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DMMA
Small · 2024 · IF 13

Molecular Engineering of AIE-Active Photosensitizers with High Biosafety for Effect Extracellular Antibacteria

Ke Ma,Jianxia Dong,Dingyuan Yan,Deliang Wang,Yuanwei Wang,Jianxing Wang,Dong Wang,Hui Tan,Ben Zhong Tang

Developing versatile photosensitizers to actualize selective antibacteria over normal cells presents an appealing yet significantly challenging task. In this study, a novel photosensitizer named DMMA-SCPI is rationally designed and facilely synthesized, which is demonstrated as a type-I photosensitizer featured by aggregation-induced emission tendency. DMMA-SCPI is capable of effectively eliminating both Galanz positive bacteria and Galanz negative bacteria in vitro and in vivo, and showed insignificant injury to normal cells and tissues, probably resulting from its pyridinium halide that has stronger adsorption property on negatively charged bacteria compared to normal cells, as well as its suitable antimicrobial activity. The antimicrobial activity of pyridinium salt type photosensitizer depends on the adsorptive activities on the surface of bacterial cells as well as the antimicrobial activity of the reactive oxygen species (ROS). Among three photosensitizers, DMMA-SCPI has better water solubility, which provides greater surface activity to adsorb bacteria. Moreover, DMMA-SCPI produces more superoxide anion radicals as ROS, which has proper antimicrobial activity with high biosafety for effect extracellular antibacteria.

研究领域: 分子工程 · 生物医学 · 光动力疗法
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CHINESE JOURNAL OF POLYMER SCIENCE · 2023 · IF 4.3

pH Induced Self-assembly of AIE Fluorescent Probe for Tumor Imaging

Xiang Jing-Yuan,Zhang Wen-Long,Li He-Ting,He Ya-Ning

This work reported an AIE fluorescent probe for tumor imaging based on the pH induced self-assembly strategy. The fluorescent probe was composed of an acid-responsive soluble copolymer PEG- b -PAMA-DMMA with a maleic acid amide group and an anionic soluble aggregation-induced emission fluorogen (AIEgen) TPE-2SO 3 − . The polymer could be transformed into a protonated amine-containing polymer after the hydrolysis of maleic acid amide in acidic tumor microenvironment, which would be further self-assembled with TPE-2SO 3 − to form aggregated nanoparticles. The transition of TPE-2SO 3 − from dispersed state to aggregated state led to an obvious increase in fluorescence intensity due to its AIE characteristics.

CAS / MDL: 2002-24-6
研究领域: 材料科学 · 生物医学工程 · 癌症研究 · 纳米技术
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Acta Biomaterialia · 2019 · IF 6.638

Role of charge-reversal in the hemo/immuno-compatibility of polycationic gene delivery systems

Qi Yang,Shuo Liu,Xin Liu,Zonghua Liu,Wei Xue,Yi Zhang

As an effective and well-recognized strategy used in many delivery systems, such as polycation gene vectors , charge reversal refers to the alternation of vector surface charge from negative (in blood circulation) to positive (in the targeted tissue) in response to specific stimuli to simultaneously satisfy the requirements of biocompatibility and targeting. Although charge reversal vectors are intended to avoid interactions with blood in their application, no overall or systematic investigation has been carried out to verify the role of charge reversal in the blood compatibility. Herein, we comprehensively mapped the effects of a typical charge-reversible polycation gene vector based on pH-responsive 2,3-dimethylmaleic anhydride (DMMA)-modified polyethylenimine (PEI)/pDNA complex in terms of blood components, coagulation function, and immune response as compared to conventional PEGylated modification. The in vitro and in vivo results displayed that charge-reversal modification significantly improves the PEI/pDNA-induced abnormal effect on vascular endothelial cells, platelet activation , clotting factor activity, fibrinogen polymerization, blood coagulation process, and pro-inflammatory cytokine expression. Unexpectedly, (PEI/pDNA)-DMMA induced the cytoskeleton impairment-mediated erythrocyte morphological alternation and complement activation even more than PEI/pDNA. Further, transcriptome sequencing demonstrated that the overexpression of pro-inflammatory cytokines was correlated with vector-induced differentially expressed gene number and mediated by inflammation-related signaling pathways (MAPK, NF-κB, Toll-like receptor, and JAK-STAT) activation. By comparison, charge-reversal modification improved the hemocompatibility to a greater extent than dose PEGylation except for erythrocyte rupture. Nevertheless, it is inferior to mPEG modification in terms of immunocompatibility. These findings provide comprehensive insights to understand the molecular mechanisms of the effects of charge reversal on blood components and their function and to provide valuable information for its potential applications from laboratory to clinic. Statement of Significance The seemingly revolutionary charge reversal strategy has been believed to possess stealth character with negative charge eluding interaction with blood components during circulation. However to date, no overall or systematic investigation has been carried out to verify the role of charge-reversal on the blood/immune compatibility, which impede their development from laboratory to bedside. Therefore, we comprehensively mapped the effects of a typical charge-reversible polycationic gene vector on blood components (vascular endothelial cell, platelet, clotting factors, fibrinogen, RBCs and coagulation function) and immune response (complement and pro-inflammatory cytokines) at cellular and molecular level in comparison to PEGylation modification. These findings help to elucidate the molecular mechanisms for the effects of charge-reversal on blood components and functions, and provide valuable information for the possible application in clinical settings.

CAS / MDL: 589-91-3
研究领域: 药学 · 生物医学工程 · 分子生物学 · 免疫学 · 血液学
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