查找使用阿拉丁产品的科研文献

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.

A dual-aptamer-based biosensor for specific detection of breast cancer biomarker HER2 via flower-like nanozymes and DNA nanostructures

Dan Ou,Duanping Sun,Xiangan Lin,Zhixian Liang,Yongsheng Zhong,Zuanguang Chen

Developing highly sensitive and selective detection strategies for biomarkers is beneficial for fundamental research and disease diagnosis. Herein, we constructed a sandwich-type electrochemical aptasensor to detect the breast cancer cell biomarker Human Epidermal Growth Factor Receptor 2 (HER2). The aptasensor was a combination of tetrahedral DNA nanostructures (TDNs)–aptamer as recognition probes and flower-like nanozymes/horseradish peroxidase (HRP) as signal nanoprobes. In the process of assembling the biosensor, the TDN–aptamer 1 as a bio-recognition element was immobilized on the gold electrode (GE) surface for capturing the biomarker HER2. The nanozyme Mn3O4 was decorated by Pd@Pt nanozymes which were linked by the aptamer 2 and natural enzyme HRP. The designed Mn3O4/Pd@Pt/HRP nanoprobe (nanoprobe 1) was used to amplify the biosensor signal via catalyzing the oxidation of hydroquinone (HQ) with hydrogen peroxide (H2O2). After binding HER2, an aptamer–protein–nanoprobe sandwich system was fabricated on the GE surface. Lastly, a Pd@Pt/HRP/complementary DNA (cDNA) nanoprobe (nanoprobe 2) was added on the surface of nanoprobe 1 through DNA hybridization of aptamer 2 and cDNA to form a dendritic DNA nanostructure to further amplify the signal significantly. The results indicate that the aptasensor shows a broad linear response from 0.1 to 100.0 ng mL−1 and the low detection limit is 0.08 ng mL−1. The designed approach holds great potential for the construction of various aptasensors for the effective and convenient detection of different biomarkers.

Enzyme-free and label-free detection of HER2 in human serum based on Ag+-released hybridization chain reaction signal amplification

Huaze Shao,Hong Yan,Qing Tang,Shiquan Zheng,Hanren Chen,Lihong Liu

The overexpression of human epidermal growth factor receptor 2 (HER2) has been linked to aggressive breast cancer and worse clinical outcomes. However, accurately measuring HER2 remains challenging, due to its low serum content. Herein, we developed a novel method for HER2 detection in serum by the combination of aptamer with C-Ag + -C structure, Ag + -released hybridization chain reaction (Ag + -HCR) and coprecipitation of Ag + and gold nanoparticles (AuNPs) in the solution including Eosin Y (EY) and AgI colloids. Following the aptamer bound to HER2, signal amplification occurred through the release of numerous Ag + by Ag + -HCR. This process subsequently induced AuNPs aggregation on the surface of AgI colloids, resulting in reduced fluorescence intensity of EY in the supernatant. The reduced value of EY fluorescence intensity in the supernatant was proportional to the level of HER2. Under optimized reaction conditions, a wide detection range was obtained between 0.09 and 9000 pg/mL with a limit of detection of 11.7 fg/mL in diluted human serum, and 96 serum samples in a 96-well plate could be measured simultaneously by a microtiter plate reader within 2 h. Moreover, the quantitative results of HER2 were consistent with those obtained using the enzyme-linked immunosorbent assay kit ( r = 0.9995). Therefore, leveraging the delicate design of Ag + -HCR signal amplification, this enzyme-free, label-free, and effective method has demonstrated to be capable of detecting HER2 in serum due to its high sensitivity. Remarkably, this method may be extended to detect other cancer-related proteins and genes by replacing the corresponding target sequences.

An electrochemical biosensor for HER2 detection in complex biological media based on two antifouling materials of designed recognizing peptide and PEG

Xiqin Yang,Ping Chen,Xi Zhang,Hao Zhou,Zhen Song,Wenlong Yang,Xiliang Luo

A simple tactic for electrochemical determination of a typical biomarker for breast cancer, human epidermal growth factor receptor 2 (HER2), was presented via the construction of a low fouling sensing interface functionalized with polyethylene glycol (PEG) and peptide. The HER2 biosensor was developed based on an electrode modified by the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and Au nanoparticles (AuNPs) as the sensing substrate, and followed by the immobilization of an antifouling PEG and a peptide with both recognizing and antifouling properties. Thanks to the combined antifouling effect of the PEG and peptide, and the specific recognizing ability of the peptide to the target HER2, the developed electrochemical biosensor exhibited strong antifouling performances in complex biofluids, such as human blood and serum, and it was capable of assaying target HER2 within a very wide linear range (1.0 pg mL −1 to 1.0 μg mL −1 ), with an ultralow limit of detection (0.44 pg mL −1 ). The combination of two kinds of antifouling biomaterials (PEG and peptide) offered an effective strategy for the development of low fouling sensing platforms suitable for practical assay in complex biotic environments.

Herceptin-functionalized SK-BR-3 cell membrane-wrapped paclitaxel nanocrystals for enhancing the targeted therapy effect of HER2-positive breast cancer

Qian Wu,Le Tong,Zhiru Zou,Yingqiao Li,Jinyu An,Wenwen Shen,Yu Gao,Ying Liu,Chao Wu

The objective of this study was to prepare Herceptin-functionalized SK-BR-3 cell membrane-wrapped paclitaxel nanocrystals (HCNCs) as a targeted delivery module for HER2-positive breast cancer. According to transmission electron microscopy (TEM) images, HCNCs presented a membrane-coated cubic shape with a particle size of approximately 220 nm. In vitro release test suggested that HCNCs had a certain sustained release effect of paclitaxel (PTX). Cell uptake experiments, in vivo imaging, and tissue distribution experiments demonstrated that HCNCs had excellent targeting ability to homologous tumor cells (SK-BR-3). The results of MTT, flow cytometry, Western blot, cell immunofluorescence staining, and in vivo antitumor experiments proved that HCNCs had a more significant ability to promote HER2-positive breast cancer cell apoptosis and inhibit its proliferation. These results clearly concluded that HCNCs were a promising nano-targeted preparation in anti-HER2-positive breast cancer.

Electrochemiluminescence Aptasensor for HER2-ECD Detection Based on Resonance Energy Transfer between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA Composites

Hui Zhong,Yonghua Yuan,Min Qing,Jianli Zuo,Yueyuan Li,Lijuan Bai

The extracellular domain of the human epidermal growth factor receptor (HER2-ECD) is a breast cancer biomarker. Accurate and sensitive detection of HER2-ECD concentration in serum is crucial in the diagnosis and patient follow-up. Herein, an “off–on” type electrochemiluminescence (ECL) aptasensor based on the resonance energy transfer (RET) between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA was developed for detecting HER2-ECD. First, AuNP-modified g-C3N4 (AuNPs/g-C3N4/PDDA), as a signal substrate, generates ECL signals under the co-reactant peroxodisulfate (S2O82–) in a specific potential range and shows significantly enhanced signal strength and stability. Then, AuPt@ZIF-67 expeditiously quenched the ECL signal of AuNPs/g-C3N4/PDDA because of ECL resonance energy transfer (ECL-RET) between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA. We designed a new aptasensor detection platform for HER2-ECD detection. After specific binding of the aptamer with HER2-ECD, the AuPt@ZIF-67 content in the system decreased, and the ECL response recovered. The biosensor demonstrated a linear range of HER2-ECD detection between 100 fg/mL and 100 ng/mL under ideal circumstances, with a low detection limit of 17.3 fg/mL. Furthermore, this biosensor was successfully tested in human serum samples. This strategy, as a novel ECL system with satisfactory stability and excellent sensitivity, can realize the detection of other biological molecules by changing the probe, which is a promising method.

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

Hollow Mesoporous Selenium Nanoparticles Loaded with Pyrotinib and Coated with Trastuzumab-Functionalized Albumin for Targeted Therapy of HER2-Positive Breast Cancer

Jiaqun Du,Junpeng Sun,Xiaobang Liu,Huan Shi,Chao Wu,Ying Liu,Yang Qiu,Yu Gao

This study aimed to develop trastuzumab (HCT)-functionalized albumin (BSA)-coated, pyrotinib (Ptb)-loaded hollow mesoporous selenium (HSE) nanoparticles (HBHSEP) for the targeted delivery of HER2-positive breast cancer. Characterization of the pharmaceutical properties in vitro revealed that HBHSEP was well dispersed, and the particle size was 172 ± 3.4 nm. In vitro release experiments revealed that HBHSEP effectively controlled the release of Ptb in the tumor microenvironment (high glutathione concentration), with a cumulative release rate of 86.5 ± 4.2% over 48 h. Cell uptake experiments and in vivo imaging confirmed that HBHSEP have good tumor-targeting ability. The results of in vitro cell experiments, such as MTT, flow cytometry, immunofluorescence staining, and in vivo antitumor experiments, confirmed that HBHSEP can significantly promote the apoptosis of SK-BR-3 cells and inhibit their proliferation. These findings strongly show that HBHSEP may be an effective targeted treatment for HER2-positive breast cancer.

Doxorubicin conjugated with a trastuzumab epitope and an MMP-2 sensitive peptide linker for the treatment of HER2-positive breast cancer

Yiwen You,Zhiyuan Xu,Yun Chen

HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH2 (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDYCDGFYACYMDV-NH2, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX via a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as in vitro model systems and nude mice with BT474 xenografts as an in vivo model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower in vitro IC50, and its in vivo extent of inhibition in mice was more evident. During this process, enzymatic cleavage of MAHNP-DOX is critical for its activation and cellular uptake. In addition, a synergistic response was observed after the combination of DOX and AHNP. This effect was probably due to the involvement of AHNP in the PI3K–AKT signaling pathway, which can be largely activated by DOX and leads to anti-apoptotic signals.

Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator

Zhang Yue,Chen Shuyi,Ma Jie,Zhou Xiaobin,Sun Xinchen,Zhou Chenglin

An effective strategy for enzyme-enhanced electrochemical detection of human epidermal growth factor receptor 2 (HER2) is proposed for breast cancer diagnosis. This strategy utilizes a three-dimensional mesoporous covalent organic framework (COF), immobilized horseradish peroxidase (HRP), and a novel redox mediator, 4-acetamidophenol (APAP). The mesoporous structure, with encapsulation effect, and good biocompatibility of COF, makes the functionalized COF an efficient carrier for HRP immobilization (HRP-Ab-AuNPs@COF). It demonstrates superior catalytic activity, stability, and electrochemical performance compared to free HRP, thus making it an ideal probe for simultaneous target recognition and signal amplification. APAP is screened from four candidate phenolic compounds based on its high formal potential (0.32 V vs. Ag/AgCl), rapid electron transfer activity (k app = 2.80 × 10 5 M − 1 s − 1 ), excellent solubility and stability. These properties prove significantly better than the conventional mediator hydroquinone (HQ), achieving a higher signal-to-background ratio. By integrating decorated multi-walled carbon nanotubes as substrate materials, the electrochemical aptasensor achieves a low HER2 detection limit (0.418 pg mL − 1 ) with high specificity. This method’s selectivity surpasses that of the HQ-mediated method by 59–73%. Moreover, the aptasensor can effectively distinguish breast cancer patients and healthy individuals, as well as patients at different stages of the disease with high accuracy (AUC = 0.928). This performance exceeds traditional biomarkers CEA and CA15-3. This work paves novel avenues for innovative applications of COF-immobilized enzymes and the novel mediator APAP in electrochemical biosensing, thus holding significant promise for individualized breast cancer diagnosis and treatment.

Cascaded Aptamers-Governed Multistage Drug-Delivery System Based on Biodegradable Envelope-Type Nanovehicle for Targeted Therapy of HER2-Overexpressing Breast Cancer

Tingxizi Liang,Zhigang Yao,Jie Ding,Qianhao Min,Liping Jiang,Jun-Jie Zhu

Tumor-specific therapeutic platforms with improved targeting efficacy and minimized side effect are crucial in cancer therapy. Capitalizing on the recognition capability and biocompatibility of aptamers, we herein designed a multistage targeted drug-delivery system using multiple biodegradable molecules-enveloped nanovehicle that can be employed to efficiently treat human epithelial growth factor receptor (HER2)-overexpressing breast cancer. In this nanovehicle, two aptamers respectively specific to HER2 and ATP were organized in a hierarchical manner. The outmost HER2 aptamer (HB5) governs the recognition to HER2 protein overexpressed in SK-BR-3 cell lines, while the ATP aptamer incorporated with anticancer drug (−)-epigallocatechin gallate (EGCG) and protamine sulfate in the inner core functions as a switch of drug release in response to abundant intracellular ATP. The targeting and drug locker aptamers were cascaded for active targeting effect and stimuli responsiveness, guaranteeing the site-specific drug transportation and endogenous species-triggered drug release inside the tumor cells. Moreover, nanostructured lipid carriers (NLCs) were constructed to wrap and stabilize the loosely bounded ternary complex, minimizing premature drug leakage potentially encountered by the biomolecule assembled nanocarriers. This multiple biomolecules-enveloped nanovehicle demonstrated improved inhibitory actions on tumor growth and minimum side effect to normal organs and tissues both in vitro and in vivo. The presented nanovehicle built from recognition and therapeutic components in a nontoxic framework offered a promising drug-delivery platform with transport precision and biological safety.

Synthesis and Feasibility Evaluation of a new Trastuzumab Conjugate Integrated with Paclitaxel and 89Zr for Theranostic Application Against HER2-Expressing Breast Cancers

Joo Hee Jang,Sang Jin Han,Jung Young Kim,Kwang Il Kim,Kyo Chul Lee,Chi Soo Kang

Graphical Conjugate for double duty : A new antibody-drug conjugate composed of paclitaxel (PTX), deferoxamine (DFO) and trastuzumab (DFO-trastuzumab-PTX) was prepared using simple conjugation chemistry. The new conjugate displayed instant complexation kinetics with 89 Zr and showed feasible cytotoxic effect and binding property on HER2-positive MDA-MB-231 breast cancer cell showing promising potential as a theranostic agent utilizing chemo-drug and positron emission tomography (PET). The preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)-chelated 89 Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO-trastuzumab-PTX) showed excellent radiolabeling efficiency with 89 Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO-trastuzumab-PTX displayed comparable cytotoxicity with PTX and 89 Zr-DFO-trastuzumab-PTX exhibited HER2 receptor-mediated binding on HER2-positive MDA-MB-231 breast cancer cells. The results of our in vitro study indicate high potential of 89 Zr-DFO-trastuzumab-PTX to be utilized in the theranostic application against HER2-postive breast cancers.