ADVANCED MATERIALS
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2024
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IF 27.4
Qingshuang Zou,Ke Liao,Guangchao Li,Xin Huang,Yongwei Zheng,Gun Yang,Min Luo,Evelyn Y. Xue,Chuanqing Lan,Shuai Wang,Yao Shen,Dixian Luo,Dennis K. P. Ng,Quan Liu
The infiltration and cytotoxicity of chimeric antigen receptor (CAR)-T cells are crucial for effective elimination of solid tumors. While metallo-immunotherapy is a promising strategy that can activate the antitumor immunity, its role in promoting CAR-T cell therapy remains elusive. The first single-element nanomaterial based on chromium nanoparticles (Cr NPs) for cancer photo-metallo-immunotherapy has been reported previously. Herein, an extended study using biodegradable polydopamine as a versatile carrier for these nanoparticles, enabling synergistic CAR-T cell therapy, is reported. The results show that these nanocomposites with or without further encapsulation of the anticancer drug alpelisib can promote the CAR-T cell migration and antitumor effect. Upon irradiation with near-infrared light, they caused mild hyperthermia that can “warm” the “cold” tumor microenvironment (TME). The administration of B7-H3 CAR-T cells to NOD severe combined immunodeficiency gamma mice bearing a human hepatoma or PIK3CA-mutated breast tumor can significantly inhibit the tumor growth after the induction of tumor hyperthermia by the nanocomposites and promote the secretion of serum cytokines, including IL-2, IFN-γ, and TNF-α. The trivalent Cr 3+ ions, which are the major degradation product of these nanocomposites, can increase the CXCL13 and CCL3 chemokine expressions to generate tertiary lymphoid structures (TLSs) in the tumor tissues, facilitating the CAR-T cell infiltration.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
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生物医学工程
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2022
·Vol. 478
·期 3
·665-678
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IF 3.842
Qi Jie,Lv Ying,Zhong Ni-Er,Han Wen-Qi,Gou Qi-Ling,Sun Chao-Feng
Atherosclerotic morbidity is significantly higher in the diabetic population. Hyperglycemia, a typical feature of diabetes, has been proven to accelerate foam cell formation. However, the molecular mechanisms behind this process remain unclear. In this study, LPS and IFN-γ were used to convert THP-1-derived macrophages into M1 macrophages, which were then activated with ox-LDL in either high glucose or normal condition. We identified lipids within macrophages by Oil red O staining and total cholesterol detection. The genes involved in lipid absorption, efflux, inflammation, and metabolism were analyzed using qRT-PCR. The mechanisms of high glucose-induced foam cell formation were further investigated through metabolomics and transcriptomics analysis. We discovered that high glucose speed up lipid accumulation in macrophages (both lipid droplets and total cholesterol increased), diminished lipid efflux (ABCG1 down-regulation), and aggravated inflammation (IL1B and TNF up-regulation). Following multi-omics analysis, it was determined that glucose altered the metabolic and transcriptional profiles of macrophages, identifying 392 differently expressed metabolites and 293 differentially expressed genes, respectively. Joint pathway analysis suggested that glucose predominantly disrupted the glycerolipid, glycerophospholipid, and arachidonic acid metabolic pathways in macrophages. High glucose in the glyceride metabolic pathway, for instance, suppressed the transcription of triglyceride hydrolase (LIPG and LPL), causing cells to deposit excess triglycerides into lipid droplets and encouraging foam cell formation. More importantly, high glucose triggered the accumulation of pro-atherosclerotic lipids (7-ketocholesterol, lysophosphatidylcholine, and glycerophosphatidylcholine). In conclusion, this work elucidated mechanisms of glucose-induced foam cell formation via a multi-omics approach.
研究领域:
心血管疾病
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糖尿病
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分子生物学
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代谢
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炎症
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脂质代谢
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
·
IF 12.2
Yang Zhao,Minyu Wang,Weihua Chu
Per- and polyfluoroalkyl substances (PFAS) have been called "forever chemicals" due to their inherent chemical stability. Their potential toxic effects on aquatic animals and health risk assessments have not been fully elucidated. In this study, we investigated the toxic effects of PFASs at environmentally relevant concentrations (200 ng/L) on crucian carp ( Carassius auratus ). The results showed that PFAS reduced the comfort behaviour of crucian carp and was associated with reduced levels of acetylcholinesterase and dopamine in the brain. PFAS exposure also decreased the activities of total superoxide dismutase, catalase and glutathione peroxidase, while increasing the levels of malondialdehyde. PFAS caused over-expression of the pro-inflammatory cytokines TNF-α, IFN-γ and stress-related genes Caspase-3 , HSP-70 in the fish brain. Pathological staining showed that PFAS caused multifocal demyelination and perineural vacuolization in brain, intestinal tissue also showed reduced villus length and focal damage. PFASs altered the composition of the gut microbiota of crucian carp, significantly increasing the abundance of potentially pathogenic bacteria and the potential pathogenicity of the microbiota. It is suggested that PFASs may cause varying degrees of tissue damage by destabilising the gut microbiota. These results provide insights for assessing the toxicity of PFAS contaminants at aquatic environmental concentrations.
研究领域:
环境毒理学
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水生生物学
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微生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2016
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IF 7.441
Xiangting Zhuang,Tingting Wu,Yongdan Zhao,Xiaomeng Hu,Yuling Bao,Yuanyuan Guo,Qingle Song,Gao Li,Songwei Tan,Zhiping Zhang
Nanoimmunotherapy, the application of nanotechnology for sustained and targeted delivery of antigens to dendritic cells (DCs), has attracted much attention in stimulating antigen-specific immune response for antitumor therapy. In order to in situ deliver antigens to DCs for efficient antigen presentation and subsequent induction of strong cytotoxic T lymphocytes (CTL) response, here we developed a multi-peptide (TRP2 180–188 and HGP100 25–33 ) and toll-like receptor 4 agonist (monophosphoryl lipid A) codelivery system based on lipid-coated zinc phosphate hybrid nanoparticles (LZnP NPs). This delivery system equips with the chelating property of zinc to realize the high encapsulation efficiency with antigenic peptides and the influence on immune system with adjuvant-like feature. The combination of H-2K b and H-2D b -restricted peptides could provide multiple epitopes as the target of specific MHC alleles, making tumor more difficult to escape from the surveillance of immune system. The formulated LZnP nano-vaccine with the size of 30 nm and outer leaflet lipid exhibited antitumor immunity as the secretion of cytokines in vitro and increased CD8 + T cell response from IFN-γ ELISPOT analysis ex vivo . The antitumor effects were further evidenced from the prophylactic, therapeutic and metastatic melanoma tumor models compared with free antigens and single peptide-loaded nano-vaccines. These results validate the benefit of LZnP-based vaccine for antitumor immunity and indicate that co-delivery of tumor antigens along with adjuvant may be an optimized strategy for tumor immunotherapy .
研究领域:
纳米技术
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免疫学
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肿瘤学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zhiting Cao,Jianye Ren,Yuguan Huang,Tong Li,Zhen Wang,Zhangyi Miao,Jia Jia,Yang Ding
Epidermal immunotherapy represents an emerging treatment method for allergic diseases. Nevertheless, an unformidable obstacle for epidermal drug delivery is the dense stratum corneum of the skin. Here, iontophoresis technology is utilized for epidermal delivery of allergen protein. Briefly, an iontophoresis patch consists of conductive nanofiber polypyrrole (PPy) and polyvinyl alcohol (PVA) by electrospinning technology, onto which cationic lipid dioctadecyl–dimethylammonium bromide vesicles containing ovalbumin (DDA@OVA) are loaded via electrospraying technology, forming a stable in situ composite structure. Compared with DDA@OVA/PVA, DDA@OVA/PPy-PVA demonstrated a significant increase in both allergen release and penetration into the epidermis. Ultimately, a high-level activation of antigen-presenting cells is facilitated. Importantly, DDA@OVA/PPy-PVA induces a significant increase in the levels of helper T cell 1 (Th1)-related cytokines such as IFN-γ and IL-12, inhibits the differentiation of T cells into Th2 cells, and further affects the secretion of OVA-specific IgE and promotes the production of protective antibody IgG. The lung tissue analysis illustrates that DDA@OVA/PPy-PVA treatment achieves regular alveolar structures in the lumen and significantly relieved asthma symptoms. The findings indicate that iontophoresis patches provide multiple benefits, including drug-responsive release, efficient penetration, and advanced therapeutic efficacy. These attributes make iontophoresis patches a promising treatment option for allergic diseases.
研究领域:
生物医学工程
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药学
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免疫学
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过敏研究
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药物递送系统
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纳米技术
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材料科学
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呼吸系统疾病
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）