotherapy and Immunotherapy.

To effectively treat gastric cancer, we innovatively attempted to develop a metal agent to integrate immunotherapy and chemotherapy by dual targeting the cellular components in the tumor microenvironment (TME) based on the specific residue of human serum albumin (HSA) nanoparticles (NPs). We synthesized a series of Au(III) α-N-heterocyclic thiosemicarbazone compounds and obtained a Au agent () with remarkable cytotoxicity to gastric cancer cells; moreover, we successfully constructed a novel complex NP delivery system. Importantly, the results showed that / NPs effectively inhibited gastric tumor growth and NPs enhanced the therapeutic efficiency, bioavailability, and targeting ability compared with those of alone.

Single-Cell Immunoblotting based on a Photoclick Hydrogel Enables High-Throughput Screening and Accurate Profiling of Exogenous Gene Expression.

Fast and accurate profiling of exogenous gene expression in host cells is crucial for studying gene function in cellular and molecular biology, but still faces the challenge of incomplete co-expression of reporter genes and target genes. Here, a single-cell transfection analysis chip (scTAC) is presented, which is based on the in situ microchip immunoblotting method, for rapid and accurate analysis of exogenous gene expression in thousands of individual host cells. scTAC not only can assign information of exogenous gene activity to specific transfected cells, but enables the acquisition of continuous protein expression even in low co-expression scenarios.

Dithiocarbazate-Copper Complexes for Bioimaging and Treatment of Pancreatic Cancer.

Anticancer agents that present nonapoptotic cell death pathways are required for treating apoptosis-resistant pancreatic cancer. Here, we synthesized three fluorescent dithiocarbazate-copper complexes, {[Cu(L)(Cl)] , [Cu(L)(NO)] , and [CuCu(L)(Br)] }, to assess their antipancreatic cancer activities. Complexes showed significantly greater cytotoxicity toward several pancreatic cancer cell lines with better IC than those of the HL ligand and cisplatin.

Designing biotin-human serum albumin nanoparticles to enhance the targeting ability of binuclear ruthenium(III) compound.

On the one hand, to obtain a novel next-generation anticancer metal agent; on the other hand, to improve the targeting ability and decrease side effects of metal agent, we proposed to design active-targeting human serum albumin (HSA) nanoparticles (NPs) to achieve the end. Thus, we not only designed and synthesized two ruthenium (Ru) thiosemicarbazone compounds (C1 and C2) but also succeeded in constructing active Biotin-HSA NPs for Ru(III) compounds. Importantly, Biotin-HSA-C2 NPs not only possessed a stronger capacity for killing MCF-7 cells and inhibiting their migration versusC2 alone but also increased accumulation compared to non-malignant WI-38 cells.

Label-free Separation of Circulating Tumor Cells Using a Self-Amplified Inertial Focusing (SAIF) Microfluidic Chip.

Circulating tumor cells (CTCs) are rare cells existing in the bloodstream with a relatively low number, which facilitate as a predictor of cancer progress. However, it is difficult to obtain highly purified intact CTCs with desired viability due to the low percentage of CTCs among blood cells. In this work, we demonstrate a novel self-amplified inertial focused (SAIF) microfluidic chip that enables size-based, high-throughput, label-free separation of CTCs from a patient's blood.

Synthesis of a series of novel In(III) 2,6-diacetylpyridine bis(thiosemicarbazide) complexes: structure, anticancer function and mechanism.

The anticancer function and anticancer mechanism of indium (In) complexes still remain mysterious to date. Furthermore, it is greatly challenging to design a multi-functional metal agent that not only kills cancer cells but also inhibits their invasion and metastasis. Thus, to develop novel next-generation anticancer metal agents, we designed and synthesized a series of novel In(iii) 2,6-diacetylpyridine bis(thiosemicarbazide) complexes (C1-C4) for the first time and then investigated their structure-activity relationships with human urinary bladder cancer (T-24) cells.

Developing a Novel Gold(III) Agent to Treat Glioma Based on the Unique Properties of Apoferritin Nanoparticles: Inducing Lethal Autophagy and Apoptosis.

Effective delivery of anticancer agents across the blood-brain barrier (BBB) required innovative strategies to achieve glioma regression. To resolve this problem, we proposed to develop a metal agent that target and treat glioma based on the unique property of apoferritin (AFt) nanoparticles (NPs). Thus, we synthesized a series of Au(III) 3-(4-metyl piperidine)thiosemicarbazides compounds and analyzed their structure-activity relationships, obtaining a Au agent (C6) with remarkable cytotoxicity in glioma.

Metal-Labeled Aptamers as Novel Nanoprobes for Imaging Mass Cytometry Analysis.

Imaging mass cytometry (IMC) is an emerging imaging technology that exploits the multiplexed analysis capabilities of the CyTOF mass cytometer to make spatially resolved measurements for tissue sections. In a comprehensive view of tissue composition and marker distribution, recent developments of IMC require highly sensitive, multiplexed assays. Approaching the sensitivity of the IMC technique, we designed a novel type of biocompatible metal-labeled aptamer nanoprobe (MAP), named Er-A10-3.

Human Serum Albumin-Based Dual-Agent Delivery Systems for Combination Therapy: Acting against Cancer Cells and Inhibiting Neovascularization in the Tumor Microenvironment.

To cause tumor regression by acting against cancer cells and inhibiting neovascularization in the tumor microenvironment, we constructed human serum albumin (HSA)-based delivery systems of 2-acetylpyridine-4,4-dimethyl-3-thiosemicarbazone-copper(II) [Cu(Ap44mT)]Cl and paclitaxel to improve both the therapeutic efficacy and the targeting ability . X-ray crystallography and matrix-assisted laser desorption/ionization time-of-flight mass spectra confirmed that [Cu(Ap44mT)]Cl complexed with HSA, whereas paclitaxel was tethered to the HSA complex by a linker sensitive to the active matrix metalloproteinase 2 (MMP2) protein. Up to 78% of paclitaxel was released from HSA within 2 h owing to MMP2 protein cleavage.