查找使用阿拉丁产品的科研文献

Classification of breast cancer by a gold nanoparticle based multicolor fluorescent aptasensor

Yunyun Wu,Yuqing Feng,Xi Li

Breast cancer has seriously threatened women health in the world. Breast cancer classification may provide accurate molecular diagnosis information of the disease and prediction of tumor behavior to facilitate oncologic decision making. Here, we designed a dual-aptamers functionalized gold nanoprobe (DA-GNP) for classification of breast cancer based on Förster resonance energy transfer (FRET). The fluorescent labelled ER and HER2 (typical biomarker for breast cancer classification) specific aptamers are attached to gold nanoparticles’ (GNPs) surface and fluorescence is quenched ultimately. The breast cancer subtype specific fluorescence will be recovered while the fluorescent labelled aptamer is bound to the biomarker protein, which are potentially useful for quantitative classification of different subtypes of breast cancer.

A ddPCR platform based on a microfluidic chip with a dual-function flow-focusing structure for sample-to-result DNA quantification analysis

xiaoliang zhang,Shun Wang,Jinxian Wang,Xiaojie Sun,Jinbing Xue,Zhenya Wang,Tianhang Yang,Liangfei Weng,Bidou Wang,Gangyin Luo

Droplet digital PCR (ddPCR) is a powerful method for absolute nucleic acid quantification with high precision and accuracy. However, complicated operational steps have hampered the use and diffusion of ddPCR. Therefore, an automated, easy-to-use, low-sample-consumption, and portable ddPCR platform is urgently needed. This paper proposes a microfluidic ddPCR platform based on a microfluidic chip that can realize the sample-to-result function by switching the rotary valve, achieving the dual function of the flow-focusing structure for droplet generation and readout. Sample, generation oil, and analysis oil were pre-added to the reservoirs. Droplets were generated due to focusing flow, and after passing through the integrated temporary storage bin in the rotary valve, the droplets and oil subsequently entered the collecting tube, improving the droplet-to-oil volume ratio for enhanced thermal cycle performance. Droplets with an average diameter of 107.44 μm and a CV of 2.38% were generated using our chip under the optimal pressures. High-performance thermal cycling was achieved through improvements of the droplet-to-oil volume ratio of the sample, the integrated heating lid, the pure copper heating base, and the temperature-controlling algorithm. Gradient quantification experiments were conducted for the HER2 and CEP17 genes extracted from breast cancer cells, yielding strong linear correlations with R2 values of 0.9996 for FAM and 0.9989 for CY5. Moreover, pronounced linearity was obtained between the detected concentrations of HER2 and CEP17, indicated by a slope of 1.0091 and an R² of 0.9997, signifying consistent HER2:CEP17 ratios across various sample dilutions. The outcomes of the quantitative analysis, encompassing the dynamic range and the consistency of the HER2:CEP17 ratio using our ddPCR platform, meet the standards required for breast cancer assessment and therapy. Our ddPCR platform is automated, portable, and capable of stable droplet generation, high-efficiency amplification, realization of the sample-to-result function based on dual-function flow-focusing structure, and accuracy absolute quantification, underscoring its significant potential for ddPCR analysis in clinical diagnostics.

Trastuzumab-Conjugated Nanoliposomes for Targeted Capecitabine Delivery to Suppress HER2-Positive Breast Tumor: Efficacy Analysis in NOD SCID Mice Xenografts

Shubhashree Das,Bhabani Sankar Satapathy,Mohamed Rahamathulla,Yahya Alhamhoom,Sovan Pattanaik,Saurabh Chawla,Gurudutta Pattnaik,Diptirani Rath,Mohammed Muqtader Ahmed,Ismail Pasha

Introduction Treatment of advanced breast cancer has proven to be difficult. Routine chemotherapy has limitations due to unavoidable and dreaded adverse effects during and after treatment, necessitating the development of tailored therapies. Capecitabine is a commonly used anticancer drug that comes in tablet form for oral administration. However, high doses and frequent administration-related toxicities limit its efficacy in HER2-positive breast cancer patients.Methods The current work seeks to target capecitabine using experimental nanoliposomes coupled to trastuzumab (TZ) (HER2-targeting monoclonal antibody) and assess anticancer activity in a NOD SCID mice xenograft model of breast cancer. Experimental capecitabine-loaded trastuzumab-nanoliposomes (TZ-CNLs) were developed by a previously reported method. FESEM, AFM, TEM, zeta potential, and drug release studies were used to characterize TZ-CNLs. In vivo effectiveness of CNLs/TZ-CNLs was carried out in experimental mice and compared with the free capecitabine-treated group. Hematological, biochemical, and histopathological analyses of experimental CNLs/TZ-CNLs were conducted across different treatment groups compared with the control.Results Experimental TZ-CNLs were spherical, smooth, and uniformly distributed, with an average size (198.6 nm), a zeta potential (−27.91 mV), and a drug loading (9.6±0.51%). The AFM indicated that TZ conjugation had no effect on texture. TZ-CNLs released 81.5 ± 3.05% capecitabine after 96 h, compared to CNLs/free capecitabine. After 12 days of treatment, TZ-CNLs significantly reduced tumor development (97.91 ± 3.0 mm3) compared to unconjugated CNLs/free capecitabine in NOD SCID mice xenografts. The enhanced antitumor activity observed with TZ-CNLs is consistent with HER2-targeted delivery mediated by TZ conjugation. Furthermore, TZ-CNL-treated animals maintained a healthier body-weight profile compared with free capecitabine and CNL-treated groups, suggesting improved treatment tolerability and reduced systemic toxicity. Plasma pharmacokinetic analysis indicated that administration of TZ-CNL-3 resulted in greater systemic availability of capecitabine, as well as prolonged mean residence time and increased volume of distribution, compared to free capecitabine and CNL-3. The study depicted an overall improvement in key biochemical parameters toward normal in animals treated with TZ-CNLs.Conclusion Overall, the promising preclinical outcomes, including tumor inhibition, improved hematologic and biochemical safety indices, and maintenance of organ histopathology, support the need for future preclinical investigations to determine whether TZ-CNLs may have application in HER2-positive breast cancer therapy.

Multifunctional superparamagnetic nanoparticles conjugated with fluorescein-labeled designed ankyrin repeat protein as an efficient HER2-targeted probe in breast cancer

Dong-Li Li,Jian-Er Tan,Ying Tian,Shun Huang,Peng-Hui Sun,Meng Wang,Yan-Jiang Han,Hong-Sheng Li,Hu-Bing Wu,Xing-Mei Zhang,Yi-Kai Xu,Quan-Shi Wang

Based on the discordance of human epidermal growth factor receptor-2 (HER2) expression between primary and metastatic/recurrent breast cancer, HER2 molecular imaging, which had potential to systemically assess and dynamically monitor HER2 expression, might improve the selection of patients for anti-HER2 therapy. In this study, designed ankyrin repeat protein (DARPin) G3, a novel binding protein with picomolar affinity for HER2, was used and multifunctional superparamagnetic nanoparticles modified with fluorescein-5-maleimide-labeled DARPin G3 (SPIO-G3-5MF) were developed for HER2 imaging. Our results showed that SPIO-G3-5MF nanoparticles, which possessed uniform size of about 100 nm, favorable dispersity and low cytotoxicity, could selectively bind to HER2-positive breast cancer cells even in the presence of trastuzumab. Biodistribution assay demonstrated that abundant accumulation and long retention of SPIO-G3-5MF were observed in HER2-positive transplantation breast tumors although a portion of SPIO-G3-5MF nanoparticles were unavoidably captured by liver and spleen. Further MR imaging revealed that SPIO-G3-5MF could selectively image HER2-positive transplantation breast tumors, yielding remarkable T 2 signal reduction (50.33 ± 2.90% at 6 h and 47.29 ± 9.36% at 24 h). Our study suggested that SPIO-G3-5MF might be a promising MR molecular probe for diagnosing and monitoring HER2 expression state of breast cancer in the future.

Her2-Functionalized Gold-Nanoshelled Magnetic Hybrid Nanoparticles: a Theranostic Agent for Dual-Modal Imaging and Photothermal Therapy of Breast Cancer

Dong Qi,Yang Hong,Wan Caifeng,Zheng Dongdong,Zhou Zhiguo,Xie Shaowei,Xu Li,Du Jing,Li Fenghua

Targeted theranostic platform that integrates multi-modal imaging and therapeutic function is emerging as a promising strategy for earlier detection and precise treatment of cancer. Herein, we designed targeted gold-nanoshelled poly (lactic-co-glycolic acid) (PLGA) magnetic hybrid nanoparticles carrying anti-human epidermal growth factor receptor 2 (Her2) antibodies (Her2-GPH NPs) for dual-modal ultrasound (US)/magnetic resonance (MR) imaging and photothermal therapy of breast cancer. The agent was fabricated by coating gold nanoshell around PLGA nanoparticles co-loaded with perfluorooctyl bromide (PFOB) and superparamagnetic iron oxide nanoparticles (SPIOs), followed by conjugating with anti-Her2 antibodies. Cell-targeting studies demonstrated receptor-mediated specific binding of the agent to Her2-positive human breast cancer SKBR3 cells, and its binding rate was significantly higher than that of Her2-negative cells (P < 0.001). In vitro, the agent had capabilities for contrast-enhanced US imaging as well as T2-weighted MR imaging with a relatively high relaxivity (r2 = 441.47 mM−1 s−1). Furthermore, the Her2 functionalization of the agent prominently enhanced the US/MR molecular imaging effect of targeted cells by cell-specific binding. Live/dead cell assay and targeted photothermal cytotoxicity experiments confirmed that Her2-GPH NPs could serve as effective photoabsorbers to specifically induce SKBR3 cell death upon near-infrared laser irradiation. In summary, Her2-GPH NPs were demonstrated to be novel targeted theranostic agents with great potential to facilitate early non-invasive diagnosis and adjuvant therapy of breast cancer.

Artificial Intelligence-Aided Multiple Tumor Detection Method Based on Immunohistochemistry-Enhanced Dark-Field Imaging

Lin Fan,Ting Huang,Doudou Lou,Zengzhou Peng,Yongqi He,Xinyu Zhang,Ning Gu,Yu Zhang

The immunohistochemical method serves as one of the most practical tools in clinical cancer detection and thus has great application value to overcome the existing limits of the conventional method and further improve the detecting efficiency and sensitivity. This study employed 3,3′-diaminobenzidine (DAB), a conventional color indicator for immunohistochemistry, as a novel high-sensitive scattering reagent to provide a multidimensional image signal varying with the overexpression rate of tumor markers. Based on the scattering properties of DAB aggregates, an efficient and robust artificial intelligence-aided immunohistochemical method based on dark-field imaging has been established, with improvement in both the imaging quality and interpretation efficiency in comparison with the conventional manual-operated immunohistochemical method. Referencing the diagnosis from three independent pathologists, this method succeeded in detecting HER2 overexpressed breast tumors with a sensitivity of 95.2% and a specificity of 100.0%; meanwhile, it was found to be applicable for non-small-cell lung tumors and malignant lymphoma as well. As demonstrated, this study provided an effective and reliable means for making diagnostic suggestions, which exhibited great potential in multiple tumor pathological detection at low cost.

A “signal-on” photoelectrochemical sensor for human epidermal growth factor receptor 2 detection based on Y6/CdS organic–inorganic heterojunction

Luo Jiarong,Luo Junjun,Deng Lei,Yang Minghui,Chen Xiang

A “signal-on” photoelectrochemical (PEC) immunosensor was successfully constructed for determination of human epidermal growth factor receptor 2 (HER2) based on organic–inorganic heterojunction Y6/CdS as photoactive material. Compared with single organic semiconductor, Y6, Y6/CdS exhibited higher photoelectric conversion efficiency due to the formation of heterojunction. In the presence of HER2, sandwich immune structure was formed between HER2 aptamer and anti-HER2 antibody (Ab) by specific recognition. The polydopamine (PDA) nanoparticles were used for signal amplification to enhance photocurrent intensity as PDA can act as electron donor to eliminate holes and promote electron–hole pairs separation. The developed PEC sensor displayed a wide detection range of 5–1000 pg mL −1 and a low detection limit of 2.2 pg mL −1 for HER2 (S/N = 3). The sensor was successfully used for the detection of HER2 in serum with recoveries between 94.8 and 104% and relative standard deviations (RSDs) in the range of 1.2–4.3%. Furthermore, the designed immunosensor possessed good stability, selectivity, and reproducibility, which can find potential clinical applications for disease diagnosis. Graphical abstract A “signal-on” photoelectrochemical sensor was reported for human epidermal growth factor receptor 2 detection based on Y6/CdS organic–inorganic heterojunction

Fabrication of Bioconjugates Clacked Chitosan-Coated SN-38 Liposomal Nanoparticles: Improved Precise Chemotherapy Efficacy in Lung Cancer Cells and Its Apoptosis

Xiaojun Zhang,Wei Sun,Changting Liu

Employing an active targeting method with monoclonal antibodies for chemotherapeutics-loaded nanocarriers represents a promising option to enhance the specific drug delivery and alleviate the detrimental effects of chemotherapeutic agents. Targeted delivery to the human epidermal growth factor receptor-2 (HER2), which is overexpressed in HER2+ lung cancerous cells, can be accomplished by conjugating nanoparticles with a monoclonal antibody (anti-HER2). We developed trastuzumab (TZ)-conjugated chitosan iodoacetamide (CsIA)-coated liposomal nanoparticles carrying SN-38 (TZ-SN-CsIA LNPs) as a lung-targeted delivery. CsIA was used to develop trastuzumab-clacked nanoparticles (TZ LNPs). The structure, physicochemical characteristics, SN-38 encapsulation, SN-38 release, and anticancer properties of the LNPs were established. The TZ LNPs were spherical, measuring around 77 nm in diameter, and exhibited a positive zeta potential; upon drug incorporation, the diameter of the TZ LNPs enlarged. A sustained, 24-h SN-38 release from the nanocarriers was accomplished. TZ LNPs demonstrated substantial cellular accumulation and markedly enhanced anticancer efficacy against HER2+ Calu-3 lung adenocarcinoma cancer cells compared to the drug solution and unconjugated LNPs. Consequently, TZ-SN-CsIA LNPs may be a potential nanocarrier for HER2+ lung cancer.

Targeted Fe-doped silica nanoparticles as a novel ultrasound–magnetic resonance dual-mode imaging contrast agent for HER2-positive breast cancer

Xiaoyu Li,Shujun Xia,Wei Zhou,Ri Ji,Weiwei Zhan

A dual-targeted hyaluronic acid-gold nanorod platform with triple-stimuli responsiveness for photodynamic/photothermal therapy of breast cancer

Weijun Xu,Junmin Qian,Guanghui Hou,Yaping Wang,Jinlei Wang,Tiantian Sun,Lijie Ji,Aili Suo,Yu Yao

Multi-stimuli-responsive theranostic nanoplatform integrating functions of both imaging and multimodal therapeutics holds great promise for improving diagnosis and therapeutic efficacy. In this study, we reported a pH, glutathione (GSH) and hyaluronidase (HAase) triple-responsive nanoplatform for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT dual-therapy against HER2-overexpressed breast cancer. The nanoplatform was fabricated by functionalizing gold nanorods (GNRs) with hyaluronic acid (HA) bearing pendant hydrazide and thiol groups via Au-S bonds, and subsequently chemically conjugating 5-aminolevulinic acid (ALA), Cy7.5 and anti-HER2 antibody onto HA moiety for PDT , fluorescence imaging and active targeting, respectively. The resulting versatile nanoplatform GNR-HA −ALA/Cy7.5 -HER2 had uniform sizes, favorable dispersibility, as well as pH, GSH and HAase triple-responsive drug release manner. In vitro studies demonstrated that HER2 and CD44 receptor-mediated dual-targeting strategy could significantly enhance the cellular uptake of GNR-HA −ALA/Cy7.5 -HER2. Under near-infrared (NIR) irradiation, MCF-7 cells could efficiently generate reactive oxygen species (ROS) and heat, and be more efficiently killed by a combination of PDT and PTT as compared with individual therapy. Pharmacokinetic and biodistribution studies showed that the nanoplatform possessed a circulation half-life of 1.9 h and could be specifically delivered to tumor tissues with an accumulation ratio of 12.8%. Upon the fluorescence imaging-guided PDT/PTT treatments, the tumors were completely eliminated without obvious side effects. The results suggest that the GNR-HA −ALA/Cy7.5 -HER2 holds great potential for breast cancer therapy. Statement of significance A combination of photodynamic therapy (PDT) and photothermal therapy (PTT) is emerging as a promising cancer treatment strategy. However, its therapeutic efficacy is compromised by the nonspecific delivery and unintended release of photo-responsive agents. Herein, we developed a multifunctional theranostic nanoplatform GNR-HA −ALA/Cy7.5 -HER2 with pH, glutathione and hyaluronidase triple-responsive drug release for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT therapy against breast cancer. We demonstrated that HER2 and CD44 receptors-mediated dual-targeting strategy significantly enhanced the cellular uptake of GNR-HA −ALA/Cy7.5 -HER2. We also demonstrated that the combined PDT/PTT treatment had significantly superior antitumor effect than PDT or PTT alone both in vitro and in vivo . Therefore, GNR-HA −ALA/Cy7.5 -HER2 could serve as a promising nanoplatform for HER2-positive breast cancer therapy.

AKT inhibitor MK-2206 sensitizes breast cancer cells to MLN4924, a first-in-class NEDD8-activating enzyme (NAE) inhibitor

Xiaoyu Chen,Danrui Cui,Yanli Bi,Jianfeng Shu,Xiufang Xiong,Yongchao Zhao

Breast cancer is a common type of cancer among female cancer patients and the main cause of cancer-related deaths. During the last decades, targeted therapies for breast cancer have been rapidly developing. Among them, MLN4924, a first-in-class NEDD8-activating enzyme (NAE) inhibitor, has performed antitumor activity by inactivating the cullin-RING ligases and causing the accumulation of their substrates to induce apoptosis in a number of studies. In this study, we found that MLN4924 activates the AKT pathway in both HER2-positive and triple-negative breast cancer (TNBC) cell lines. Given that AKT signaling is responsible for tumor progression and drug resistance in some types of cancers, we hypothesized that the AKT inhibitor may synergistically enhance the tumor suppression capability in breast cancer by MLN4924. To demonstrate the sensitizing effect, MK-2206 was chosen as the adjuvant treatment, and cell growth, migration and apoptosis were detected. The results showed that MLN4924 treatment inhibited cell growth and migration and induced apoptosis in both SK-BR3 and MDA-MB231 breast cancer cell lines. More importantly, the combined treatment of MLN4924 and MK-2206 indeed caused stronger cytotoxicity and inhibition of migration and a much higher induction of apoptosis compared with MLN4924 treatment alone. Our study provides the proof-of-concept evidence for strategic drug combination of MLN4924 with an AKT inhibitor for maximal killing of breast cancer cells via the enhancement of apoptosis.

Dose-sparing effect of lapatinib co-administered with a high-fat enteral nutrition emulsion: preclinical pharmacokinetic study

Junfeng Zhu,Gaoqi Xu,Dihong Yang,Yu Song,Yinghui Tong,Sisi Kong,Haiying Ding,Luo Fang

Background Lapatinib is an oral small-molecule tyrosine kinase inhibitor indicated for advanced or metastatic HER2-positive breast cancer. In order to reduce the treatment cost, a high-fat enteral nutrition emulsion TPF-T was selected as a dose-sparing agent for lapatinib-based therapies. This study aimed to investigate the effect of TPF-T on lapatinib pharmacokinetics. Methods First, a simple and rapid liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to quantitatively evaluate lapatinib in rabbit plasma. The method was fully validated according to the China Pharmacopoeia 2020 guidance. Rabbits and rats were chosen as the animal models due to their low and high bile flows, respectively. The proposed LC–MS/MS method was applied to pharmacokinetic studies of lapatinib, with or without TPF-T, in rabbit and rat plasma. Results The LC–MS/MS method revealed high sensitivity and excellent efficiency. In the rabbit model, co-administration with TPF-T resulted in a 32.2% increase in lapatinib exposure. In the rat model, TPF-T had minimal influence on the lapatinib exposure. In both models, TPF-T was observed to significantly elevate lapatinib concentration in the absorption phase. Conclusion Co-administration with TPF-T had a moderate effect on increasing exposure to lapatinib. Dose sparing using a high-fat liquid diet is potentially feasible for lapatinib-based therapies.