Huanhuan Zhang,Xuan Cai,Hongli Zhao,Wenqian Sun,Zhenxing Wang,Minbo Lan
Developing nanomaterials as alternatives of enzymes is of great significance to realize qualification and quantitation of superoxide anion (O 2 − ), which has been proved to play a crucial role in physiological condition. In this work, a novel electrochemical catalyst of cobalt nanoparticle doped porous cubic carbon (Co-PCC) was prepared through the calcination of zeolitic imidazolate framework-67 (ZIF-67), which was obtained from one-step synthesis. Then Co-PCC was used to construct enzyme-free electrochemical sensor for the detection of O 2 − . The response of H 2 O 2 , though much lower than that of O 2 − , was also caught by the Co-PCC/SPCE. The fabricated sensor exhibited obvious response towards O 2 − in the range of 0.8–76.8 μM (R 2 = 0.997) with a high sensitivity of 3.59 × 10 −4 mA μM −1 cm −2 and a limit of detection of 0.41 μM (S/N = 3). In addition, the proposed sensor can be used to detect O 2 − released from SK-BR-3 cells, which makes it possible to monitor the dynamic change of O 2 − in living cells.
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.
Accurate and ultrasensitive evaluation of human epidermal growth factor receptor 2 (HER2) protein is key to early diagnosis and subtype differentiation of breast cancer. Single-cell analyses to reduce ineffective targeted therapies due to breast cancer heterogeneity and improve patient survival remain challenging. Herein, we reported a novel droplet microfluidic combined with an instant cation exchange signal amplification strategy for quantitative analysis of HER2 protein expression on single cells. In the 160 μm droplets produced by a tapered capillary bundle, abundant Immuno-CdS labeled on HER2-positive cells were replaced by Ag + to obtain Cd 2+ that stimulated Rhod-5N fluorescence. This uniformly distributed and instantaneous fluorescence amplification strategy in droplets improves sensitivity and reduces signal fluctuation. Using HER2 modified PS microsphere to simulate single cells, we obtained a linear fitting of HER2-modified concentration and fluorescence intensity in microdroplets with the limit detection of 11.372 pg mL −1 . Moreover, the relative standard deviation (RSD) was 4.2-fold lower than the traditional immunofluorescence technique (2.89% vs 12.21%). The HER2 protein on SK-BR-3 cells encapsulated in droplets was subsequently quantified, ranging from 9862.954 pg mL −1 and 205.26 pg mL −1 , equivalent to 9.795 × 10 6 and 2.038 × 10 5 protein molecules . This detection system provides a universal platform for single-cell sensitive quantitative analysis and contributes to the evaluation of HER2-positive tumors.
In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.
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