COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2026
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IF 5.4
Caifen Yu,Zhenzhen Chen,Jin Liu,Xiaoyu Shi,Wenbin Xie,Lingjun Zeng,Minxin Zhang,Shenghang Zhang,Aiwen Huang,Shuiliang Wang
A novel anti-solvent ultrasonication method to fabricate luteolin-loaded BSA NPs. • Noncovalent hydrophobic interactions to fabricate aptamer-functionalized Lut-BSA NPs. • Multifunctional nanoplatform integrates natural compounds with nano and aptamer. • Superior tumor inhibition and biosafety highlight clinical translational potential. Luteolin (Lut) is a promising active component derived from traditional Chinese medicine for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, its clinical translation is substantially hindered by intrinsic physicochemical limitations: poor aqueous solubility and lack of tumor-selective biodistribution. So, we fabricated luteolin-loaded bovine serum albumin (BSA) nanoparticles (Lut-BSA NPs) via a modified anti-solvent ultrasonication method, in which BSA functions simultaneously as a biocompatible drug carrier and stabilizing agent. Then, HApt, the HER2-targeted aptamer, was conjugated to the surface of Lut-BSA NPs to generate the targeted nanoplatform HApt-Lut-BSA NPs, which act as a HER2 navigator to enable precise tumor targeting. HApt-Lut-BSA NPs demonstrated a high encapsulation efficiency of 87.64 ± 1.02% and a loading content of 3.87 ± 0.03%. In vitro release studies indicated that HApt-Lut-BSA NPs exhibited favorable release under acidic conditions, facilitating Lut accumulation in tumors. Cellular uptake assays and MTT analysis demonstrated that HApt-Lut-BSA NPs exhibited excellent targeting and cytotoxicity in vitro . In vivo fluorescence imaging confirmed superior accumulation of HApt-Lut-BSA NPs in SK-BR-3 tumor-bearing NPSG mice, while pharmacodynamic evaluation showed pronounced tumor growth inhibition and satisfactory in vivo safety. Collectively, this multifunctional nanoplatform that uniquely integrates a natural compound with nanotechnology and aptamer technology, not only markedly improves druggability and tumor-targeted delivery efficiency, but also offers a broadly applicable paradigm for the delivery of poorly water-soluble therapeutics and may promote the development of clinically translatable targeted drugs. Download: Download high-res image (228KB) Download: Download full-size image
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高影响因子
ANALYTICAL CHEMISTRY
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2019
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IF 6.35
Zongwen Wang,Qian Chen,Yingying Zhong,Xinhui Yu,Yongning Wu,FengFu Fu
Many studies have demonstrated that the extracellular domain of human epidermal growth factor receptor 2 (HER2 ECD) level in serum can act as a breast cancer biomarker and serve as a monitoring neoadjuvant therapy of breast cancer. In this study, we developed a sensitive ascorbic acid (AA)-mediated AuNBPs (gold nanobipyramids) growth method with NADH (reduced nicotinamide adenine dinucleotide I) assistance, and we further fabricated a high-resolution multicolor immunosensor for sensitive visual detection of HER2 ECD in serum by using AuNBPs as signal and antibody as recognition probe. The NADH-assisted AA-mediated method effectively suppressed color formation in the blank and greatly improved the sensitivity of mediating AuNBPs growth, allowing us to use a low concentration of AA to mediate AuNBPs growth to generate more colorful and clearer color changes. The proposed multicolor immunosensor has higher resolution and more color changes corresponding to HER2 ECD concentrations. It can be used to detect as low as 0.5 ng/mL of HER2 ECD by bare eye observation and 0.05 ng/mL of HER2 ECD by UV–visible spectrophotometry. Using the immunosensor, we have successfully detected HER2 ECD in human serum with a recovery of 94%–96% and an RSD (n = 5) < 5%. The results obtained with our immunosensor were consistent with those obtained with ELISA, verifying the immunosensor has good accuracy. The immunosensor exhibited a vivid multicolor change, has low visual detection limit, excellent specificity and reproducibility, and robust resistance to matrix. All the above features makes our immunosensor a promising assay for the early diagnosis of HER2-dependent breast cancers in clinical diagnosis.
研究领域:
生物化学
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医学诊断
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纳米技术
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PubMed
高影响因子
PLoS One
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2017
·Vol. 12
·期 8
·e0183941
·
IF 2.806
Wen Che,Yun Bao,Feng Tang
Background
Resistance to human epidermal growth factor receptor-2 (HER2)-targeted therapies is common, and results in treatment failure and new tumor progression. C35 is over-expressed in many invasive breast cancer endogenously, and functions as an oncogene in breast cancer cell lines.
Methods
The current study aims to investigate effects of C35 on cell viability and migration of HER2-positive breast tumor cells and explore possible mechanisms. The protein expression of C35 in BT-474 breast ductal carcinoma cells was interfered by siRNAs. MTT assay was utilized to detect the viability of BT474 breast ductal carcinoma cells after transfection. The migration of BT474 breast ductal carcinoma cells was examined by cell wound scratch assay.
Results
In addition, the protein expression of C35, HER2, AKT and p-AKT in breast ductal carcinoma cells were detected by Western Blot. The protein expression of C35 was weaker in siRNA1 and siRNA2 groups compared with the control group. The relative expression ratio of C35 to β-actin decreased significantly in siRNA2 and siRNA1 groups. When C35 expression was interfered by siRNA1 and siRNA2 for 48 h, the viability of BT474 breast ductal carcinoma cells decreased compared with the control group. In addition, the migration of breast ductal carcinoma cells decreased when C35 expression was interfered by siRNA1 for 24 h, and interfered by siRNA1 and siRNA2 for 48 h.
研究领域:
肿瘤学
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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
International Journal of Analytical Chemistry
·
2026
·Vol. 2026
·期 1
·3877339
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IF 2.8
Feifei Liu,Jing Li,Wenna Jiang,Jing Pang,Shuo An,Yue Shi,Li Ren
Human epidermal growth factor receptor 2 (HER2) is a critical biomarker for targeted therapy of gastric cancer. Tissue-based HER2 testing via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) remains the clinical gold standard, while serum HER2 represents a potential complementary circulating biomarker for disease monitoring. However, conventional serum HER2 assays often suffer from limited sensitivity. Herein, we develop a highly sensitive fluorescence assay for serum HER2 detection using nonlinear hybridization chain reaction (NHCR) coupled with a HER2-specific aptamer (HB5). Unlike linear hybridization chain reaction (HCR), NHCR enables branching-mediated exponential amplification, in which each trigger initiates multiple independent HCR cascades, leading to nonlinear signal growth. The method exhibited a good linear relationship ( R 2 = 0.993) in the HER2 concentration range of 0.5–90 ng·mL −1 , with a detection limit as low as 38 pg·mL −1 . The sensor demonstrated excellent specificity for HER2, good reproducibility, and reliable stability. Clinical serum sample detection results indicated that the method was highly correlated with the clinically commonly used chemiluminescence immunoassay (CLIA), with spiked recoveries ranging from 95.4% to 109.6%. The NHCR-based fluorescent detection strategy established in this study provides a new tool for accurate and noninvasive detection of serum HER2, featuring simple operation and controllable cost.
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高影响因子
Acta Pharmaceutica Sinica B
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2026
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IF 14.6
Yuxuan Yang,Yun Xing,Jialing Zhang,Yujie Dai,Letao Ma,Teng Yang,Yuanzheng Li,Yuxuan Li,Jingfang Zhang,Yucheng Wang,Youmin Ying,Chuanfei Yu,Peng Guo,Qing Wei,Meng Li,Juxian Wang,Lan Wang
The clinical application of trastuzumab deruxtecan (T-DXd), a transformative HER2-targeted antibody‒drug conjugate (ADC), is limited by interstitial lung disease (ILD), a severe adverse event associated with alveolar macrophage (AM)-mediated uptake and Fc γ receptor (Fc γ R) engagement. To mitigate this toxicity while preserving anti-tumor efficacy, we explored Fc-engineering strategies aimed at reducing Fc γ R binding and immune activation. Using enzymatic deglycosylation and site-specific mutations (N297A and LALAPG), we generated Fc-engineered trastuzumab variants and incorporated them into T-DXd. Our findings demonstrate that these Fc-engineered ADCs significantly reduce macrophage internalization and lung accumulation without compromising HER2 antigen recognition or tumor cell uptake. In preclinical models, Fc-engineered ADCs reduced ILD incidence, attenuated neutrophil infiltration, and decreased activation of inflammatory pathways. Importantly, they maintain anti-tumor potency. Transcriptomic analysis further reveals that Fc-engineered ADCs suppress antigen processing and presentation pathways implicated in ILD pathogenesis. These results suggest that Fc engineering represents a promising strategy for mitigating ADC-induced pulmonary toxicity, offering a safer alternative for HER2-targeted therapies. Fc-engineered trastuzumab ADCs with reduced Fc γ R affinity decrease macrophage uptake and ILD incidence while preserving HER2 binding and antitumor efficacy. Download: Download high-res image (250KB) Download: Download full-size image
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高影响因子
ANALYTICAL CHEMISTRY
·
2026
·Vol. 98
·期 33
·24226-24236
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IF 7.3
Ding Haiying,Liu Xiaoyin,Guo Bingxue,Qiu Yueping,Wu Jingyu,Wang Yunxiao,Cui Baiqi,Fang Luo,Zhang Fenni
Antibody–drug conjugates (ADCs) rely on specific
recognition
of tumor-associated membrane receptors to achieve targeted intracellular
drug delivery, yet in situ characterization of their
interaction dynamics remains limited. Here, we develop a single-cell
plasmonic imaging platform to quantitatively resolve the interaction
between the membrane human epidermal growth factor receptor 2 (HER2)
and HER2-targeted therapeutics. This label-free approach enables continuous
monitoring of the molecular interaction process, allowing real-time
extraction of detailed binding kinetics. Using this platform, we systematically
compare the binding behaviors of the HER2-targeting antibody trastuzumab
(Herceptin) and clinically relevant ADCs (T-DM1 and T-DXd), revealing
distinct kinetic signatures associated with the drug conjugation.
Analysis across cell lines with different HER2 expressions reveals
that increased receptor density does not necessarily enhance binding
stability, suggesting a potential trade-off between receptor availability
and effective interaction dynamics. To further evaluate the potential
capability of tracking membrane-associated dynamics, polystyrene nanoparticle
probes were employed to validate real-time imaging of endocytosis
dynamics, distinguishing uptake behavior in live versus fixed cells.This
work establishes cell-based plasmonic imaging as a quantitative and
mechanistic approach for evaluating ADC-receptor interactions in situ , offering valuable insights for rational ADC design
and precision therapeutic optimization.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Shi-Jie Hao,Ya-Xuan Zhu,Fu-Gen Wu
Although nanocarriers have been widely applied in the delivery of anticancer drugs , many commercialized anticancer nanodrug systems still suffer from the problem of being easily trapped by lysosomes, which severely limits the drug delivery efficiency of a nanodrug system. Meanwhile, in drug-resistant tumors, the efflux of anticancer therapeutic drugs via the drug efflux transporters on the plasma membrane of cancer cells can significantly decrease the intracellular drug concentration and lead to the failure of the drug treatment. Here, we developed a small-molecule tyrosine kinase inhibitor (TKI)- and doxorubicin (Dox, a common anticancer drug)-loaded membrane fusion liposome (MFL) (termed [email protected] ) to achieve tumor cell membrane fusion-mediated drug delivery and enhanced chemotherapy of drug-resistant tumor. MFL could deliver drugs in a membrane fusion manner, circumventing the capture by lysosomes. Lapatinib, as the TKI doped in the MFL, could inhibit the efflux of Dox by ATP-binding cassette transporters (ABC transporters), further promoting the intracellular Dox accumulation. As a result, Dox achieved effective killing of drug-resistant tumors under the dual effect of MFL and lapatinib. To the best of our knowledge, it is the first example that employs membrane fusion-mediated TKI delivery for achieving tumor chemosensitization with good biosafety. This work presents an efficient and easily achievable strategy for treating drug-resistant tumors, which may hold promise for clinical applications.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
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高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Xiaoming Su,Yangcenzi Xie,Xinyu Liu,Mingyang Chen,Chao Zheng,Hong Zhong,Ming Li
Exosomes (exos) widely existing in body fluids show great potential for noninvasive cancer diagnosis. Quantitative analysis of exos is traditionally performed by targeting specific exosomal surface proteins, but it is often imprecise due to the common expression of exosomal proteins and subtle expression differences between different cancer subtypes. Herein, we report quantitative surface-enhanced Raman spectroscopy (SERS) of serum exos through a combination of a paper-based lateral flow strip (LFS) biosensor with multivariate spectral unmixing analysis rather than simply quantifying exosomal proteins. Our SERS-LFS biosensor enables absolute quantification of two different serum exos with a limit of detection down to ∼106 particles/mL for both exos. We further exemplify the application of this strategy in quantitative dual-plex detection of serum exos from breast cancer patients. We find that human epidermal growth factor receptor 2+ (HER2+) and luminal A breast cancer patients undergoing no surgery are enriched in serum exos derived from SKBR-3 cells and MCF-7 cells (denoted as SKBR and MCF exos), respectively. The surgical treatment of these breast cancer patients accompanies an obvious decrease of either SKBR or MCF exos in the serum. These results suggest the great potential of the combination of the SERS-LFS biosensor and multivariate spectral unmixing for breast cancer subtyping and therapeutic surveillance with the powerful quantitative capability of exos in clinical samples.
研究领域:
生物医学工程
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癌症诊断
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分子生物学
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高影响因子
MOLECULAR PHARMACEUTICS
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2021
·
IF 4.939
Mingyang Li,Jicheng Dong,Fang Cheng,Chunmei Li,Huanan Wang,Tao Sun,Wei He,Qing Wang
For active targeting nanodrug delivery systems conjugated with antibodies, both lack of control of the antibody at the molecular level and protein corona formation remarkably decreases targeting efficacy. Herein, we designed a series of silica nanoparticles toward HER2-positive breast cancer cells, with an anti-HER2 Fab-6His density ranging from 50 to 180 molecules per nanoparticle. Through the site-directed immobilization method we developed, the antigen-binding domain of anti-HER2 Fab was mostly accessible to the HER2 receptor. Both polyethylene glycol (PEG) chains and a high density of Fab were shown to suppress protein corona formation and macrophage uptake. The dependency of targeting efficacy and cytotoxicity on Fab density was shown using a series of breast cancer cell lines with different levels of the HER2 expression. The high density of Fab stimulates quick responses from HER2-positive cells. Combined with PEG chains, conjugated antibodies with a well-controlled orientation and density significantly improves delivery performance and sheds light on the design and preparation of an improved active targeting nanodrug delivery system.
研究领域:
纳米技术
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癌症研究
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药物递送系统
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分子生物学
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PubMed
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-18
·
IF 4.122
Du Jing,Li Xiao-Yu,Hu He,Xu Li,Yang Shi-Ping,Li Feng-Hua
Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C 3 F 8 )-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro , single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo , US imaging signal in the murine breast cancer model was significantly higher ( P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo . This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.
研究领域:
医学影像
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肿瘤学
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药剂学
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生物医学工程
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高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Shanshan Wei,Wanjun Ma,Yuanying Yang,Taoli Sun,Chuanhao Jiang,Jian Liu,Bikui Zhang,Wenqun Li
Trastuzumab (Tra), the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2), is commonly used alongside doxorubicin (Dox) as a combination therapy in HER2-positive breast cancer. Unfortunately, this leads to a more severe cardiotoxicity than Dox alone. NLRP3 inflammasome is known to be involved in Dox-induced cardiotoxicity and multiple cardiovascular diseases. However, whether the NLRP3 inflammasome contributes to the synergistic cardiotoxicity of Tra has not been elucidated. In this study, primary neonatal rat cardiomyocyte (PNRC), H9c2 cells and mice were treated with Dox (15 mg/kg in mice or 1 μM in cardiomyocyte) or Tra (15.75 mg/kg in mice or 1 μM in cardiomyocyte), or Dox combined Tra as cardiotoxicity models to investigate this question. Our results demonstrated that Tra significantly potentiated Dox-induced cardiomyocyte apoptosis and cardiac dysfunction. These were accompanied by the increased expressions of NLRP3 inflammasome components (NLRP3, ASC and cleaved caspase-1), the secretion of IL-β and the pronounced production of ROS . Inhibiting the activation of NLRP3 inflammasome by NLRP3 silencing significantly reduced cell apoptosis and ROS production in Dox combined Tra-treated PNRC. Compared with the wild type mice, the systolic dysfunction , myocardial hypertrophy , cardiomyocyte apoptosis and oxidative stress induced by Dox combined Tra were alleviated in NLRP3 gene knockout mice . Our data revealed that the co-activation of NLRP3 inflammasome by Tra promoted the inflammation, oxidative stress and cardiomyocytes apoptosis in Dox combined Tra-induced cardiotoxicity model both in vivo and in vitro . Our results suggest that NLRP3 inhibition is a promising cardioprotective strategy in Dox/Tra combination therapy.
研究领域:
肿瘤学
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心脏病学
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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
International Journal of Nanomedicine
·
2023
·
IF 8
Dongdong Zheng,Caifeng Wan,Hong Yang,Li Xu,Qi Dong,Chengrun Du,Jing Du,Fenghua Li
Purpose The treatment of breast cancer is often ineffective due to the protection of the tumor microenvironment and the low immunogenicity of tumor cells, leading to a poor therapeutic effect. In this study, we designed a nano-theranostic platform for these obstacles: a photothermal effect mediated by a gold shell could remodel the tumor microenvironment by decreasing cancer-associated fibroblasts (CAFs) and promote the release of doxorubicin (DOX) from nanoparticles. In addition, it could realize photoacoustic (PA)/MRI dual-model imaging for diagnose breast cancer and targeted identification of Her2-positive breast cancer.Methods Her2-DOX-superparamagnetic iron oxide nanoparticles (SPIOs)@Poly (D, L-lactide-co-glycolide) acid (PLGA)@Au nanoparticles (Her2-DSG NPs) were prepared based on a single emulsion oil-in-water (O/W) solvent evaporation method, gold seed growing method, and carbon diimide method. The size distribution, morphology, PA/MRI imaging, drug loading capacity, and drug release were investigated. Cytotoxicity, antitumor effect, cellular uptake, immunogenic cell death (ICD) effect, and targeted performance on human Her2-positive BT474 cell line were investigated in vitro. BT474/Adr cells were constructed and the antitumor effect of NPs on it was evaluated in vitro. Moreover, chemical-photothermal therapy effect, PA/MRI dual-model imaging, ICD effect induced by NPs, and tumor microenvironment remodeling in human BT474 breast cancer nude mice model were also investigated.Results Nanoparticles were spherical, uniform in size and covered with a gold shell. NPs had a photothermal effect, and can realize photothermal-controlled drug release in vitro. Chemical-photothermal therapy had a good antitumor effect on BT474/Adr cells and on BT474 cells in vitro. The targeting evaluation in vitro showed that Her2-DSG NPs could actively target and identify Her2-positive tumor cells. The PA/MRI imaging was successfully validated in vitro/vivo. Similarly, NPs could enhance the ICD effect in vitro/vivo, which could activate an immune response. Immunofluorescence results also proved that photothermal effect could decrease CAFs to remodel the tumor microenvironment and enhance the accessibility of NPs to tumor cells. According to the toxicity results, targeted drug delivery combined with photothermal-responsive drug release proved that NPs had good biosafety in vivo. Chemical-photothermal therapy of Her2-targeted NPs has a good antitumor effect in the BT474 nude mice model.Conclusion Our study showed that chemical-photothermal therapy combined with tumor microenvironment remodeling and immune activation based on the Her2-DSG NPs we developed are very promising for Her2-positive breast cancer.
研究领域:
纳米技术
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癌症生物学
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诊疗学
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生物医学工程
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药学
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医学影像
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PubMed
高影响因子
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