CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Linlin Song,Zhihui Liu,Xiujing He,Tianyue Xu,Meixu Chen,Zihan Xu,Haina Zhao,Jiaojiao Suo,Hong Wang,Zhankun Yang,Shenglan You,Xiaoting Chen,Guang Yang,Jing Jing,Yulan Peng,Hubing Shi
Synchronizing therapy and diagnosis is an ideal mode for clinical treatment of localized disease, e.g., tumor. Here, we develop a diagnosis-therapy coupled sonodynamic nano delivery system ZSMT which is constructed with a TiO 2 embedding hollow Mn-MOF. Loaded with perfluorohexane, the ZSMT nanoparticle is not only capable for carrying ozone as a ROS donor but also endowed with double modes of imaging, namely ultrasound and magnetic resonance imaging. The TiO 2 -Mn-MOF can efficiently generate ROS by sonodynamic catalyzing ozone. Moreover, fluorescent tracer indicates the ZSMT particle can be internalized by tumor cells. With the stimulation of ultrasound, ozone carried ZSMT potently inhibits cell proliferation and promotes immunogenic cell death in vitro and in vivo by inducing a mitochondrial related cell death. Remarkably, combination of ultrasound-responsive ozone catalytic nano system and PD-1 blockade systematically suppresses the tumor growth by reprogramming the immune microenvironment. In conclusion, our sonodynamic nano system not only proves the principle of drug administration strategy on “treat-as-you-see” but also provides a combo regimen of improving PD-1 blockade with precision localized antigen boosting.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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医学影像
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癌症生物学
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高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
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2026
·Vol. 104
·期 1
·53
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IF 5
Luo Yichen,Han Yanhong,Nie Huilong,Feng Minghao,Wei Cuiting,Ma Xiuling,Li Kefeng,Zhang Zhuangzhuang,Wang Guangxue,Pan Wenjun,Li Xueyang,Yi Liutong,Wang De-Yun,Zeng Xian-Tao,Qiao Yongkang,Yan Yan,Lin Yujing
The sympathetic adrenergic nerves (SAN) play a significant role in the malignant transformation of breast cancer cells through the activity of norepinephrine (NE). However, the role of tyrosine hydroxylase (TH), a key enzyme of the NE synthesis, in the interaction between the SAN and triple-negative breast cancer (TNBC) cells has not been sufficiently explored, and whether TH can be a therapeutic target for TNBC has not been reported. TH expression in TNBC was examined by analyzing data from an online database and immunohistochemical analysis of our clinical samples. Cell proliferation and drug sensitivity were assessed upon coculture with fluorescently labeled cells using IncuCyte. Changes in the expression of DNA damage and apoptosis-associated proteins were assessed by western blotting. TH expression and NE synthesis in PC12 cells after their coculture with TNBC cells were measured by RT–qPCR, immunofluorescence, and ELISA. RNA sequencing was conducted on the cells before and after coculture. TH expression was relatively high in TNBC tumor tissues and closely associated with prognosis. SAN promoted TNBC cell proliferation through NE and reduced TNBC cell sensitivity to chemotherapeutic agents. Additionally, tumor cells induced TH expression in PC12 cells through nerve growth factor (NGF) secretion. Knocking down TH and using TH inhibitors effectively reversed the proliferation-promoting and drug sensitivity-reducing effects of SAN in TNBC cells. TH may be a central molecule in the positive feedback loop between TNBC cells and SAN. TH is a potential prognostic biomarker and can also serve as a therapeutic target for TNBC. Key messages
The overexpression of the sympathetic nerve biomarker tyrosine hydroxylase (TH) in triple-negative breast cancer (TNBC) is an indicator for clinical staging, prognosis, and targeted therapy.
There is a feedback loop where TH in nerves produces NE, worsening TNBC and reducing chemotherapy effectiveness. TNBC cell then increases TH expression, further boosting NE production. Furthermore, blocking the activity of TH could effectively inhibit this phenotype.
Graphical
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高影响因子
Materials Today Bio
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2026
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IF 11
Pan Zhang,Minglun Liu,Lei Huang,Zijie Zhao,Qianqian Zhang,Yunhao Li,Yuncong Chen,Lili Liang
Triple-negative breast cancer (TNBC) frequently exhibits profound chemoresistance and a highly immunosuppressive tumor microenvironment (TME), leading to suboptimal clinical outcomes with high risks of early recurrence and distant metastasis. Existing monotherapies remain inadequate in disrupting these therapeutic barriers. To overcome the aforementioned obstacles, we developed a spatiotemporally regulated organelle-targeted nanoplatform, IR820-GEM@MIL101 (IGM), Its design aims to achieve precise mitochondrial intervention and coordinate cGAS–STING-mediated immune activation. This design relies on EPR-mediated passive targeting to achieve preferential tumor accumulation, allowing IGM to accumulate specifically in tumor tissues and trigger a series of reactions in response to endogenous stimuli (acidic pH and elevated glutathione) in synergy with exogenous near-infrared laser activation, enabling controlled drug release. The platform efficiently eliminates tumor cells by inducing multiple modes of cell death, including pyroptosis, ferroptosis, and apoptosis, while simultaneously triggering immunogenic cell death (ICD) and activating the cGAS–STING pathway. This dual immunostimulatory strategy effectively converts “cold” tumors into “hot” tumors. In a bilateral tumor model, IGM treatment increased CD8 + T-cell infiltration in distal tumors by 94% and achieved a tumor inhibition rate of 92.7% in distant lesions. This work shifts the therapeutic focus from superficial multi-drug packaging to precise organelle-targeted intervention, providing a promising strategy for light-regulated combinatorial immunotherapy against aggressive malignancies.
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高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Siqi Geng,Baoru Fang,Ke Wang,Fang Wang,Yiqing Zhou,Yike Hou,M. Zubair Iqbal,Yanping Chen,Zhangsen Yu
Photothermal therapy (PTT) is a promising technology that can achieve the thermal ablation of tumors and induce immunogenic cell death (ICD). However, relying solely on the antitumor immune responses caused by PTT-induced ICD is insufficient to suppress tumor metastasis and recurrence effectively. Fortunately, multifunctional nanoformulation-based synergistic photothermal immunotherapy can eliminate primary and metastatic tumors and inhibit tumor recurrence for a long time. Herein, we select polydopamine (PDA) nanoparticles to serve as the carrier for our nanomedicine as well as a potent photothermal agent and modulator of macrophage polarization. PDA nanoparticles are loaded with the insoluble immune adjuvant Imiquimod (R837) to construct PDA(R837) nanoformulations. These straightforward yet highly effective nanoformulations demonstrate excellent performance, allowing for successful triple-negative breast cancer (TNBC) treatment through synergistic photothermal immunotherapy. Moreover, experimental results showed that PDA(R837) implementation of PTT is effective in the thermal ablation of primary tumors while causing ICD and releasing R837, further promoting dendritic cell (DC) maturation and activating the systemic antitumor immune response. Furthermore, PDA(R837) nanoformulations inhibit tumor metastasis and recurrence and achieve M1 phenotype macrophage polarization, achieving long-term and excellent antitumor efficacy. Therefore, the structurally simple PDA(R837) nanoformulations provide cancer treatment and have excellent clinical translational application prospects.
研究领域:
纳米技术
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癌症研究
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免疫治疗
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生物医学工程
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药学
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-17
·
IF 10.6
Chen Wenting,Hu Fangfang,Gao Qian,Zheng Caiyun,Bai Que,Liu Jinxi,Sun Na,Zhang Wenhui,Zhang Yanni,Dong Kai,Lu Tingli
Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.Graphical Abstract
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 19
·期 1
·375-383
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IF 1.448
Xiaowei Shen,Jiaqi Lei,Lei Du
The limited efficacy of chemotherapy with Taxol (TAX) and cisplatin (DDP) in triple‑negative breast cancer (TNBC) has prompted the investigation of combined therapies. Previous studies demonstrated that microRNA (miR)‑31‑5p is involved in various biological processes. In the present study, it was hypothesized that the overexpression of miR‑31‑5p may enhance the efficacy of chemotherapy. The expression levels of miR‑31‑5p in the TNBC cell lines MDA‑MB‑231 and MDA‑MB‑468 were measured using reverse transcription‑quantitative PCR following transfection with miR‑31‑5p mimic or inhibitor. A Cell Counting Kit‑8 and flow cytometry assays suggested that the overexpression of miR‑31‑5p inhibited cell proliferation and promoted apoptosis, and these effects were reversed by transfecting a miR‑31‑5p inhibitor into MDA‑MB‑231 and MDA‑MB‑468 cells. Furthermore, the overexpression of miR‑31‑5p increased the sensitivity of cells to chemotherapy, which exhibited an increase in apoptosis and in the expression level of Bax, and a decrease in the expression level of Bcl‑2. Chemotherapy resistance induced by miR‑31‑5p inhibitor could be reversed by inhibiting the AKT signaling pathway in MDA‑MB‑231 and MDA‑MB‑468 cells. In conclusion, the present preclinical results indicated that targeting miR‑31‑5p may enhance the efficacy of TAX‑ and DDP‑mediated chemotherapy in TNBC.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
BREAST CANCER RESEARCH
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2025
·Vol. 27
·期 1
·217
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IF 5.6
Wang Ding,Luo Shulei,Yu Rongji,Wen Doudou,Jiang Hao,Xu Keli,Di Xiaotang,Zhang Shubing
Background Triple negative breast cancer (TNBC), characterized by its aggressive clinical behavior and propensity for distant metastasis, presents critical challenges in therapeutic management. Emerging evidence implicates lipid metabolic reprogramming as a key facilitator of tumor progression and metastatic dissemination. However, the precise molecular mechanisms underlying lipid metabolic dysregulation in TNBC metastasis remain poorly characterized. Our work systematically elucidates the mechanistic role of ALDH3A2 in orchestrating lipid metabolic adaptations that drive breast cancer metastasis. Methods Transcriptomic analysis of clinical datasets identified metastasis-related metabolic regulators. Cellular migration/invasion assays and murine metastasis models were utilized to assess metastatic effects of ALDH3A2. Lipidomic profiling coupled with pathway analysis characterized metabolic alterations. Mechanistic studies integrated western blot analysis with lipid droplet quantification. Computational approaches including structure-based virtual screening and molecular docking simulations were employed for inhibitor discovery. Results ALDH3A2 was significantly upregulated in TNBC clinical specimens and showed significant association with adverse clinical outcomes. Functional validation confirmed that ALDH3A2 potentiates TNBC cell migration/invasion through epithelial-mesenchymal transition (EMT) activation. Metabolic profiling revealed ALDH3A2-driven lipid accumulation, evidenced by increased lipid droplet formation and elevated triglyceride levels. Specifically, arachidonic acid (AA) enrichment was observed in ALDH3A2-overexpressing cells, corresponding to enhanced glycerophospholipid metabolism. Mechanistic studies demonstrated that ALDH3A2-mediated AMP/ATP imbalance suppresses AMPK phosphorylation while activating mTOR/SREBP1 signaling. mTOR inhibition effectively attenuated ALDH3A2-induced lipid metabolic alterations. Importantly, oxaliplatin was identified as a potential therapeutic agent targeting ALDH3A2-mediated AA metabolism to suppress metastasis. Conclusions Our work establishes ALDH3A2 as a pivotal regulator of lipid metabolic reprogramming in TNBC metastasis, providing mechanistic insights into AA-mediated tumor progression. These findings position ALDH3A2 as a promising therapeutic target and prognostic biomarker for TNBC management.
研究领域:
肿瘤学
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癌症生物学
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分子生物学
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代谢学
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信号转导
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药理学
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PubMed
高影响因子
Theranostics
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2026
·Vol. 16
·期 13
·7571
·
IF 14.9
Linlin Song,Meixu Chen,Huiling Wang,Xin Wang,Tianyue Xu,Heqing Zhang,Shuwen Ran,Liwen Huang,Yingying Ma,Zhihui Liu,Zihan Xu,Yujie Zhao,Zichang Liu,Yong Luo,Xiujun Yu,Yulan Peng,Hubing Shi,Jing Jing,Xiujing He
Rationale Triple-negative breast cancer (TNBC) remains one of the most aggressive subtypes due to its poor immunogenicity and resistance to systemic therapies. Methods Here, we report a multifunctional NIR-II light-triggered theranostic nanoplatform, termed LQPO, that integrates liposome, Ti 3 C 2 quantum dots (QDs), perfluorohexane (PFH), and ozone to enable multimodal imaging-guided photo-gas synergistic therapy. The QDs, embedded within the liposomal bilayer, act as highly efficient NIR-II photothermal transducers, while the PFH core serves as a liquid-gas phase-change medium capable of dissolving and releasing ozone under localized heating. Results Upon NIR-II irradiation, LQPO produced strong photothermal and photoacoustic signals for real-time photoacoustic (PA) and contrast-enhanced ultrasound (CEUS) imaging, accompanied by vaporization of the PFH core and burst release of ozone. This spatiotemporally coordinated cascade induced potent oxidative stress and hyperthermia, synergistically driving GSDME-dependent pyroptosis and immunogenic cell death (ICD). The resulting “in situ vaccination” effect remodeled the tumor immune microenvironment and primed tumors for PD-1 blockade therapy. In vivo , NIR-II-activated LQPO achieved efficient tumor accumulation, strong PA/CEUS imaging contrast, and pronounced inhibition of both primary and abscopal tumors when combined with αPD-1 therapy. No significant systemic toxicity was observed, confirming its favorable biosafety. Conclusions Overall, this study establishes a single-laser-activated nanoplatform that unifies real-time multimodal imaging and photo-gas synergistic therapy, and converts localized treatment into a systemic antitumor immune response upon integration with checkpoint inhibition.
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高影响因子
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
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2024
·Vol. 67
·期 11
·384-391
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IF 0.9
Shuhua He,Lina Jia,Xiaobei Zheng,Yang Wang,Yuxia Liu,Lan Zhang
Programmed death-ligand 1 (PD-L1) expression is related to the efficacy and prognosis in triple-negative breast cancer. This study employed an indirect labeling method to synthesize [ 125 I]PI-Atezolizumab. The in vitro stability of [ 125 I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [ 125 I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a K d value comparable to that of Atezolizumab. This suggests that the labeling process did not compromise the affinity of the Atezolizumab to PD-L1. Subsequently, pharmacokinetic studies were conducted in normal mice and biodistribution experiments in tumor-bearing mice. A comparison of the biodistribution results between [ 125 I]PI-Atezolizumab and 125 I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [ 125 I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [ 125 I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.
研究领域:
肿瘤学
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分子影像学
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放射性药物
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癌症生物学
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高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2018
·Vol. 37
·期 1
·1-11
·
IF 6.217
Dai Xuanxuan,Yin Changtian,Zhang Yi,Guo Guilong,Zhao Chengguang,Wang Ouchen,Xiang Youqun,Zhang Xiaohua,Liang Guang
Background Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer. Patients with TNBC have poor clinical outcome as they are non-responsive to current targeted therapies. There is an urgent need to identify new therapeutic targets and develop more effective treatment options for TNBC patients. Osthole, a natural product from C. monnieri, has been shown to inhibit certain cancer cells. However, the mechanisms of action as well as its effect on TNBC cells are not currently known.Methods We investigated the effect of osthole in cultured TNBC cells as well as in a xenograft model of TNBC growth. We also used a high-throughput proteomics platform to identify the direct binding protein of osthole.Results We found that osthole inhibited the growth of a panel of TNBC cells and induced apoptosis in both cultured cells and TNBC xenografts. We used a high-throughput proteomics platform and identified signal transducer and activator of transcription 3 (STAT3) as a potential binding protein of osthole. We further show that osthole suppressed STAT3 in TNBC cells to inhibit growth and induce apoptosis. Overexpressing STAT3 in TNBC reduced the effectiveness of osthole treatment.Conclusion sThese results provide support for osthole as a potential new therapeutic agent for the management of TNBC. Moreover, our results indicate that STAT3 may be targeted for the development of novel anti-TNBC drugs.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
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2025
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IF 15.4
Wang Xiaolu,Wang Qianqian,Wang Hong,Cai Guodi,An Yana,Liu Peiqing,Zhou Huihao,Chen Hong-Wu,Ji Shufeng,Ye Jiantao,Wang Junjian
Clinical treatment options for triple-negative breast cancer (TNBC) are currently limited to chemotherapy because of a lack of effective therapeutic targets. Recent evidence suggests that long noncoding RNAs (lncRNAs) encode bioactive peptides or proteins, thereby playing noncanonical yet significant roles in regulating cellular processes. However, the potential of lncRNA-translated products in cancer progression remains largely unknown. In this study, we identified a previously undocumented small protein encoded by the lncRNA LINC02870 . This protein is localized at the endoplasmic reticulum (ER) and participates in ER stress, thus, we named it the endoplasmic reticulum stress protein (ERSP). ERSP was highly expressed in TNBC tissues, and elevated LINC02870 content was correlated with poor prognosis in TNBC patients. Loss of ERSP inhibited TNBC growth and metastasis both in vitro and in vivo. The pro-oncogenic effects of ERSP could be attributed to its selective activation of the IRE1α/XBP1s branch. ERSP enhances the unfolded protein response (UPR) by interacting with XBP1s, facilitating the nuclear accumulation of XBP1s, thereby promoting the expression of ER stress-related genes. These findings highlight the regulatory role of the lncRNA-encoded protein ERSP in ER stress and suggest that it is a potential therapeutic target for TNBC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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高影响因子
Toxicology Research
·
2024
·Vol. 13
·期 2
·
IF 2.2
Niu Junjie,Hu Jinyang,Wang Zhu
BackgroundTriple-negative breast cancer (TNBC) lacks effective therapeutic targets. Scutellaria barbata D.Don (SB) has been revealed to have anti-breast cancer (BC) effect, but the effect of SB extract in TNBC is still unclear. Herein, this research delves into the underlying mechanism.MethodsSB was extracted by solvent extraction, and the main components were identified using an Agilent 6,520 HPLC-Chip/Q-TOF (Chip/Q-TOF) MS system. In vitro cell experiments were conducted. The effects of SB extract alone, SB extract plus EGF, GSK alone, GSK plus Ezrin overexpression, or SB extract plus Ezrin overexpression on cell viability, invasion, migration, and apoptosis were examined by cell function experiments. The apoptosis- and RhoA/ROCK1 pathway-related protein levels were analyzed by western blot assay.ResultsMass spectrometry analysis exhibited that SB extract mainly contains long-chain fatty acids and ursolic acid. SB extract mitigated TNBC cell biological phenotypes, apoptosis- and RhoA/ROCK1 pathway-related marker expressions, which were reversed by EGF. The further results found that GSK obviously weakens TNBC cell biological behaviors, apoptosis- and RhoA/ROCK1 signaling-related protein levels, while oe-Ezrin treatment reverses the effect of GSK on TNBC cells. Moreover, SB extract regulated Ezrin-mediated function of TNBC cells by impeding the RhoA/ROCK1 pathway.ConclusionOur findings demonstrated that SB extract regulated Ezrin-mediated proliferation, migration, invasion, and apoptosis of TNBC cells via suppressing the RhoA /ROCK1 signaling. Our results offer the experimental foundation for further investigation of the anti-cancer role of SB in TNBC cells.HighlightsSB extract inhibits the biological phenotypes of TNBC cells.SB extract inhibits the biological behaviors of TNBC cells through the RhoA/ROCK1 pathway.SB extract modulates Ezrin-mediated TNBC cell proliferation, migration, invasion, and apoptosis via restraining the RhoA/ROCK1 signaling.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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高影响因子
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