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Multifunctional theranostic nanoparticles for multi-modal imaging-guided CAR-T immunotherapy and chemo-photothermal combinational therapy of non-Hodgkin's lymphoma

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机构: [1]Shanghai Jiao Tong Univ, Dept Radiol, Ruijin Hosp, Sch Med, Shanghai 200025, Peoples R China [2]Shanghai Jiao Tong Univ, Natl Res Ctr Translat Med Shanghai, Shanghai Inst Hematol, State Key Lab Med Genom,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China [3]Shanghai Jiao Tong Univ, Dept Radiol, Tongren Hosp, Sch Med, Shanghai 200050, Peoples R China [4]Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China [5]Shanghai Jiao Tong Univ, Inst Med Robot, Shanghai 200240, Peoples R China
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Accurate and effective tumor diagnosis, detection, and treatment are key for improving the survival rates of patients. Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable clinical success in eradicating hematologic malignancies. However, the hostile microenvironment in solid tumors severely prevents CAR-T cells from migrating and from infiltrating and killing malignant cells. Tumor microenvironment modulation strategies have attracted much attention in the field of cancer immunotherapy. Multifunctional nanoplatforms that integrate the advantages of different therapeutic techniques can allow for the multimodal synergistic treatment of tumors. In this study, a biocompatible, tumor-targeting, on-demand approach combining CAR-T cell immunotherapy and a chemo-photothermal therapy nanoplatform (FA-Gd-GERTs@Ibrutinib) based on gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) has been developed for multimodal imaging, and it provides a reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction. In our study, folate (FA) receptor targeted molecules are used to improve the accuracy and sensitivity of computed tomography/magnetic resonance/Raman multimodal tumor imaging. The photothermal effect of the nanoprobe can promote the angiogenesis of lymphoma tissue, destroy the extracellular matrix, loosen compact tissue, stimulate chemokine secretion, and effectively enhance the infiltration ability in the case of non-Hodgkin's lymphoma, without dampening the CD19 CAR-T cell activity. The treatment results in tumor-bearing mice proved the existence of excellent synergistic therapy; photothermal therapy improves the accumulation and effector function of CAR-T cells within solid tumors. It is believed that multifunctional nanomaterials with targeted multi-modal imaging capabilities that support combination therapy can provide an efficient route for accurate diagnosis and efficient treatment.

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出版当年[2021]版:
大类 | 2 区 工程技术
小类 | 2 区 材料科学:生物材料
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 材料科学:生物材料
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出版当年[2020]版:
Q1 MATERIALS SCIENCE, BIOMATERIALS
最新[2023]版:
Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Shanghai Jiao Tong Univ, Dept Radiol, Ruijin Hosp, Sch Med, Shanghai 200025, Peoples R China
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通讯机构: [4]Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China [5]Shanghai Jiao Tong Univ, Inst Med Robot, Shanghai 200240, Peoples R China
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