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Copper-cysteamine nanoparticle-mediated microwave dynamic therapy improves cancer treatment with induction of ferroptosis

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Bioactive Materials 2023年第6期24卷 322-330页

作者： Hui Zhou Zhongtao Liu Zijian Zhang Nil Kanatha Pandey eric amador William Nguyen Lalit Chudal Li Xiong Wei Chen Yu Wen Department of General Surgery Second Xiangya HospitalCentral South UniversityChangsha410011China Department of Physics The University of Texas at ArlingtonArlingtonTX76019-0059USA

Photodynamic Therapy(PDT)holds a great promise for cancer patients,however,due to the hypoxic characteristics of most solid tumors and the limited penetration depth of light in tissues,the extensive clinical application of PDT is limited.Herein,we report microwave induced copper-cysteamine(Cu-Cy)nanoparticles-based PDT as a promising cancer treatment to overcome cancer resistance in combination with ferroptosis.The treatment efficiency of Cu-Cy-mediated microwave dynamic therapy(MWDT)tested on HCT15 colorectal cancer(CRC)cells via cell titer-blue cell viability assay and live/dead assay reveal that Cu-Cy upon MW irradiation can effectively destroy HCT15 CRC cells with average IC-50 values of 20μg/mL.The cytotoxicity of Cu-Cy to tumor cells after MW stimulation can be alleviated by ferroptosis inhibitor.Furthermore,Cu-Cy mediated MWDT could deplete glutathione peroxide 4(GPX4)and enhance lipid peroxides(LPO)and malondialdehyde(MDA).Our findings demonstrate that MW-activated Cu-Cy killed CRC cells by inducing ferroptosis.The superior in vivo antitumor efficacy of the Cu-Cy was corroborated by a HCT15 tumor-bearing mice model.Immunohistochemical experiments showed that the GPX4 expression level in Cu-Cy+MW group was significantly lower than that in other groups.Overall,these findings demonstrate that Cu-Cy nanoparticles have a safe and promising clinical application prospect in MWDT for deep-seated tumors and effectively inhibit tumor cell proliferation by inducing ferroptosis,which provides a potential solution for cancer resistance.

关键词： Cu-Cy Microwave PDT Cell death Colorectal cancer Ferroptosis

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The exploration of quantum dot-molecular beacon based MoS_(2) fluorescence probing for myeloma-related Mirnas detection

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Bioactive Materials 2022年第11期7卷 360-368页

作者： Jing Jing Wang Ying Liu Zhou Ding Le Zhang Caiqin Han Changchun Yan eric amador Liqin Yuan Ying Wu Chunyuan Song Ying Liu Wei Chen Jiangsu Key Laboratory of Advanced Laser Materials and Devices School of Physics and Electronic EngineeringJiangsu Normal UniversityXuzhou221116China Jiangsu Key Laboratory for Biosensors Institute of Advanced Materials(IAM)Nanjing University of Posts&TelecommunicationsNanjing210023China Department of Physics The University of Texas at ArlingtonArlingtonTX76019-0059USA Department of General Surgery The Second Xiangya HospitalCentral South UniversityChangShaHu’nan410011China Medical Technology Research Centre Chelmsford CampusAnglia Ruskin UniversityChelmsfordCM11SQUK

Highly sensitive and reliable detection of multiple myeloma remains a major challenge in liquid biopsy. Herein, for the first time, quantum dot-molecular beacon (QD-MB) functionalized MoS_(2) (QD-MB @MoS_(2)) fluorescent probes were designed for the dual detection of multiple myeloma (MM)-related miRNA-155 and miRNA-150. The results indicate that the two probes can effectively detect miRNA-155 and miRNA-150 simultaneously with satisfactory recovery rates, and the limit of detections (LODs) of miRNA-155 and miRNA-150 in human serum are low to 7.19 fM and 5.84 fM, respectively. These results indicate that our method is the most sensitive detection so far reported and that the designed fluorescent probes with signal amplification strategies can achieve highly sensitive detection of MM-related miRNAs for MM diagnosis.

关键词： Multiple myeloma miRNA-155 miRNA-150 Duplex-specific nuclease(DSN) Quantum dot MoS_(2) Molecular beacon

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Aggregation-induced emission luminogens for highly effective microwave dynamic therapy

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Bioactive Materials 2022年第1期7卷 112-125页

作者： Nil Kanatha Pandey Wei Xiong Lingyun Wang Wei Chen Brian Bui Jian Yang eric amador Mingli Chen Christina Xing Aseem Atul Athavale Yaowu Hao Wirya Feizi Lloyd Lumata Department of Physics The University of Texas at ArlingtonArlingtonTX 76019USA Key Laboratory of Functional Molecular Engineering of Guangdong Province School of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhou510640China Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA16802USA Department of Chemistry College of SciencesNortheastern UniversityBox 332Shenyang 110819China Department of Materials Science and Engineering The University of Texas at ArlingtonArlingtonTX 76019USA Department of Physics The University of Texas at Dallas800 West Campbell RoadRichardsonTX 75080USA

Aggregation-induced emission luminogens(AIEgens)exhibit efficient cytotoxic reactive oxygen species(ROS)generation capability and unique light-up features in the aggregated state,which have been well explored in image-guided photodynamic therapy(PDT).However,the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications.Coincidentally,microwaves(MWs)show a distinct advantage for deeper penetration depth in tissues than light.Herein,for the first time,we report AIEgen-mediated microwave dynamic therapy(MWDT)for cancer treatment.We found that two AIEgens(TPEPy-I and TPEPy-PF6)served as a new type of microwave(MW)sensitizers to produce ROS,including singlet oxygen(1O2),resulting in efficient destructions of cancer cells.The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22μM,respectively.Overall,the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT,but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome,thus reducing the occurrence of side-effects of MW radiation.

关键词： AIEgens Microwaves Photodynamic therapy Reactive oxygen species Microwave ablation Cancer treatment Singlet oxygen

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Study of copper-cysteamine based X-ray induced photodynamic therapy and its effects on cancer cell proliferation and migration in a clinical mimic setting

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Bioactive Materials 2022年第1期7卷 504-514页

作者： Xiangyu Chen Jiayi Liu Ya Li Nil Kanatha Pandey Taili Chen Lingyun Wang eric Horacio amador Weijun Chen Feiyue Liu Enhua Xiao Wei Chen Department of Radiology The Second Xiangya Hospital of Central South UniversityChangshaHunanChina Department of Physics The University of Texas at ArlingtonArlingtonTX76019USA Department of Oncology Xiangya HospitalCentral South UniversityChangshaHunan Province410011China Department of Oncology The Second Xiangya Hospital of Central South UniversityChangshaHunanChina

Copper-cysteamine as a new generation of sensitizers can be activated by light,X-rays,microwaves,or ultrasound to produce reactive oxygen species.X-ray induced photodynamic therapy(X-PDT)has been studied extensively;however,most of the studies reported so far were conducted in the laboratory,which is not conducive to the clinical translation conditions.In this contribution,for the first time,we investigated the treatment efficiency of copper-cysteamine(Cu-Cy)based X-PDT by mimicking the clinical conditions with a clinical linear accelerator and building deep-seated tumor models to study not only the effectiveness but also its effects on the cell migration and proliferation in the level of the cell,tissue,and animal.The results showed that,without X-ray irradiation,Cu-Cy nanoparticles(NPs)had a low toxicity in HepG2,SK-HEP-1,Li-7,and 4T1 cells at a concentration below 100 mg/L.Interestingly,for the first time,it was observed that Cu-Cy mediated X-PDT can inhibit the proliferation and migration of these cell lines in a dose-dependent manner.Antigen markers of migration and cell proliferation,proliferating cell nuclear antigen(PCNA)and E-cadherin,from tumor tissue in the X-PDT group were remarkably different from that of the control group.Furthermore,the MRI assessment showed that the Cu-Cy based X-PDT inhibited the growth of deeply located tumors in mice and rabbits(p<0.05)without any obvious toxicities in vivo.Overall,these new findings demonstrate that Cu-Cy NPs have a safe and promising clinical application prospect in X-PDT to improve the efficiency of radiotherapy(RT)for deep-seated tumors and effectively inhibit tumor cell proliferation and migration.

关键词： Copper-cysteamine Nanoparticle Photodynamic therapy X-ray Cell migration Proliferation

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