Science Advances
·
2018
·Vol. 4
·期 9
·
IF 11.511
Qilin Yu,Ying-Ming Zhang,Yao-Hua Liu,Xun Xu,Yu Liu
Supramolecular nanoassemblies that respond to multiple stimuli exhibit high therapeutic efficacy against malignant tumors. We report a new type of supramolecular nanofiber that integrates targeting peptide–coated magnetic nanoparticles with β-cyclodextrin–bearing polysaccharides in a complex held together by multivalent interactions. The nanofibers not only exhibited reversible photo-triggered association and disassociation depending on irradiation wavelength but also underwent magnetic field–controlled directional aggregation, even in the rather weak geomagnetic field. The nanofibers markedly suppressed invasion by and metastasis of cancer cells both in vitro and in vivo. Furthermore, compared with control mice, tumor-burdened mice treated with the nanofibers showed a lower rate of mortality from the metastatic spread of tumor cells. Our results suggest that these geomagnetism- and photo-controlled nanofibers may facilitate the rapid development of efficacious anticancer therapies.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
Biofabrication
·
2018
·Vol. 10
·期 3
·034102
·
IF 6.838
Zhichang Du,Shengli Mi,Xiaoman Yi,Yuanyuan Xu,Wei Sun
Tumour invasion into the surrounding stroma is a critical step in metastasis, and it is necessary to clarify the role of microenvironmental factors in tumour invasion. We present a microfluidic system that simulated and controlled multi-factors of the tumour microenvironment for three-dimensional (3D) assessment of tumour invasion into the stroma. The simultaneous, precise and continuous arrangement of two 3D matrices was visualised to observe the migration of cancer cell populations or single cells by transfecting cells with a fluorescent protein. A vascular endothelial layer was formed to simulate transendothelial transport of nutrients, and its endothelial barrier function was verified by the diffusion of 70 kDa fluorescein isothiocyanate (FITC)-Dextran in 3D matrices. Through high-throughput cell migration tracking observation and statistic evaluation, we clarified that cell density of the tumour directly determined its invasiveness. The results suggested that increased secretion of IL-6 among both cancer cells (MDA-MB-231) and noncancerous cells (MCF-10A or HDF-n) after co-culture contributes to cancer cell invasiveness, and this was verified by an IL-6 inhibitor assay. Finally, the drug efficacy of paclitaxel was reflected as changes in cancer cell migration ability, viability, and morphology. Together, our microfluidic devices could be a useful tool to study the mechanism of tumour invasion into the stroma and to screen anti-metastatic drugs.
研究领域:
生物医学工程
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肿瘤学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
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2020
·
IF 8.724
Yichuan Pang,Li Su,Yao Fu,Fan Jia,Chenxi Zhang,Xiankun Cao,Wenxin He,Xueqian Kong,Jiake Xu,Jie Zhao,An Qin
Breast cancer bone metastasis poses significant challenge for therapeutic strategies. Inside the metastatic environment, osteoclasts and tumor cells interact synergistically to promote cancer progression. In this study, the proprotein convertase furin is targeted due to its critical roles in both tumor cell invasion and osteoclast function. Importantly, the furin inhibitor is specifically delivered by bone targeting superparamagnetic iron oxide (SPIO) nanoparticles. Our in vitro and in vivo data demonstrate that this system can effectively inhibit both osteoclastic bone resorption and breast cancer invastion, leading to alleviated osteolysis. Therefore, the bone targeting & furin inhibition nanoparticle system is a promising therapeutic and diagnostic strategy for breast cancer bone metastasis.
研究领域:
肿瘤学
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纳米技术
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生物材料
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癌症转移
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Ningning Guo,Yi Zhou,Tiantian Wang,Mengting Lin,Jiejian Chen,Zhentao Zhang,Xincheng Zhong,Yiying Lu,Qiyao Yang,Donghang Xu,Jianqing Gao,Min Han
Metastasis is the primary cause of death for most cancer patients, in which tumor-associated macrophages (TAMs) are involved through several mechanisms. While hitherto there is still a lack of study on exclusive elimination of TAMs to inhibit metastasis due to the difficulties in specific targeting of TAMs, we construct an extra- and intracellular stepwise-responsive delivery system p-(aminomethyl)benzoic acid (PAMB)/doxorubicin (DOX) to achieve specific TAM depletion for the first time, thereby preventing tumor metastasis. Once accumulated into the tumor, PAMB/DOX would stepwise responsively (hypoxia and reactive oxygen species (ROS) responsively) disintegrate to expose the TAM-targeting ligand and release DOX sequentially, which depletes TAMs effectively in vivo. Owing to the inhibition of extracellular matrix (ECM) degradation, neovascularization, and tumor invasion contributed by TAM depletion, lung metastasis was successfully inhibited. Furthermore, PAMB/DOX showed efficient inhibition against tumor growth as well as spontaneous metastasis formation when combined with additional chemotherapy, representing a safe and efficient nanoplatform to modulate the adverse tumor microenvironment via TAM elimination.
研究领域:
癌症研究
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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
ONCOLOGY REPORTS
·
2023
·Vol. 51
·期 1
·1-13
·
IF 4.2
Gongjie Ye,Linglan Tu,Zhuduo Li,Xiangyu Li,Xiaoliang Zheng,Yongfei Song
Synaptopodin 2 (SYNPO2) plays a pivotal role in regulating tumor growth, development and progression in bladder urothelial Carcinoma (BLCA). However, the precise biological functions and mechanisms of SYNPO2 in BLCA remain unclear. Based on TCGA database‑derived BLCA RNA sequencing data, survival analysis and prognosis analysis indicate that elevated SYNPO2 expression was associated with poor survival outcomes. Notably, exogenous SYNPO2 expression significantly promoted tumor invasion and migration by upregulating vimentin expression in BLCA cell lines. Enrichment analysis revealed the involvement of SYNPO2 in humoral immune responses and the PI3K/AKT signaling pathway. Moreover, increased SYNPO2 levels increased the sensitivity of BLCA to PI3K/AKT pathway‑targeted drugs while being resistant to conventional chemotherapy. In in vivo BLCA mouse models, SYNPO2 overexpression increased pulmonary metastasis of 5637 cells. High SYNPO2 expression led to increased infiltration of innate immune cells, particularly mast cells, in both nude mouse model and clinical BLCA samples. Furthermore, tumor immune dysfunction and exclusion score showed that patients with BLCA patients and high SYNPO2 expression exhibited worse clinical outcomes when treated with immune checkpoint inhibitors. Notably, in the IMvigor 210 cohort, SYNPO2 expression was significantly associated with the population of resting mast cells in BLCA tissue following PD1/PDL1 targeted therapy. In conclusion, SYNPO2 may be a promising prognostic factor in BLCA by modulating mast cell infiltration and exacerbating resistance to immune therapy and conventional chemotherapy.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 45
·2004851
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IF 16.836
Xilin Li,Funeng Xu,Yang He,Yan Li,Jianwen Hou,Guang Yang,Shaobing Zhou
The high incidence of postoperative recurrence and metastasis has a serious effect on survival in breast cancer patients. Moreover, it is still a great challenge to prevent the postoperative recurrence and metastasis through traditional implantable devices due to their inability to control multiple drug release. Herein, an implantable hierarchical structured ultrafine fiber device with a time-programmed drug release function for the local postoperative adjuvant chemotherapy of breast cancer is developed. The structure is obtained through a co-axial electrospinning technology by the formation of the periodically arranged chambers inside a fiber matrix. The Doxorubicin hydrochloride in these chambers is released rapidly, killing the residual tumor cells to prevent tumor recurrence; while the matrix metalloproteinases-2 (MMP-2) inhibitor disulfiram in the fiber matrix is released in a sustained manner, inhibiting tumor invasion to prevent its metastasis. The fiber device implanted in tumor-bearing mice after a surgical tumor reduction displays excellent therapeutic efficacy by preventing both recurrence and metastasis. The mechanism investigation of tumor invasion through the type-II collagen immunofluorescence analysis reveals that the decrease of the activity of MMP-2 plays a key role in this process.
研究领域:
肿瘤学
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生物医学工程
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药学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
ONCOLOGY REPORTS
·
2025
·Vol. 53
·期 3
·1-14
·
IF 3.9
Dongsheng Lv,Xu Han,Liang Hao,Zhimin Sun,Aobo Zhang,Jing Liu,Liang Liu,Liqiang Liu
Cysteine‑ and glycine‑rich protein 2 (CSRP2) are closely associated with tumor invasion and metastasis. CSRP2 is significantly upregulated in glioma tissues and is associated with the clinical stage of the tumor. Overexpression of CSRP2 in glioma cells promotes the proliferation and metastasis of cancer cells, whereas CSRP2 knockdown inhibits the biological functions of tumor cells. Transcriptome sequencing of CSRP2‑knockdown U251M cells revealed that silencing of CSRP2 inhibited the JAK‑STAT1 signaling pathway, and differentially expressed genes were significantly enriched in cell processes related to necroptosis. Experiments on necroptosis in glioma cells using flow cytometry, Hoechst 33342/PI dual staining and transmission electron microscopy indicated that CSRP2 overexpression inhibited necroptosis in glioma cells. Western blotting results showed that overexpression of CSRP2 activated the JAK‑STAT1 signaling pathway, while the addition of the pathway inhibitor ruxolitinib promoted the phosphorylation of necroptosis proteins RIPK1, RIPK3 and MLKL. Therefore, it was hypothesized that CSRP2 maintains JAK‑STAT1 activation by inhibiting the protein inhibitor of activated STAT1, which then inhibits the necrotizing apoptosis of glioma cells.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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神经肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Future Medicinal Chemistry
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2024
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IF 3.2
Haili Yang,Xiaoyang Zhang,Letian Xu,Yuting Zhou,Rui Ma,Hao Chen,Siqin Zhao,Munkhtsetseg Baatar,Lvyi Chen,Xukun Deng,Hongwei Gu,Xiaoming Wang
Aim: Lysosomal pH changes are associated with drug resistance, cell growth and invasion of tumors, but effective and specific real-time monitoring of lysosomal pH compounds for cancer therapy is lacking. Materials & methods: Here, based on the covalent linkage of the anticancer drug palbociclib and fluorescent dye fluorescein isothiocyanate (FITC), we designed and developed a novel palbociclib-derived multifunctional molecule (Pal-FITC) for lysosomal targeting and diagnostic therapeutic integration. Results & discussion: Pal-FITC fluoresces is 20-fold stronger than that of FITC and shows a linear response in the pH range of 4.0–8.2 (R2 = 0.9901). Pal-FITC blocks cells in G1 phase via Cyclin D-CDK4/6-Rb. Conclusion: Our study provides new strategies for tumor-targeted imaging and personalized therapy.
研究领域:
肿瘤学
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药物化学
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分子生物学
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诊疗一体化
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-17
·
IF 17.694
Wang Weili,Zheng Huizhen,Jiang Jun,Li Zhi,Jiang Dongpeng,Shi Xiangru,Wang Hui,Jiang Jie,Xie Qianqian,Gao Meng,Chu Jianhong,Cai Xiaoming,Xia Tian,Li Ruibin
While hypoxia promotes carcinogenesis, tumour aggressiveness, metastasis, and resistance to oncological treatments, the impacts of hyperoxia on tumours are rarely explored because providing a long-lasting oxygen supply in vivo is a major challenge. Herein, we construct micro oxygen factories, namely, photosynthesis microcapsules (PMCs), by encapsulation of acquired cyanobacteria and upconversion nanoparticles in alginate microcapsules. This system enables a long-lasting oxygen supply through the conversion of external radiation into red-wavelength emissions for photosynthesis in cyanobacteria. PMC treatment suppresses the NF-kB pathway, HIF-1α production and cancer cell proliferation. Hyperoxic microenvironment created by an in vivo PMC implant inhibits hepatocarcinoma growth and metastasis and has synergistic effects together with anti-PD-1 in breast cancer. The engineering oxygen factories offer potential for tumour biology studies in hyperoxic microenvironments and inspire the exploration of oncological treatments.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Siao Yang,Xiaoxiao Hu,Zhengze Yong,Qingqing Dou,Cuilu Quan,Hong-Bo Cheng,Mo Zhang,Jing Wang
Photoimmunotherapy represents an innovative approach to enhancing the efficiency of immunotherapy in cancer treatment. This approach involves the fusion of immunotherapy and phototherapy (encompassing techniques like photodynamic therapy (PDT) and photothermal therapy (PTT)). Boron-dipyrromethene (BODIPY) has the potential to trigger immunotherapy owing to its excellent PD and PT efficiency. However, the improvements in water solubility, bioavailability, PD/PT combined efficiency, and tumor tissue targeting of BODIPY require introduction of suitable carriers for potential practical application. Herein, a disulfide bond-based hollow mesoporous organosilica (HMON) with excellent biocompatibility and GSH-responsive degradation properties was used as a carrier to load a bithiophene Aza-BODIPY dye (B5), constructing a sample chemotherapy reagent-free B5@HMON nanoplatform achieving triple-synergistic photoimmunotherapy. HMON, involving disulfide bond , is utilized to improve water solubility, tumor tissue targeting, and PD efficiency by depleting GSH and enhancing host-guest interaction between B5 and HMO. The study reveals that HMON’s large specific surface area and porous properties significantly enhance the light collection and oxygen adsorption capacity. The HMON’s rich mesoporous structure and internal cavity achieved a loading rate of B5 at 11 %. It was found that the triple-synergistic nanoplatform triggered a stronger anti-tumor immune response, including tumor invasion, cytokine production, calreticulin translocation, and dendritic cell maturation, eliciting specific tumor-specific immunological responses in vivo and in vitro . The BALB/c mouse model with 4T1 tumors was used to assess tumor suppression efficiency in vivo , showing that almost all tumors in the B5@HMON group disappeared after 14 days. Such a simple chemotherapy reagent-free B5@HMON nanoplatform achieved triple-synergistic photoimmunotherapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）