CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
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2022
·Vol. 38
·期 4
·949-956
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IF 2.726
Ruan Yawen,Huang Peiling,Yan Jiangyu,Li Guorui,Huang Jing
Targeted prodrug strategy, which utilizes the endogenous biomarkers in cancer cells as activators to release the active drug, has been well established either in the fundamental research or the clinical treatment. However, many prodrugs suffer from safety concern due to “off-target activation”. Dual or multiple biomarkers triggered prodrug may provide an effective strategy to overcoming the “off-target effect”. Melanoma cells have both high levels of reactive oxygen species(ROS) and tyrosinase(TYR), which makes them significantly different from other tumor cells and normal cells. Here we reported a series of quinazolinone-aryl boronic acid/ester-based prodrugs, which can be activated by the cascade of ROS and TYR and selectively kill melanoma cells. The structure-activity relationship(SAR) analysis revealed that mitochondria-targeting property was vital for their cytotoxicity and the dual activated effector played a significant role in their selectivity towards melanoma cells. Among these candidates, compound 4 b showed the highest toxicity to B16, leading to an imbalance of the redox system in melanoma cells, causing mitochondrial DNA damage, and then promoting melanoma cells death.
研究领域:
肿瘤学
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药物化学
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分子生物学
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药理学
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DOI
高影响因子
PROTEIN JOURNAL
·
2021
·Vol. 40
·期 5
·709-720
·
IF 2.371
Jiang Xuan,Zhang Xin,Fu Chao,Zhao Ruili,Jin Tianming,Liu Mengyue,Pan Chenhao,Li Liu An,Ma Jifei,Yu Enyuan,YU Xiaoxue,Hu Ye
Malignant melanoma, an increasingly common form of skin cancer, poses a significant threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. In this work, a new anti-tumor peptide, temporin La (T-La), was selected from a cDNA library generated from bullfrog skin. Two new derivative antitumor peptides, T-La (S) and T-La (FS), were designed by bioinformatics analysis and coupled with the RGD small molecule peptide to create chimeric RGD peptides, (RGD-T-La [S] and RGD-T-La [FS]). Preliminary experiments showed that the new antitumor peptides had significant antitumor effects. After coupling to the chimeric RGD peptide, the targeted treatment of mouse melanoma was significantly improved. Our data demonstrate that the 4 peptides tested herein significantly inhibited the proliferation, migration, and invasion of B16F10 cells; with an increase in polypeptide concentration, the proportion of melanoma cells in the G0/G1 phase decreased or increased significantly, respectively, the reactive oxygen species (ROS) content increased significantly, the mitochondrial membrane potential decreased significantly, and the expression of pro-apoptotic Bax, Caspase-3, and Caspase-9 increased, and anti-apoptotic Bcl-2 decreased significantly. Tyr and MITF genes were significantly downregulated. In conclusion, the use of these new anti-tumor peptides, when combined with a chimeric RGD peptide, may increase ROS levels and decrease mitochondrial membrane potential by inhibiting the activity of mitochondria, thus releasing apoptosis-promoting factors in B16F10 cells. The present study describes a new potential strategy for the application of promising peptides in the treatment of various cancers.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Dechan Lu,Qun Zhang,Zufang Huang,Yudong Lu,Shangyuan Feng,Ruiyun You,Minling Li,Shaoqin Zhang
Tyrosinase (TYR) is a polyphenol oxidase that regulates melanin biosynthesis . Abnormal levels of TYR have been confirmed closely associated with melanoma cancer and other diseases, making the establishment of highly sensitive and accurate quantitative detection of TYR is thus essential for fundamental research and clinical applications. Herein, we proposed a new strategy that combines surface-enhanced Raman scattering (SERS) with Dopamine (DA) and Prussian blue (PB) functionalized gold-gold hybrid nanoparticles for TYR detection. DA is oxidized to dopaquinone with the presence of TYR, leading to the consumption of DA in the reaction solution and the corresponding decrease in DA characteristic peak intensity at 1480 cm −1 . Our SERS quantitative assay of TYR with “on-off” sensing strategy yields an excellent limit of detection (LOD) of 3 × 10 −3 U mL −1 in a linear range of 10 −3 to 100 U mL −1 . In particular, the intensity ratio of 1480 cm −1 to 2121 cm −1 allows us to achieve remarkably reliable quantitative detection of TYR, with the 2121 cm −1 peak intensity of the standard internal (IS) molecule PB being used to correct SERS signal fluctuations. Furthermore, our proposed assay has been successfully demonstrated to quantify TYR spiked in human serum samples, with excellent percentage recovery of 90.0–110.6 %. The potential of our ratiometric SERS strategy for the performance evaluation of TYR inhibitors has also been verified. Our work is therefore expected to provide a new route for accurate and reliable monitoring of TYR activity in the complex biological environment.
研究领域:
分析化学
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生物医学工程
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Shuai Chen,Haifeng Chen,Lindan Tan,Vahid Serpooshan
Adhesive tissue engineering scaffold (ATES) devices can be secured on tissues by relying on their intrinsic adhesive properties, hence, avoiding the complications such as host tissue/scaffold damages that are associated with conventional scaffold fixation methods like suturing or bioglue. This study introduces a new generation of three-dimensional (3D) bioprinted ATES systems for use as cardiac patches to regenerate the adult human heart. Tyramine-modified methacrylated hyaluronic acid (HAMA-tyr), gelatin methacrylate (GelMA), and gelatin were used to create the hybrid bioink formulation with self-adhesive properties. ATESs were bioprinted and further modified to improve the adhesion properties. In-depth characterization of printing fidelity, pore size, mechanical properties, swelling behavior, as well as biocompatibility was used to create ATESs with optimal biological function. Following in vitro testing, the ATESs were tested in a mouse model of myocardial infarction to study the scaffold adhesive strength in biological milieu. The method developed in this study can be used to manufacture off-the-shelf ATESs with complex cellular and extracellular architecture, with robust potential for clinical translation into a variety of personalized tissue engineering and regenerative medicine applications.
研究领域:
组织工程
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再生医学
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心血管研究
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生物打印
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生物材料
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产品关联
DOI
PubMed
高影响因子
Biofabrication
·
2020
·Vol. 12
·期 4
·045003
·
IF 8.213
Huimin He,Duo Li,Zifeng Lin,Liuqi Peng,Jirong Yang,Mingming Wu,Delin Cheng,Haobo Pan,Changshun Ruan
The development of exceptional bioinks with excellent printability, high fidelity, and excellent cell viability maintenance for extrusion bioprinting remains a major challenge. Gelatin is an ideal candidate bioink due to its biocompatibility, biodegradability, and non-immunogenicity. However, its inherently low viscosity and unstable physical gelation under physiological conditions make it unsuitable for direct extrusion bioprinting of tissue-like gelatin constructs with high fidelity. Herein, sequential chemical modification using reversible quadruple-hydrogen-bonded ureido-pyrimidinone (UPy) and enzyme-responsive tyramine moieties (Tyr) were devloped to endow the gelatin with a temperature-programmable viscosity and enzyme-controlled solidification, thus realizing enhanced printability and superior fidelity. As demonstrated in a proof-of-concept study, various cell-laden constructs were built based on our modified gelatin, including two-dimensional human bone marrow mesenchymal stem cell (hBMSC)-laden patterns, three-dimensional interconnected hBMSC-laden scaffolds, a reversible twisting-tension human-scale hBMSC-laden ear, a bicellular tibia-like construct containing hBMSCs and endothelial cells and a hexagonal prism-shaped hepatocyte-laden scaffold. The loaded cells in the construct have high viability of over 90% at 24 h, and show proliferation and protein secretion over one week, suggesting that Gel-UPy-Tyr-based constructs under physiological temperature not only can keep high fidelity, but also can support the growth and functions of the loaded cells.
研究领域:
生物医学工程
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组织工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）