Nano Research
·
2024
·
IF 9.5
Zhao Ze Qiang,Chen Bo Zhi,Gan Jia Li,Feng Yun Hao,Liang Ling,Yu Lingyun,Wang Zi Yi,Abbaszadeh Samin,Shahbazi Mohammad-Ali,Yu Ruixing,Guo Xin Dong
Modulating the immune microenvironment to establish sustained positive feedback within immune pathways represents a promising avenue for the treatment of autoimmunity. However, the precise and efficient delivery of therapeutic systems to the subcutaneous basal layer to modulate immune disorders is a major challenge in the treatment of autoimmune psoriasis. In this project, we introduce a dual-functional microneedle (DF-MN) designed to combine MNs with multiple release kinetics and immunotherapy, the programmed treatment is achieved through segmented design of the MN structure, realizing the unification of rapid and long-lasting treatment of autoimmune psoriasis. In vivo imaging results showed that GelMA@M-CSF showed fluorescent signals after 5 days of delivery to subcutaneous tissues, whereas HA@IL-13 showed minimal fluorescent signals after 2 days. The multistage release behavior of MNs and the diffusion mechanism of drugs were explained at the molecular level, in combination with coarse-grained molecular dynamics. Additionally, DF-MN can successfully induce macrophage reprogramming in vitro and ameliorate overall symptoms in a psoriasis mice model, suggesting that it has the potential to be an effective strategy for the treatment of psoriasis and portends to be a transformative platform for the treatment of other autoimmune diseases.
研究领域:
生物医学工程
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免疫学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Jun-Long Liang,Xiao-Kang Jin,Guo-Feng Luo,Shi-Man Zhang,Qian-Xiao Huang,Yan-Tong Lin,Xin-Chen Deng,Jia-Wei Wang,Wei-Hai Chen,Xian-Zheng Zhang
Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, “eat me” signal calreticulin (CRT) was upregulated, while the “don’t eat me” signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.
研究领域:
生物医学工程
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癌症免疫疗法
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药学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2021
·
IF 5.458
Yuying Zhang,Anqi Guo,Cheng Lyu,Ran Bi,Zhaozhao Wu,Wenjing Li,Peng Zhao,Yudi Niu,Jie Na,Jianzhong Jeff Xi,Yanan Du
Summary It is still a challenge for synthesizing ‘cellular niche-mimics’ in vitro with satisfactory reproducibility and fidelity to recreate the natural niche components (e.g., extracellular matrices and soluble factors) for stem cell cultivation. Inspired by the massive amplification of hepatic progenitor cells during liver fibrosis in vivo , here we optimized the in vitro liver fibrotic niches and subsequently harvested their bioactive ingredients as niche extracts (NEs). The fibrosis-relevant NE marginally outperformed Matrigel for phenotype maintenance of human embryonic stem cell (hESC)-derived hepatoblasts (HBs) and recapitulation of the pathological angiogenesis of hESC-derived endothelial cells both in 2D culture and 3D liver organoids. Finally, defined NE components (i.e., collagen III, IV, IL-17, IL-18 and M-CSF) were resolved by the quantitative proteomics which exhibited advantage over Matrigel for multi-passaged HB expansion. The pathology-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.
研究领域:
干细胞生物学
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组织工程
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细胞微环境
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蛋白质组学
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类器官培养
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 27
·2201834
·
IF 17.521
Xiao Sang,Tong Gao,Xiaoqing Liu,Yelong Shen,Lili Chang,Shunli Fu,Han Yang,Huizhen Yang,Weiwei Mu,Shuang Liang,Zipeng Zhang,Na Zhang,Yongjun Liu
Photothermal therapy (PTT) is a promising strategy for cancer treatment, but its clinical application relies heavily on accurate tumor positioning and effective combination. Nanotheranostics has shown superior application in precise tumor positioning and treatment, bringing potential opportunities for developing novel PTT-based therapies. Here, a nanotheranostic agent is proposed to enhance magnetic resonance imaging (MRI)/ near-infrared fluorescence imaging (NIRFI) imaging-guided photo-induced triple-therapy for cancer. Thermosensitive liposomes co-loaded with SPIONs/IR780 and Abemaciclib (SIA-TSLs), peptide ACKFRGD, and click group 2-cyano-6-amino-benzothiazole (CABT) are co-modified on the surface of SIA-TSLs to form SIA- α TSLs. ACKFRGD can be hydrolyzed to expose the 1, 2-thiolamino groups in the presence of cathepsin B in tumors, which click cycloaddition with the cyano group on CABT, resulting in the formation of SIA- α TSLs aggregates. The aggregation of SIA- α TSLs in tumors enhances the MRI/NIRFI imaging capability and enables precise PTT. Photo-induced triple-therapy enhances precision cancer therapy. First, PTT ablates specific tumors and induces ICD via localized photothermal. Second, local tumor heating promotes the rupture of SIA- α TSLs, which release Abemaciclib to block the tumor cell cycle and inhibit Tregs proliferation. Third, injecting GM-CSF into tumor tissue leads to recruitment of dendritic cells and initiation of antitumor immunity. Collectively, these results present a promising nanotheranostic strategy for future cancer therapy.
研究领域:
生物医学工程
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癌症治疗
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医学影像
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纳米技术
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药学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）