ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Lihong Sun,Jinxia Zhang,Menghong Xu,Lulu Zhang,Qingshuang Tang,Jing Chen,Ming Gong,Suhui Sun,Huiyu Ge,Shumin Wang,Xiaolong Liang,Ligang Cui
Trastuzumab combined with chemotherapy is the first-line treatment for advanced HER2-positive gastric cancer, but it still suffers from limited therapeutic efficiency and serious side effects, which are usually due to the poor delivery efficiency and the drug resistance of tumor cells to the chemotherapeutic drugs. Herein, a type of ultrasound microbubble for simultaneous delivery of sonosensitizers and therapeutic antibodies to achieve targeting combination of sonodynamic therapy and antibody therapy of HER2-positive gastric cancer was constructed from pyropheophorbide-lipid followed by trastuzumab conjugation (TP MBs). In vitro and in vivo studies showed that TP MBs had good biological safety, and their in vivo delivery can be monitored by ultrasound/fluorescence bimodal imaging. With ultrasound (US) located at the tumor area, TP MBs can be converted into nanoparticles (TP NPs) in situ by US-targeted microbubble destruction; plus the enhanced permeability and retention effects and the targeting effects of trastuzumab, the enrichment of sonosensitizers and antibodies in the tumor tissue can be greatly enhanced (∼2.1 times). When combined with ultrasound, TP MBs can not only increase the uptake of sonosensitizers in HER2-positive gastric cancer NCI-N87 cells but also efficiently generate singlet oxygen to greatly increase the killing effect on cells, obviously inhibiting the tumor growth in HER2-positive gastric cancer NCI-N87 cell models with a tumor inhibition rate up to 79.3%. Overall, TP MBs combined with US provided an efficient way for co-delivery of sonosensitizers and antibodies, greatly enhancing the synergistic therapeutic effect on HER2-positive gastric cancer while effectively reducing the side effects.
研究领域:
肿瘤学
·
生物医学工程
·
诊疗学
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DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2022
·
IF 5.76
Ya Zhang,Ning Li,Ying Xu,Xiaofang Liu,Yi Ma,Zhen Huang,Huibo Luo,Changjun Hou,Danqun Huo
Antimonene (AMNFs) is a new kind of sp 2 -bonded honeycomb lattice two-dimensional material with strong rod-rail coupling, stability and hydrophilicity. Compared with graphene, antimonene has better sensitivity in DNA molecular sensing. We developed a suitable biosensor-Cd 2+ [email protected] @ZIF-67 nanocomposite for HER2 biomarker detection. Two-dimensional antimonene can be grown on the surface of ZIF-67 to enhance stability and biocompatibility. The aptamer chain can also be adsorbed on the surface of antimonene, and the complexes of the aptamer and the marker can be detached analytically after targeting the biomarker. The detection limit (LOD) was 4.853 fg/mL within 60 min, the detection range was 0–1000 pg/mL, and the LOD was lower than the existing HER2 aptamer biosensors. The results show that the biosensor has certain applicability and potential, and is expected to be a powerful tool for breast cancer diagnosis in the future.
研究领域:
材料科学
·
纳米技术
·
生物传感
·
癌症诊断
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产品关联
DOI
PubMed
高影响因子
BREAST CANCER RESEARCH
·
2024
·Vol. 26
·期 1
·1-15
·
IF 6.1
Du Jiaqun,Liu Xiaobang,Sun Junpeng,Wu Qian,Hu Yu,Shi Huan,Zheng Li,Liu Ying,Wu Chao,Gao Yu
In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.
研究领域:
药理学
·
肿瘤学
·
纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2020
·
IF 2.22
Qi Dong,Caifeng Wan,Hong Yang,Dongdong Zheng,Li Xu,Zhiguo Zhou,Shaowei Xie,Jing Du,Fenghua Li
A multifunctional targeted nanoplatform combining photothermal therapy and chemotherapy has emerged as a promising strategy for comprehensive therapies of breast cancer. In this study, we constructed human epidermal growth factor receptor 2 (Her2)-targeted gold nanoshelled poly(lactic-co-glycolic acid) hybrid nanocapsules encapsulating perfluorooctyl bromide, superparamagnetic iron oxide nanoparticles, and doxorubicin (Her2-GPDH nanocapsules) as theranostic agent for bimodal ultrasound/magnetic resonance imaging and synergistic photothermal-chemotherapy of Her2-postive breast cancer cells. Her2–GPDH nanocomposites possessed well-defined spherical morphology, and the average diameter was about 296 nm with good dispersion. Targeting assays demonstrated that Her2–GPDH nanocapsules exhibited higher targeting binding to Her2-positive SKBR3 cells than Her2-negative MDA-MB-231cells. The encapsulation efficiency and the loading content of doxorubicin in Her2–GPDH nanocapsules were 39 ± 1.45% and 3.8 ± 0.52%, respectively, and the agent exhibited pH-responsive and near-infrared light-triggered stepwise release behavior of doxorubicin. In vitro, the agent had potential to serve as feasible candidate for ultrasound imaging and T2-weighted magnetic resonance imaging with a relatively high relaxivity. Cell experiments confirmed that the agent had significant photothermal cytotoxicity on SKBR3 cells, and the combined photothermal–chemotherapy could significantly enhance the anti-tumor effect. In summary, the present Her2–GPDH nanocapsules, a novel multifunctional nanoplatform, will offer a new way for early bimodal molecular-level diagnosis and synergistic treatment of Her2-positve breast cancer.
研究领域:
肿瘤学
·
纳米医学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
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.
研究领域:
药学
·
肿瘤学
·
纳米医学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 6
·期 4
·568-579
·
IF 4.543
Zhenhuan Song,Ting Liu,Tianfeng Chen
Efficient therapy of glioblastoma remains a big clinical challenge due to the existence of a blood–brain barrier (BBB) that prevents the delivery of anti-cancer drugs to the brain. In this study, a HER2 antibody-conjugated selenium nanoparticle platform was rationally designed and synthesised and was found to be capable of overcoming the BBB efficiently and delivering anti-cancer cargoes precisely to brain tissues. The BBB-overcoming efficacy of the nanosystem (HER2@NPs) was evaluated using in vitro cell co-culture model and in vivo mouse model. The results demonstrated that HER2 functionalization effectively enhanced BBB permeability of the NPs, which could significantly inhibit the growth of U251 glioblastoma tumor spheroids. Examination of the action mechanisms revealed that HER2@NPs entered the cancer cells through receptor-mediated endocytosis and then triggered DNA damage-mediated p53 signalling pathways. Moreover, by using superparamagnetic iron oxide nanoparticles (SPIONs) as a probe in a clinically used magnetic resonance imaging (MRI) system, we found that HER2@NPs effectively deliver SPIONs into the brain. Taken together, this study provides a cancer-targeting nanosystem for the delivery of anti-cancer drugs and MRI contrast agents overcoming the BBB to enable a precise future theranosis of malignant glioma in humans.
研究领域:
药学
·
神经科学
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癌症研究
·
纳米技术
·
医学影像
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Jingjing Bao,Wenjun Zhang,Weixian Zhou,Mingming Lv,Cheng Lu,Hong Yu
Human epidermal growth factor receptor 2 (HER2)-positive is a particularly aggressive type of the breast cancer. Because of the evidence has revealed that accurate HER2 status detection is crucial for prognosis and treatment strategy selection, great effort has been taken to develop assays for sensitive and accurate quantification of HER2. However, nonspecific amplification effect of most current assays limits the quantification accuracy of low abundance HER2. In the present work, we developed an LC-MS/MS-based quasi-targeted proteomics strategy coupled with hybridization chain reaction (HCR) for amplification of the HER2 protein signal. In the described strategy, the aptamer triggered the HCR system to undergo a cascade of hybridization events, with the two locked hairpins conjugated to the substrate peptide to form aptamer–HCR peptide probes. The membrane protein HER2 was recognized by probe and the signal was to be converted and then amplified into the mass response of the reporter peptide, which could be quantified using LC-MS/MS. The signal intensity was approximately five fold greater than that without signal amplification. Finally, the developed assay was applied for the quantitative analysis of HER2 in breast cell lines and monitor the dynamic change of HER2 in drug induced HER2 negative cells. The result demonstrated that combination of HCR signal amplification and mass spectrometry provides a novel approach for simple, accurate, and quantitative monitoring of low abundance protein.
研究领域:
癌症生物学
·
蛋白质组学
·
分子生物学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Yuliang Sun,Wenlong Zhang,Yilin Lu,Yanan He,Badrul Yahaya,Yanli Liu,Juntang Lin
In tumor treatment, the deposition of nanoenzymes in normal tissues and cause potential side effects are unavoidable. Here, we designed an intelligent biomimetic nanoenzymes carrier platform (MSC intelligent ) that endows the carrier platform with “wisdom” by introducing Affibody-Notch(core)-VP64-GAL4/UAS-HSV-TK artificial signal pathways to mesenchymal stem cells (MSCs). This intelligent nanoenzymes carrier platform is distinguished from the traditional targeting tumor microenvironment or enhancing affinity with tumor, which endue MSC intelligent with tumor signal recognition capacity, so that MSC intelligent can autonomously distinguish tumor from normal tissue cells and feedback edited instructions. In this study, MSC intelligent can convert tumor signals into HSV-TK instructions through artificial signal pathway after recognizing Her2 (+) tumor. Subsequently, the synthesized HSV-TK can rupture MSC intelligent under the mediation of ganciclovir, and release the preloaded Cu/Fe nanocrystal clusters to kill the tumor accurately. Meanwhile, MSC intelligent without recognizing tumors will not initiate the HSV-TK instructions, thus being unresponsive to GCV and blocking the release of nanoenzymes in normal tissues. Consequently, MSC intelligent is the first intelligent biomimetic nanoenzymes carrier platform, which represents a new biomimetic nanoenzymes targeting mode.
研究领域:
癌症生物学
·
纳米技术
·
分子生物学
·
干细胞研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
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.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemistryOpen
·
2019
·Vol. 8
·期 4
·451-456
·
IF 2.205
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.
研究领域:
肿瘤学
·
药理学
·
核医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Medicine
·
2021
·
IF 5.093
Guo Liting,Zhang Hongming,Liu Ping,Mi Tianai,Ha Da,Su Li,Huang Lei,Shi Yan,Zhang Jun
Objective: The purpose of this study was to investigate the anticancer activity and the potential imaging use of the innovative combination of magnetic nanoparticles (MNPs)-Fe3O4, paclitaxel (PTX), and trastuzumab (Herceptin) in HER2-positive breast cancer.Methods: MNPs-Fe3O4 was synthesized and underwent water phase transfer and hydrophobic molecular loading, and its surface was then coupled with Herceptin mono-antibody. The morphological characteristics of MNPs-Fe3O4 were observed under transmission electron microscopy (TEM). Effects of PTX-Herceptin-MNPs-Fe3O4 on breast cancer cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,4-diphenyltetrazolium bromide assay and the flow cytometric apoptosis assay. To establish a xenograft model, we injected breast cancer SK-BR-3 cells into the left thighs of nude mice. We measured the effect of PTX-Herceptin-MNPs-Fe3O4 on tumor growth by measuring tumor size and calculating inhibition rate with immunohistochemistry analysis further performed, and analyzed MNPs-Fe3O4 accumulation in tumor lesions using in vivo magnetic resonance imaging and in vivo fluorescence imaging.Results: Most MNPs were in spherical shape of about 10 nm in diameter observed under TEM. PTX-Herceptin-MNPs-Fe3O4 showed greater cytotoxic effects, and induced a higher apoptosis rate of SK-BR-3 cells than all the other groups, with corresponding changes of apoptosis-related proteins. Meanwhile, the in vivo tumor xenograft model showed that tumor inhibition rate in the PTX-Herceptin-MNPs-Fe3O4 group was higher than in the PTX-Herceptin group. Furthermore, PTX-Herceptin-MNPs-Fe3O4 enhanced the T2 imaging contrast enhancement effect on tumors in tumor-bearing mice.Conclusion: The novel PTX-Herceptin-MNPs-Fe3O4 combination may represent a promising alternative breast cancer treatment strategy and may facilitate tumor imaging.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Qizhi Liang,Qianxi Zhou,Hai Shi,Shuai Wu,Jiahua Yang,Tianyu Zeng,Jing Zhao,Yongmei Yin,Genxi Li
The controllable assembly of metal-organic frameworks (MOFs) nanomaterials is an effective means to enhance their application capabilities. In this paper, a novel method is reported to control MOFs assembly by using a DNA framework material, a tetrahedral DNA nanostructure (TDN) labeled with phosphate groups at the vertex. In particular, various well-defined superstructures can be tailored by regulating the number of phosphate groups that coordinate with catalytic Zr-MOFs to create polymeric MOFs superstructures (Poly(MOFs)), exhibiting excellent catalytic activities and molecular recognition ability as well as greatly amplified signal readout. Furthermore, based on the DNA framework-controlled Poly(MOFs), a colorimetric biosensor with excellent analytical performance is fabricated for improving the diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. It is demonstrated that the quantification of HER2 protein can be achieved at molecular level with the limit of detection (LOD) of 12 pg L -1 and cellular level with the LOD of 10 cells. More importantly, the detection of HER2 in the serum of breast cancer patients have been achieved, thus HER2-positive and triple-negative breast cancer patients can be well distinguished. Considering the substitutability of the target, this study shows great potential in biomedical research as well as clinical applications.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
癌症诊断
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）