Mengting Liu

Aptamer-modified tetrahedral DNA nanostructure for tumor-targeted drug delivery

Tetrahedral DNA nanostructures (TDNs) are considered promising drug delivery carriers because they are able to permeate cellular membrane and are biocompatible and biodegradable. Furthermore, they can be modified by functional groups. To improve the drug-delivering ability of TDNs, we chose anticancer aptamer AS1411 to modify TDNs for tumor-targeted drug delivery. AS1411 can specifically bind to nucleolin, which is overexpressed on the cell membrane of tumor cells. Furthermore, AS1411 can inhibit NF-κB signaling and reduce the expression of bcl-2. In this study, we compared the intracellular localization of AS1411-modified TDNs (Apt-TDNs) with that of TDNs in different cells under hypoxic condition. Furthermore, we compared the effects of Apt-TDNs and TDNs on cell growth and cell cycle under hypoxic condition. A substantial amount of Apt-TDNs entered and accumulated in the nucleus of MCF-7 cells; however, the amount of Apt-TDNs that entered L929 cells was comparatively less. TDNs entered in much lower quantity in MCF-7 cells than Apt-TDNs. Moreover, there was little difference in the amount of TDNs that entered L929 cells and MCF-7 cells. Apt-TDNs can inhibit MCF-7 cell growth and promote L929 cell growth, while TDNs can promote both MCF-7 and L929 cell growth. Thus, the results indicate that Apt-TDNs are more effective tumor-targeted drug delivery vehicles than TDNs, with the ability to specifically inhibit tumor cell growth.

Notch Signaling Pathway Regulates Angiogenesis via Endothelial Cell in 3D Co‐Culture Model

This study aimed to investigate the role of Notch signaling pathway for angiogenesis in a three‐dimensional (3D) collagen gel model with co‐culture of adipose‐derived stromal cells (ASCs) and endothelial cells (ECs). A 3D collagen gel model was established in vitro by implanting both ASCs from green fluorescent protein‐labeled mouse and ECs from red fluorescent protein‐labeled mouse, and the phenomena of angiogenesis with Notch signaling inducer Jagged1, inhibitor DAPT and PBS, respectively were observed by confocal laser scanning microscopy. Semi‐quantitative PCR and immunofluorescent staining were conducted to detect expressions of angiogenesis‐related genes and proteins. Angiogenesis in the co‐culture gels was promoted by Jagged1 treatment while attenuated by DAPT treatment, compared to control group. In co‐culture system of ASCs and ECs, the gene expressions of VEGFA, VEGFB, Notch1, Notch2, Hes1, Hey1, VEGFR1,and the protein expression of VEGFA, VEGFB, Notch1, Hes1, Hey1 were increased by Jagged1 treatment and decreased by DAPT treatment in ECs. And the result of VEGFR3 was the opposite. However, the same results did not appear completely in ASCs. These results revealed the VEGFA/B‐Notch1/2‐Hes1/Hey1‐ VEGFR1/3 signal axis played an important role in angiogenesis when ASCs and ECs were co‐cultured in a 3D collagen gel model. J. Cell. Physiol. 232: 1548–1558, 2017.

Substrate stiffness regulated migration and angiogenesis potential of A549 cells and HUVECs

Tumor tissue tends to stiffen during solid tumor progression. Substrate stiffness is known to alter cell behaviors, such as proliferation and migration, during which angiogenesis is requisite. Mono‐ and co‐culture systems of lung cancer cell line A549 and human umbilical vein endothelial cells (HUVECs), on polydimethylsiloxane substrates (PDMS) with varying stiffness, were used for investigating the effects of substrate stiffness on the migration and angiogenesis of lung cancer. The expressions of matrix metalloproteinases (MMPs) and angiogenesis‐related growth factors were up‐regulated with the increase of substrate stiffness, whereas that of tissue inhibitor of matrix metalloproteinase (TIMPs) were down‐regulated with increasing substrate stiffness. Our data not only suggested that stiff substrate may promote the migration and angiogenesis capacities of lung cancer, but also suggested that therapeutically targeting lung tumor stiffness or response of ECs to lung tumor stiffness may help reduce migration and angiogenesis of lung tumor.

Tea Polyphenol-Reduced Graphene Oxide Deposition on Titanium Surface Enhances Osteoblast Bioactivity

Graphene, a novel carbon-based material, has been widely used as osteogenic agent for the potential effect on the promotion of osteoblast proliferation. Tea polyphenol-reduced graphene oxide (TPG) is a simple and environmental-friendly raw material to obtain graphene. In this study, TPG was deposited on the Ti substrate to promote the bone regeneration. We prepared a honeycomb-like structure by acid and alkali pretreatment and immobilized the TPG layer (Ti-TPG) on the surface via electrochemical deposition. Scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD) were used to identify the immobilization of TPG on the titanium (Ti) successfully. Furthermore, the biological response of the Ti-TPG surface to rat osteoblast was evaluated. We also studied the cell adhesion, proliferation and expression of ossification genes on the sample. The results revealed that Ti-TPG had an advantage over Ti alloys in modulating cellular activity and Ti-TPG may be a promising coating for biological materials.

Tetrahedral DNA nanostructures facilitate neural stem cell migration via activating RHOA/ROCK2 signalling pathway

The main purpose of current study was to explore the effects of tetrahedral DNA nanostructures (TDNs) on neuroectodermal (NE‐4C) stem cells migration and unveil the potential mechanisms.

Substrate stiffness regulated migration and invasion ability of adenoid cystic carcinoma cells via RhoA/ROCK pathway

Human salivary adenoid cystic carcinoma (SACC) is one of the most common malignant tumours of the salivary gland and has strong migratory and invasive ability, which often lead to poor prognosis and lower survival rate. Tumour tissue tends to stiffen during solid tumour progression. This study aimed to investigate the influence of various substrate stiffness on the migration and invasion of SACC.

Aptamer-targeted DNA nanostructures with doxorubicin to treat protein tyrosine kinase 7-positive tumours

Aptamer sgc8c is a short DNA sequence that can target protein tyrosine kinase 7 (PTK7), which was overexpressed on many tumour cells. This study aimed to fabricate a novelty DNA nanostructure drug delivery system target on PTK7‐positive cells—CCRF‐CEM (human T‐cell ALL).

Tetrahedral DNA nanostructure promote endothelia cells proliferation, migration and angiogenesis via Notch signaling pathway

The problem of tissue vascularization is one of the obstacles that currently restricts the application of tissue engineering products to the clinic. Achieving tissue vascularization and providing adequate nutrients for tissues are an urgent problem to build complex and effective tissue-engineered tissues and organs. Therefore, the aim of this study was to investigate the effect of tetrahedral DNA nanostructures (TDNs), a novel and biocompatible nanomaterial, on angiogenesis. The results showed that TDNs can enter into endothelial cells (ECs) and promote EC proliferation, migration, tube formation, and expressions of angiogenic growth factors at the concentration of 250 nmol L-1, which was accompanied by activation of the Notch signaling pathway. These results provided a theoretical basis for the further understanding and potential use of TDNs in tissue engineering vascularization.