Wenjuan Ma

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.

Self-Assembled Tetrahedral DNA Nanostructures Promote Neural Stem Cell Proliferation and Neuronal Differentiation

Stem cell-based therapy is considered a promising approach for the repair of nervous tissues. Neural stem cells (NSCs) cannot proliferate or differentiate efficiently; hence, different biomaterials have been explored to improve NSC proliferation and differentiation. However, these agents either had low bioavailability or poor biocompatibility. In this work, our group investigated the effects of tetrahedral DNA nanostructures (TDNs), a novel DNA biological material, on the self-renew and differentiation of neuroectodermal (NE-4C) stem cells. We observed that TDN treatment promoted self-renew of the stem cells via activating the Wnt/β -catenin pathway. In addition, our findings suggested that NE-4C stem cells neuronal differentiation could be promoted effectively by TDNs via inhibiting the notch signaling pathway. In summary, this is the first report about the effects of TDNs on the proliferation and differentiation of NE-4C stem cells and the results demonstrate that TDNs have a great potential in nerve tissue regeneration.

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.

Electrospun Poly (3-Hydroxybutyrate-Co-4-Hydroxybutyrate)/Graphene Oxide Scaffold: Enhanced Properties and Promoted in Vivo Bone Repair in Rats

Bone tissue engineering emerges as an advantageous technique to achieve tissue regeneration. Its scaffolds must present excellent biomechanical properties, where bare polymers poorly perform. Development of new biomaterials with high osteogenic capacity is urgently pursued. In this study, an electrospun poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/graphene oxide (P34HB/GO) nanofibrous scaffold is successfully fabricated and characterized. The effects of GO amount on scaffold morphology, biomechanical properties, and cellular behaviors are investigated. GO reduces the fiber diameter and enhances porosity, hydrophilicity, mechanical properties, cellular performance, and osteogenic differentiation of scaffolds. P34HB/GO triumphs over P34HB in in vivo bone regeneration in critical-sized calvarial defect of rats. We believe that this study is the first to evaluate the capability of in vivo bone repair of electrospun P34HB/GO scaffold. With facile fabrication process, favorable porous structures, enhanced biomechanical properties, and fast osteogenic capability, P34HB/GO scaffold holds practical potentials for bone tissue engineering application.

Effect of Tetrahedral DNA Nanostructures on Proliferation and Osteo/Odontogenic Differentiation of Dental Pulp Stem Cells via Activation of the Notch Signaling Pathway

Dental pulp stem cells (DPSCs) derived from the human dental pulp tissue have multiple differentiation capabilities, such as osteo/odontogenic differentiation. Therefore, DPSCs are deemed as ideal stem cell sources for tissue regeneration. As new nanomaterials based on DNA, tetrahedral DNA nanostructures (TDNs) have tremendous potential for biomedical applications. Here, the authors aimed to explore the part played by TDNs in proliferation and osteo/odontogenic differentiation of DPSCs, and attempted to investigate if these cellular responses could be driven by activating the canonical Notch signaling pathway. Upon exposure to TDNs, proliferation and osteo/odontogenic differentiation of DPSCs were dramatically enhanced, accompanied by up regulation of Notch signaling. In general, our study suggested that TDNs can significantly promote proliferation and osteo/odontogenic differentiation of DPSCs, and this remarkable discovery can be applied in tissue engineering and regenerative medicine to develop a significant and novel method for bone and dental tissue regeneration.

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.

Inhibiting Methicillin-Resistant Staphylococcus aureus by Tetrahedral DNA Nanostructure-Enabled Antisense Peptide Nucleic Acid Delivery

One of the biggest obstacles for the use of antisense oligonucleotides as antibacterial therapeutics is their limited uptake by bacterial cells without a suitable carrier, especially in multi-drug-resistant bacteria with a drug efflux mechanism. Existing vectors, such as cell-penetrating peptides, are inefficient and nontargeting, and accordingly are not ideal carriers. A noncytotoxic tetrahedral DNA nanostructure (TDN) with a controllable conformation has been developed as a delivery vehicle for antisense oligonucleotides. In this study, antisense peptide nucleic acids (asPNAs) targeting a specific gene ( ftsZ) were efficiently transported into methicillin-resistant Staphylococcus aureus cells by TDNs, and the expression of ftsZ was successfully inhibited in an asPNA-concentration-dependent manner. The delivery system specifically targeted the intended gene. This novel delivery system provides a better platform for future applications of antisense antibacterial therapeutics and provides a basis for the development of a new type of antibacterial drug for multi-drug-resistant bacterial infections.

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).

Neuroprotective Effect of Tetrahedral DNA Nanostructures in a Cell Model of Alzheimer’s Disease

Accumulating evidence supports the abnormal deposition of amyloid β-peptide (Aβ) as the main cause of Alzheimers disease (AD). Therefore, fighting against the formation, deposition, and toxicity of Aβ is a basic strategy for the treatment of AD. In the process of in vitro nerve cell culture, screening out drugs that can antagonize a series of toxic reactions caused by β-amyloid deposition has become an effective method for the follow-up treatment of AD. Our previous studies showed that tetrahedral DNA nanostructures (TDNs) had good biocompatibility and had some positive effects on the biological behavior of cells. In this study, the main aim of our work was to explore the effects and potential mechanism of TDNs in protecting neuronal PC12 cells from the toxicity of Aβ. Our study demonstrated that TDNs can protect and rescue PC12 cell death through Aβ25-35-induced PC12 cell apoptosis. Further studies showed that TDNs significantly improved the apoptosis by affecting the abnormal cell cycle, restoring abnormal nuclear morphology and caspase activity. Western blot analysis showed that TDNs could prevent the damage caused by Aβ deposition by activating the ERK1/2 pathway and thus be a potential therapeutic agent with a neuroprotective effect in Alzheimers disease. Our finding provides a potential application of TDNs in the prevention and treatment of AD.