Breast Cancer-Targets and Therapy
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2023
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IF 2.6
Mengqi Zhang,Shengxian Bao,Guanhua Qiu,Jingchen Liang,Qin Wang,Xiaoqi Zhu,Guchun Qin,Junjie Liu,Chang Zhao
Purpose In this experiment, we constructed a magnetic targeting nano-diagnosis and treatment platform of doxorubicin (DOX) combined with iron nanoparticles, and explored their application value and mechanism in the treatment of Triple Negative Breast Cancer (TNBC), as well as its new diagnosis and treatment mode in Magnetic Resonance Imaging (MRI).Patients and Methods Hollow mesoporous nanoparticles (HFON) were synthesized by solvothermal method, and loaded the drug DOX (DOX@HFON) to treat TNBC. The experiments in vivo and in vitro were carried out according to the characteristics of the materials. In vitro experiments, the killing effect of the drug on cells was verified by cell viability CCK8, ROS generation level, LPO evaluation and flow cytometry; the MRI effect and targeted anti-tumor therapy effect were studied by in vivo experiments; then the tumor tissue sections were detected by Ki-67, CD31, ROS, LPO and TUNEL immunofluorescence detection; H&E staining and blood biochemical tests were used to evaluate the biosafety of the materials.Results Through a series of characterization tests, it is confirmed that the nano-materials prepared in this experiment have positive drug loading properties. MDA-MB-231 cells had great phagocytic ability to DOX@HFON under Confocal Laser Scanning Microscope (CLSM). Experiments in vitro confirmed that DOX and Fe were released and concentrated in cells, and a large number of ROS production and induction of LPO were detected by DCFH-DA and C11-BODIPY probes in cells. Apoptosis experiments further confirmed that DOX@HFON induced apoptosis, autophagy and ferroptosis. In the vivo experiment, the anti-tumor therapy effect of MAGNET@DOX@HFON group was the most significant, and in MRI also proved that the drug had great tendency and imaging ability in tumor tissue.Conclusion The new magnetic targeting nano-diagnosis and treatment platform prepared in this experiment is expected to become a new treatment model for TNBC.
研究领域:
癌症研究
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纳米技术
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分子生物学
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成像技术
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药理学
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DOI
高影响因子
Cancers
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2024
·Vol. 16
·期 5
·885
·
IF 4.5
Qianrui Huang,Mengling Wu,Yamin Pu,Junyou Zhou,Yiqian Zhang,Ru Li,Yong Xia,Yiwen Zhang,Yimei Ma
Simple SummaryThe objective of drug repurposing is to discover novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a commonly prescribed antidepressant, has demonstrated promising anticancer properties in experimental studies. Nevertheless, its precise role and mechanisms of action in triple-negative breast cancer (TNBC) remain incompletely elucidated. Our research findings propose that PX may impact TNBC by modulating critical molecular pathways, providing significant implications for enhancing chemosensitivity and identifying potential therapeutic synergies in clinical practice. These findings provide a basis for the creation of individualized treatment plans and the identification of the most effective therapeutic interventions to enhance treatment precision and effectiveness in patients with TNBC.AbstractThe strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous. This study aimed to examine the impact of PX on TNBC cells in vitro as both a standalone treatment and in conjunction with other pharmaceutical agents. Cell viability was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, apoptosis was assessed through flow cytometry, and the effects on signaling pathways were analyzed using RNA sequencing and Western blot techniques. Furthermore, a subcutaneous tumor model was utilized to assess the in vivo efficacy of combination therapy on tumor growth. The results of our study suggest that PX may activate the Ca2+-dependent mitochondria-mediated intrinsic apoptosis pathway in TNBC by potentially influencing the PI3K/AKT/mTOR pathway as well as by inducing cytoprotective autophagy. Additionally, the combination of PX and chemotherapeutic agents demonstrated moderate inhibitory effects on 4T1 tumor growth in an in vivo model. These findings indicate that PX may exert its effects on TNBC through modulation of critical molecular pathways, offering important implications for improving chemosensitivity and identifying potential therapeutic combinations for clinical use.
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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癌症治疗
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
·
IF 19
Biao-Qi Chen,Yu-Hong Shi,Yang Zhang,Da-Gui Zhang,Xiao-Chang Lu,Qin-Xi Xu,Yu-Jing Pan,Ranjith Kumar Kankala,Shi-Bin Wang,Ai-Zheng Chen
Triple-negative breast cancer (TNBC) is a highly aggressive subtype lacking specific molecular targets, rendering conventional therapies ineffective. Key obstacles in treatment include elevated intracellular glutathione (GSH), poor drug penetration, and an immunosuppressive tumor microenvironment. Herein, a four-in-one Janus-type near-infrared (NIR)-driven nanomotor is employed, composed of copper selenide (Cu 2-x Se) asymmetrically coated with disulfide-bridged periodic mesoporous organosilica (PMO) and loaded with doxorubicin (DOX), termed C&P-DOX. Upon NIR irradiation, Cu 2-x Se generates localized hyperthermia, propelling the nanomotor into deep tumor regions due to their asymmetrical structure. After internalization, high GSH triggers disulfide cleavage, promoting GSH depletion, disrupting redox homeostasis, and achieving controlled DOX release. The uniform distribution and effective release of DOX throughout the tumor enhance cytotoxic effects, inducing significant tumor cell apoptosis. In addition, the synergistic mild photothermal therapy and chemotherapy induce immunogenic cell death, releasing damage-associated molecular patterns and tumor-associated antigens that promote dendritic cell maturation and T-cell activation. This process transforms the tumor immunosuppressive microenvironment into an immunogenic environment, enhancing cytotoxic T lymphocyte infiltration and synergizing with PD-L1 antibody therapy to amplify immune responses. The four-pronged C&P-DOX nanomotor effectively penetrates deep tumors, depletes GSH, combines tumor treatment, and enhances immunotherapy outcomes, integrating active synergistic chemo-photothermal-immune therapy for improved TNBC treatment.
研究领域:
纳米医学
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肿瘤学
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药学
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免疫治疗
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Materials Today Advances
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2022
·
IF 9.918
Jiahao Liang,Chao Wang,Jialong Fan,Qian Xie,Zhenlong Yu,Bin Liu,Yan Tian,Jing Ning,Lei Feng,Wei Wang,Xiaochi Ma
Triple-negative breast cancer (TNBC) metastasis is the cause of nearly 90% of breast cancer treatment failures as the side effects of clinical drugs and insufficient efficacy of single-modality therapy. Shikonin (SHK) is a naphthoquinone natural product from the herbal medicine Lithospermum erythrorhizon ., which is widely used for cancer therapy as one kind of Chinese medicine for its significant anti-tumor, anti-metastatic, and anti-inflammatory effects. However, passive targeting of SHK to tumor location in vivo and long-term high dose administration is likely to decrease heart rate and induce drug resistance, which accordingly results in therapeutic failure. Thus, we designed a biomimetic SHK-loading nano-system (Hybrid [email protected] / [email protected] @SHK nanoparticles, HMGPHS NPs) to achieve controlled release and reduced SHK dosage. The prolonged circulation time and higher targeting of the HMGPHS NPs allowed less drug leakage systemically with increased drug concentration at the tumor sites compared to naked ICG/ [email protected] @SHK (GPHS) NPs. Moreover, SHK could down-regulate the expression of COX-2, IL-6, and TNF-α to reduce the photothermal therapy-induced inflammatory response and improve the tumor microenvironment (TME), enabling HMGPHS NPs to significantly inhibit the growth and metastasis of TNBC. We propose that the combination of high efficacy, prolonged circulation, and high targeting of HMGPHS NPs could facilitate the conversion of SHK to clinical application for the effective treatment of TNBC.
研究领域:
肿瘤学
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药剂学
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纳米技术
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癌症治疗
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产品关联
DOI
高影响因子
BIOMATERIALS
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2024
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IF 12.8
Pingting Ye,Chunhui Wang,Yixuan Wen,Kang Fang,Qi Li,Xin Zhang,Jingxian Yang,Ruihao Li,Mengyao Chen,Xiaohan Tong,Shuo Shi,Chunyan Dong
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer due to poor immunogenicity and limited immune cell infiltration, efficient therapeutics are still deficiency. Ferroptosis, a reactive oxygen species (ROS)-reliant cell death, can enhance cellular immunogenicity and then active immune system. To sustain a long-term “hot” tumour immune microenvironment (TIME), an immune-modulator is indispensable. Metformin (MET), a commonly used oral drug for type 2 diabetes, has played a vital role in fostering an immunostimulatory environment. Herein, we confirm the TIME can be remodeled by MET and further promotes ferroptosis via upregulating cellular concentration of l -Glutamine. In light of this, we have design a self-assembled MET-loaded Fe 3+ -doped polydopamine nanoparticle (Fe-PDA-MET NP) that can disorder the cellular redox homeostasis and induce robust ferroptosis under 808 nm irradiation, resulting in a strong immune response. Based on the function of MET, there is a marked increase in the infiltration of activated CD8 + T cells and NK cells, which subsequently augments ferroptosis to a greater extent. Taken together, Fe-PDA-MET NPs activate a ferroptotic positive-feedback loop for effectively control TNBC progression, which offers a promising therapeutic modality to enhance the immunogenicity and reshape the TIME.
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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癌症生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yuao Feng,Zeliang Wu,Hui Liu,Rong Xu
Triple-negative breast cancer (TNBC) presents a formidable challenge due to its poorest prognosis and limited array of treatment options available. Photodynamic therapy (PDT) has emerged as a potent therapeutic modality to generate intratumoral toxic reactive oxygen species (ROS) in combating refractory triple-negative breast cancer (TNBC). However, its therapeutic efficacy is compromised due to insufficient tumor accumulation and therapeutic resistance. Herein, an “all-in-one” tumor-therapeutic nanomedicine named HA@IR780@KU55933@BSA (HIKB) which integrated photosensitizer IR780 with ATM kinase inhibitor KU55933 was designed to facilitate drug delivery and target specific pathways involved in tumor PDT treatment resistance. Co-delivery of IR780 and KU55933 exacerbated intracellular ROS production, mitochondrial dysfunction and DNA damage to form a potent anti-TNBC therapeutic cyclical feedback loop and then induced pyroptosis and apoptosis of TNBC cells by activating the Caspase3/GSDME signaling pathway and regulating apoptosis-related protein expression, respectively. In vivo evaluations in the TNBC orthotopic xenograft mouse model demonstrated that the designed HIKB NPs could accumulate in tumor tissues and exert synergistic therapeutic effects. Altogether, this study described a self-assembling strategy for constructing an all-in-one nanomedicine that effectively integrates multiple therapeutic modalities to provide a comprehensive and systemic approach to tumor suppression.
研究领域:
肿瘤学
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治疗学
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纳米技术
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癌症生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 5
·1876-1894
·
IF 6.6
Guoyun Wan,Xuheng Chen,Jiayu Chen,Ruiling Gou,Haijiao Wang,Shuhao Liu,Mingyang Zhang,Hongli Chen,Dan Wang,Qiqing Zhang
Recurrence and metastasis are the main reasons for failure in the treatment of triple-negative breast cancer (TNBC). Phototherapy, one of the most well-known potent cancer treatment models is highlighted by ablating primitive tumors with immunogenic cell death (ICD) and is associated with endoplasmic reticulum (ER) stress to elicit long-lasting anti-tumor immunity. However, the provoked inflammatory response after phototherapy will stimulate angiogenesis, which provides nutrition for tumor recurrence. Here, an ER-targeted nanoplatform was constructed based on hollow mesoporous Cu2−XS (HMCu2−XS) nanoparticles to suppress recurrence and metastasis of TNBC by combining photo-ablation and microenvironment remodeling. Profiting from the metal ion coordination and large hollow space, HMCu2−XS can be easily modified with p-toluenesulfonamide for ER-targeting and quantitatively loaded celecoxib (CXB) as a vascular inhibitor, thus obtaining ER-HMCu2−XS/CXB. ER-HMCu2−XS showed great photothermal and photodynamic efficiency for ablating 4T1 tumors and inducing ICD under NIR-II laser irradiation. Compared with non-ER-targeted nanosystems, the ER-targeted nanosystem elicited stronger ICDs and recruited more immune cells. Moreover, the thermal-responsively released CXB successfully inhibited angiogenesis after photothermal therapy. The data showed that the ER-HMCu2−XS/CXB mediated the triplicate therapeutic effect of photo-ablation, immune response activation, and vascular suppression effectively, preventing the recurrence and metastasis of TNBC. In conclusion, this work provides a synergistic strategy to enhance therapeutic outcomes in TNBC.
研究领域:
癌症治疗
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纳米技术
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免疫学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Breast Cancer-Targets and Therapy
·
2026
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IF 3.6
Peng Chen,Jiapeng Xu,Yulong Liang,Jinghui Mu,Wenjing Feng,Jiaming Liu,Bolun Li
Objective To investigate the biological function of SLC2A9 in triple-negative breast cancer (TNBC) and its molecular mechanism of influencing TNBC cells by regulating uric acid (UA) metabolism.Methods Bioinformatics analysis was performed to screen genes intersecting TNBC and UA metabolism pathways. TNBC cell lines were cultured in vitro, followed by the establishment of SLC2A9 overexpression and knockdown models. Subsequently, the levels of intracellular and extracellular UA were quantified. Cell proliferation, apoptosis, migration, and invasion capabilities were assessed using CCK-8, plate cloning, flow cytometry apoptosis analysis, scratch assay, and Transwell assays. Western blot analysis evaluated the expression of apoptosis-related proteins and UA metabolism proteins.Results SLC2A9 was significantly downregulated in TNBC tissues and most cell lines. SLC2A9 overexpression inhibited TNBC cell proliferation, migration, and invasion while promoting apoptosis. It also increased extracellular UA secretion and reduced intracellular UA accumulation. Conversely, SLC2A9 knockdown or probenecid treatment reversed these phenotypes. SLC2A9 exerts its effects by upregulating XDH, downregulating ABCG2, and modulating mitochondrial apoptosis pathway protein expression.Conclusion SLC2A9 regulates the malignant phenotype of TNBC by altering the levels of UA inside and outside the cell. Its anticancer activity depends on UA transport function, making it a promising prognostic biomarker and novel metabolic therapeutic target for TNBC.
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Xiaojing Zhang,Yansong Chen,Jingwei Tang,Chen Chen,Yanfeng Sun,Hao Zhang,Mengxiang Qiao,Gongsheng Jin,Xianfu Liu
Combination chemotherapy is an effective approach for triple-negative breast cancer (TNBC) therapy, especially when drugs are administered at specific optimal ratios. However, at present, strategies involving precise and controllable ratios based on effective loading and release of drugs are unavailable. Herein, we designed and synthesized a glutathione (GSH)--responsive heterotrimeric prodrug and formulated it with an amphiphilic polymer to obtain nanoparticles (DSSC2 NPs) for precise synergistic chemotherapy of TNBC. The heterotrimeric prodrug was prepared using docetaxel (DTX) and curcumin (CUR) at the optimal synergistic ratio of 1: 2. DTX and CUR were covalently conjugated by disulfide linkers. Compared with control NPs, DSSC2 NPs had quantitative/ratiometric drug loading, high drug co-loading capacity, better colloidal stability, and less premature drug leakage. After systemic administration, DSSC2 NPs selectively accumulated in tumor tissues and released the encapsulated drugs triggered by high levels of GSH in cancer cells. In vitro and in vivo experiments validated that DSSC2 NPs released DTX and CUR at the predefined ratio and had a highly synergistic therapeutic effect on tumor suppression in TNBC, which can be attributed to ratiometric drug delivery and synchronous drug activation. Altogether, the heterotrimeric prodrug delivery system developed in this study represents an effective and novel approach for combination chemotherapy.
研究领域:
肿瘤学
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药剂学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Linlin Song,Dan Zheng,Jinshun Xu,Tianyue Xu,Zhihui Liu,Huan Zhang,Yi Li,Yulan Peng,Hubing Shi
Despite revolutionary achievements have been made in clinical cancer therapy, the immune checkpoint blockade regimen still presents limited efficacy on tumors lack of neoantigens exposure. Here, we designed and synthesized an on-demand microwave-controlled ozone release nanosystem to specifically generate reactive oxygen species in tumor mass. By taking advantage of iRGD modification, the synthesized nanosystem can be specifically enriched in the tumor microenvironment and subsequently internalized by tumor cells. Triggered by the low-power microwave, ozone was released from the nanocarriers and inhibited tumor cell growth in vitro and in vivo . Molecular mechanism investigation further unraveled that the released-ozone induced cytolytic cell death through the rapid generation of reactive oxygen species such as hydroxyl radical. The tumor-specific neoantigen derived from this immunogenic cell death promoted cytotoxic T-lymphocytes infiltration, which provided a fundament for immune checkpoint blockade therapy. In the triple-negative breast cancer animal model, tumor-specific delivery of ozone significantly improved the systematical anti-tumor efficacy of the PD-1 blockade antibody. Notably, tumor-locally confined microwave-controlled release avoided systematic toxicity in the tested animals. Collectively, our nanosystem provides a novel controllable strategy for promoting immune checkpoint blockade therapy, especially in tumor types deficient in infiltrated T-lymphocytes.
研究领域:
癌症治疗
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纳米技术
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免疫疗法
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
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
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2026
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IF 7.8
Leilei Zhang,Haoheng Bai,Weiqi Sun,Luqi Wang,Minyan Duan,Qianying Liu,Chao Zhou,Xueyang Fang,Tao Zhang
Triple-negative breast cancer (TNBC) treatment with traditional phototherapeutics generally suffers from short light penetration depth and limitations of the hypoxic tumor microenvironment. Developing effective therapeutic modalities tailored to TNBC’s features remains highly desirable yet challenging. Herein, we propose a near-infrared dual windows (NIR-II) photoacoustic (PA) cavitation-based strategy to amplify oxidative stress and induce metabolic disruption in TNBC cells, achieving effective tumor suppression. With a fabricated nanoagent (DTG), we integrated the oxygen-independent therapeutic effects of photomechanical damage, cavitation-promoted oxidative damage and glucose oxidase (GOx)-mediated glucose depletion. Specifically, under NIR-II pulsed laser (PL) irradiation, PA cavitation generates collapsing bubbles and shock waves, causing mechanical injury to tumor cells. Meanwhile, GOx depletes intratumoral glucose, blocking glycolysis, reducing adenosine triphosphate (ATP) production, and generating hydrogen peroxide (H2O2) that would be further converted into more toxic hydroxyl radicals (•OH) by the photocavitation to suppress the tumors effectively. In addition, the strong NIR-II PA signal produced from the DTG facilitates high-resolution deep-tissue imaging to provide precise therapeutic guidance. Thus, these findings establish the multimodal strategy as a potent candidate for TNBC management.
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产品关联
DOI
PubMed
高影响因子
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