Supramolecular Nanofibers Formed by Enzyme-Instructed Self-Assembly for SKBR-3 Cell Selective Inhibition.

Cell-targeted peptides are recommended for precision cancer treatment due to their comparable targeting properties, small molecular size, and good biocompatibility. However, unpredictable bioactivity, low penetration rate and poor stability greatly limit its efficacy. Supramolecular self-assembly based on synthetic peptide has great potential to solve related problems and achieve better therapeutic effects. Herein, we report and compare the effects of two different assembly pathway, heating-cooling, and enzyme instruction, on the penetrability of SKBR-3 cell targeted peptides. It was found that enzyme-instructed self-assembly (EISA) resulted in hydrogels composed of uniform supramolecular nanofibers, whereas heating-cooling resulted in solutions and precipitations composed of slightly different nanoparticles. The nanofibers formed by EISA showed enhanced cellular uptake (2.54 µM), which was significantly higher than the 1.06 µM of the nanoparticles formed by temperature regulation. Thus, EISA is a promising strategy to improve the cell penetration rate of targeted peptides and could provide a better solution for precision cancer treatment.

The Hippo Transducer YAP/TAZ as a Biomarker of Therapeutic Response and Prognosis in Trastuzumab-Based Neoadjuvant Therapy Treated HER2-Positive Breast Cancer Patients.

BACKGROUND: We explored the therapeutic and prognostic effect of YAP/TAZ intensityinHER2-positive breast cancer patients. We also investigated the relationship between YAP/TAZ expression and Trastuzumab-resistance. METHODS: We collected clinicopathological information from 397 cases. We evaluated therapeutic and prognostic effect of YAP/TAZ and other variables. We also cultivated Trastuzumab-resistance cell lines and explored relationship between YAP/TAZ and Trastuzumab-resistance. RESULTS: Over-expression of YAP/TAZ was remarkable in Trastuzumab-resistant cells, and so did HER3 and HER2/HER3 heterodimer. Inhibition of YAP/TAZ expression reversed Trastuzumab-resistance.YAP/TAZ deficiency contributed to favorable therapeutic response, and so did hormone receptor insufficiency and chemotherapy dosage inferiority. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival. Over-expression of YAP/TAZ was obvious in recurrent cases in comparison with their matching primary lesions. Prognostic superiority of insufficient YAP/TAZ intensity was more outstanding in hormone receptor negative cases. Over-expression of YAP/TAZ and HER3 was generally synchronous. Absence of HER3 expression in residual lesions might correlate with better breast cancer-free survival. CONCLUSIONS: Over-expression of YAP/TAZ as well as HER-3 and HER2/HER3 heterodimer was synchronously remarkable in Trastuzumab-resistant cell lines. Inhibition of YAP/TAZ expression reversed Trastuzumab resistance. Deficient YAP/TAZ intensity as well as insufficient hormone receptor intensity and high chemotherapy dosage contributed to favorable therapeutic response. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival, and so did absence of HER3expression in residual lesions. Prognostic superiority of YAP/TAZ expression depended on hormone receptor status. Cases with synchronous over-expression of YAP/TAZ and HER3 suffered poor survival, which revealed the potential effect of YAP/TAZ-HER2/HER3 crosstalk in prognosis of HER2-positive patients.

lncRNA HOTAIR promotes malignant biological behaviors of breast cancer SKBR3 cells through miR-519d-3p/CCND1 axis / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the effect of lncRNA HOTAIR/miR-519d-3p/cyclin D1 (CCND1) axis on the proliferation and metastasis of breast cancer cells and its underlying mechanism. Methods: A total of 50 pairs of breast cancer tissues and corresponding para-cancer tissues resected from breast cancer patients in the Department of Breast Surgery, the Third Hospital of Nanchang from March 2017 to February 2019 were collected for this study. The expression level of HOTAIR in breast cancer tissues and paired paracancer tissues was detected by qPCR, in addition, the expressions of HOTAIR and miR-519d-3p in normal breast epithelial cells and breast cancer cell lines were also detected. Breast cancer SKBR3 cells were divided into NC group (without any treatment), si-HOTAIR group, mir-519d-3p mimics group, miR-519d-3p mimic+pcHOTAIR group, miR-519d-3p mimic+pcCCND1 group, and si-HOTAIR+ pcCCND1 group. The proliferation ability of SKBR3 cells was detected by CCK-8. Invasion and migration of SKBR3 cells were detected by Transwell. The expression levels of E-cadherin, N-cadherin, Vimentin and CCND1 in SKBR3 cells were detected by Western blotting. The targeting relationship between HOTAIR and miR-519d-3p, miR-519d-3p and CCND1 was detected by Dualluciferase reporter gene system. Results: HOTAIR was highly expressed in breast cancer tissues and cell lines, with the highest expression in SKBR3 cells. HOTAIR knockdown significantly inhibited the proliferation, invasion and migration of SKBR3 cells, as well as increased the expression level of E-cadherin and decreased the expression levels of N-cadherin and Vimentin. Dual-luciferase reporter gene assay showed that HOTAIR targetedly down-regulated the expression of miR-519d-3p, and miR-519d-3p targetedly downregulated the expression of CCND1. Further studies showed that knockout of HOTAIR inhibited the EMT, proliferation, invasion and migration of SKBR3 cells through enhancing the inhibitory effect of miR-519d-3p on CCND1 expression (all P<0.05). Conclusion: HOTAIR knockdown inhibits proliferation and metastasis of SKBR3 cells by regulating the axis of miR-519d-3p/CCND1.

Conjugated Polymer-Based Photoelectrochemical Cytosensor with Turn-On Enable Signal for Sensitive Cell Detection.

In this work, a new photoelectrochemical (PEC) cytosensor was constructed by using cationic polyfluorene derivative, poly(9,9-bis(6'-(N,N,N,-trimethylammonium)hexyl)fluorene-co-alt-1,4-phenylene)bromide (PFP) as the photoelectric-responsive material for sensitive cell detection. Positive-charged PFP with high photoelectric conversion efficiency can generate robust photocurrent under light illumination. In the PEC cytosensor, 3-phosphonopropionic acid was linked to the indium tin oxide electrode, followed by modification with antiepithelial-cell-adhesion-molecule (EpCAM) antibody via amide condensation reaction. Thus, target SKBR-3 cells with overexpressed EpCAM antigen could be captured onto the electrode via the specific antibody-antigen interactions. Upon adding cationic PFP, a favorable electrostatic interaction between cationic PFP and negatively charged cell membrane led to a turn-on detection signal for target SKBR-3 cells. This new cytosensor not only exhibits good sensitivity because of the good photoelectric performance of conjugated polymers, but also offers decent selectivity to target cells by taking advantage of the specific antibody-antigen recognition.

Amphiphilic gemini pyridinium-mediated incorporation of Zn(II)meso-tetrakis(4-carboxyphenyl)porphyrin into water-soluble gold nanoparticles for photodynamic therapy.

Zn-containing porphyrins are intensely investigated for their ability to form reactive oxygen species and thereby being potent photosensitizers for use in photodynamic therapy (PDT). Some of the drawbacks of the PDT approach, such as unspecific distribution, could be addressed by means of photosensitizer drug delivery systems. In this work, we synthesize and characterize new water-soluble gold nanoparticles (GNP) stabilized by a mixture of a polyethyleneglycol-containing thiol (to improve water solubility) and a new amphiphilic gemini-type pyridinium salt, which also acts as promotor of the incorporation of the anionic photosensitizer Na-ZnTCPP into the GNP. The obtained GNP have sizes between 7 and 10nm, as observed by Transmission Electron Microscopy. The incorporation of the photosensitizer caused an increase in the hydrodynamic size, detected by Dynamic Light Scattering, as well as a shift in the Surface Plasmon Resonance peak on the GNP UV-vis absorption spectra. The presence of the photosensitizer in the GNP was corroborated using Fluorescence Spectroscopy. The amount of Na-ZnTCPP was found to be 327 molecules per GNP. The porphyrin-containing Na-ZnTCPP-1·GNP showed good enhanced ability to produce singlet oxygen, compared to free Na-ZnTCPP. Their cytotoxicity and phototoxicity were investigated in vitro using two different human breast cell lines, one of tumoral origin (SKBR-3) and another of normal epithelium origin (MCF-10A). SKBR-3 cells showed higher sensitivity to Na-ZnTCCP and Na-ZnTCPP-1·GNP in dark conditions. After irradiation, no significant differences were observed between both cell lines except for 1µM Na-ZnTCCP-1·GNP where SKBR-3 cells were also more sensitive.