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Aging and Disease · 2024 · IF 7

An Antibody-directed and Immune Response Modifier-augmented Photothermal Therapy Strategy Relieves Aging via Rapid Immune Clearance of Senescent Cells

Jiamei Han,Judun Zheng,Qian Li,Huanle Hong,Jing Yao,Jiao Wang,Robert Chunhua Zhao

Cellular senescence is an irreversible and multifaceted process inducing tissue dysfunction and organismal aging, and thus the clearance of senescent cells can prevent or delay the onset of aging-related pathologies. Herein, we developed an augmented photothermal therapy strategy integrated with an antibody against β2-microglobulin (aB2MG) and an immune adjuvant imiquimod (R837) to effectively accelerate senescent cell apoptosis and clearance under a near-infrared light. With this strategy, the designed CroR@aB2MG enables the targeting of senescent cells and the application of photothermal therapy concomitantly, the initiation of immune clearance subsequently, and finally the realization of protective effects against senescence. Our results showed that the photo-induced heating effect caused senescent cells to quickly undergo apoptosis and the synchronous immune response accelerated the clearance of senescent cells in vitro and in vivo . Therefore, this photoactivated speedy clearing strategy may provide an efficient way for the treatment of senescence-related diseases by eliminating senescent cells with biomaterials.

研究领域: 生物医学 · 免疫学 · 老年医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2024 · IF 9.4

Tumor-targeted Delivery of Copper-manganese Biomineralized Oncolytic Adenovirus for Colorectal Cancer Immunotherapy

Yi-Shu Li,Lu-Yi Ye,Yan-Xi Luo,Wen-Jie Zheng,Jing-Xing Si,Xue Yang,You-Ni Zhang,Shi-Bing Wang,Hai Zou,Ke-Tao Jin,Tong Ge,Yu Cai,Xiao-Zhou Mou

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. Statement of significance : Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, Hypoxia effect, and Administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.

CAS / MDL: 7447-39-4 36309-88-3
研究领域: 肿瘤学 · 免疫学 · 生物医学工程 · 病毒学
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International Journal of Nanomedicine · 2022 · IF 7.033

Hybrid Cell Membrane-Functionalized Biomimetic Nanoparticles for Targeted Therapy of Osteosarcoma

Jia-Xin Cai,Ji-Hua Liu,Jun-Yong Wu,Yong-Jiang Li,Xiao-Han Qiu,Wen-Jie Xu,Ping Xu,Da-Xiong Xiang

Purpose In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo.Methods PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice.Results The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues.Conclusion PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.

CAS / MDL: 9002-89-5
研究领域: 纳米技术 · 药学 · 肿瘤学 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Nanozyme-nanoclusters in metal–organic framework: GSH triggered Fenton reaction for imaging guided synergistic chemodynamic-photothermal therapy

Fangfang Yu,Tingya Wang,Yihan Wang,Tengfei Liu,Hongjie Xiong,Liu Liu,Jiang Xiao,Xiaohui Liu,Hui Jiang,Xuemei Wang

It is of great significance to design functional nanomaterials with specific response to tumor microenvironments (TMEs), so as to achieve accurate imaging and efficient treatment of tumor. In this work, a TME-activated biomimetic nanocomposite with dual imaging capabilities of turn-on fluorescence imaging and photothermal imaging was constructed for high-sensitivity sensing of glutathione (GSH) and self-enhanced photothermal/chemodynamic synergistic therapy. The nanocomposite was designed by loading nanozyme MnO 2 and luminol gold nanoclusters on ZIF-8 (Z-M-LA), which was then coated with 4T1 cell membrane (Z-M-LA@CM). The biomimetic membrane decoration was used to escape immune clearance and maintain good biocompatibility and targeting ability. The fluorescence of luminol gold nanoclusters quenched by MnO 2 can be recovered in vivo through MnO 2 degradation by GSH, which enables the TME-activated visualization of tumor. Simultaneously, MnO 2 shows peroxidase-like activity after being degraded by GSH and the released Mn 2+ can catalyze H 2 O 2 to generate abundant hydroxyl radicals (·OH) to realize self-enhanced photothermal/chemodynamic synergistic therapy. Furthermore, Z-M-LA@CM was also investigated to induce immune effect in vivo and it exhibited good pH-responsive degradation behavior, which could remain stable under alkaline conditions (pH = 7.4) and be degraded in acidic solutions (pH = 5.6). These properties make Z-M-LA@CM an appealing biodegradable nanotherapeutic agent for tumor precise diagnosis and therapy.

研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 材料科学 · 生物化学 · 诊疗一体化
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