Dually stimulative single-chain polymeric nano lock with dynamic ligands for sensitive detection of circulating tumor cells.

Circulating tumor cells (CTCs) are important markers for cancer diagnosis and monitoring. However, CTCs detection remains challenging due to their scarcity, where most of the detection methods are compromised by the loss of CTCs in pre-enrichment, and by the lack of universal antibodies for capturing different kinds of cancer cells. Herein, we report a single-chain based nano lock (SCNL) polymer incorporating dually stimulative dynamic ligands that can bind with a broad spectrum of cancer cells and CTCs overexpressing sialic acid (SA) with high sensitivity and selectivity. The high sensitivity is realized by the polymeric single chain structure and the multi-valent functional moieties, which improve the accessibility and binding stability between the target cells and the SCNL. The highly selective targeting of cancer cells is achieved by the dynamic and dually stimulative nano lock structures, which can be unlocked and functionalized upon simultaneous exposure to overexpressed SA and acidic microenvironment. We applied the SCNL to detecting cancer cells and CTCs in clinical samples, where the detection threshold of SCNL reached 4 cells/mL. Besides CTCs enumeration, the SCNL approach could also be extended to metastasis assessment through monitoring the expressing level of surface SA on cancer cells.

Muscle-inspired double-network hydrogels with robust mechanical property, biocompatibility and ionic conductivity.

Inspired by muscle architectures, double network hydrogels with hierarchically aligned structures were fabricated, where cross-linked cellulose nanofiber (CNF)/chitosan hydrogel threads obtained by interfacial polyelectrolyte complexation spinning were collected in alignment as the first network, while isotropic poly(acrylamide-co-acrylic acid) (PAM-AA) served as the second network. After further cross-linking using Fe3+, the hydrogel showed an outstanding mechanical performance, owing to effective energy dissipation of the oriented asymmetric double networks. The average strength and elongation-at-break of PAM-AA/CNF/Fe3+ hydrogel were 11 MPa and 480 % respectively, which the strength was comparative to that of biological tissues. The aligned CNFs in the hydrogels provided probable ion transport channels, contributing to the high ionic conductivity, which was up to 0.022 S/cm when the content of LiCl was 1.5 %. Together with superior biocompatibility, the well-ordered hydrogel showed a promising potential in biological applications, such as artificial soft tissue materials and muscle-like sensors for human motion monitoring.

An Innovative Solvent-Responsive Coiling-Expanding Stent.

Coronary artery disease is the "first killer" in the world, while the classical treatment for this disease is to implant stent. An ideal vascular stent should be nontoxic with self-expanding characteristics, quick expanding speed, and appropriate mechanical supporting property. However, no existing vascular stent covers all properties. Herein, a two-way shape-memory cellulose vascular stent, which can realize shape adjustments by mild solutions such as water and alcohol, is constructed. The shape-memory characteristics, mechanical properties, cell toxicity, and biocompatibility, are systemically investigated by ex vivo experiment as well as molecule simulation and theoretical modeling, revealing that the achieved bilayer two-way shape-memory films (BSMFs) can be used as an artificial vascular stent. In particular, this vascular stent made from BSMFs shows superb biocompatibility according to live/dead cell viability assays. Ex vivo experiments reveal that the novel vascular stent can support arteria coronaria sinistra, or the left main coronary artery, at the opening state while the cross-section of the vessel becomes two times larger than that of the initial state after implantation. Thus, it is believed that effective and scalable BSMFs can make meritorious fundamental contributions to biomaterials science and practical applications such as vascular stents.

Dual Enzyme-Like Performances of PLGA Grafted Maghemite Nanocrystals and Their Synergistic Chemo/Chemodynamic Treatment for Human Lung Adenocarcinoma A549 Cells.

In recent years, the emergence of non-toxic but catalytically active inorganic nanoparticles has attracted great attention for cancer treatment, but the therapeutic effect has been affected by the limited reactive oxygen species in tumors. Therefore, the combination of chemotherapy and chemodynamic therapy is regarded as a promising therapeutic strategy. In this paper, we reported the preparation and bioactivity evaluation of poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe2O3 nanoparticles with dual response of endogenous peroxidase and catalase like activities. Our hypothesis is that PLGAgrafted γ-Fe2O3 nanoparticles could be used as a drug delivery system for the anti-tumor drug doxorubicin to inhibit the growth of lung adenocarcinoma A549 cells; meanwhile, based on its mimic enzyme properties, this kind of nanoparticles could be combined with doxorubicin in the treatment of A549 cells. Our experimental results showed that the PLGAgrafted γ-Fe2O3 nanoparticles could simulate the activity of catalase and decompose hydrogen peroxide into H2O and oxygen in neutral tumor microenvironment, thus reducing the oxidative damage caused by hydrogenperoxide to lung adenocarcinoma A549 cells. In acidic microenvironment, PLGA grafted γ-Fe2O3 nanoparticles could simulate the activity of peroxidase and effectively catalyze the decomposition of hydrogen peroxide to generate highly toxic hydroxyl radicals, which could cause the death of A549 cells. Furthermore, the synergistic effect of peroxidase-like activity of PLGA-grafted γ-Fe2O3 nanoparticles and doxorubicin could accelerate the apoptosisand destruction of A549 cells, thus enhancing the antitumor effect of doxorubicin-loaded PLGA-grafted γ-Fe2O3 nanoparticles. Therefore, this study provides an effective nanoplatform based on dual inorganic biomimetic nanozymes for the treatment of lung cancer.

Biomimetic Presentation of Cryptic Ligands via Single-Chain Nanogels for Synergistic Regulation of Stem Cells.

Dynamic controlling the nanoscale presentation of synergistic ligands to stem cells by biomimetic single-chain materials can provide critical insights to understand the molecular crosstalk underlying cells and their extracellular matrix. Here, a stimuli-responsive single-chain macromolecular nanoregulator with conformational dynamics is fabricated based on an advanced scale-up single polymeric chain nanogel (SCNG). Such a carefully designed SCNG is capable of mediating a triggered copresentation of the master and cryptic ligands in a single molecule to elicit the synergistic crosstalk between different intracellular signaling pathways, thereby considerably boosting the bioactivity of the presented ligands. This controllable nanoswitching-on of cell-adhesive ligands' presentation allows the regulation of cell adhesion and fate from molecular scale. The modular nature of this synthetic macromolecular nanoregulator makes it a versatile nanomaterial platform to assist basic and fundamental studies in a wide array of research topics.

Rapid and room temperature detection of single nucleotide variation with enhanced discrimination by crowding assisted allele specific extension.

In this paper we report the kinetics based detection of single nucleotide variation (SNV) at room temperature by allele specific extension with different concentrations and types of crowding agents. In general, the crowding conditions enhanced the specificity in the detection of SNV.

Conformational manipulation of scale-up prepared single-chain polymeric nanogels for multiscale regulation of cells.

Folded single chain polymeric nano-objects are the molecular level soft material with ultra-small size. Here, we report an easy and scalable method for preparing single-chain nanogels (SCNGs) with improved efficiency. We further investigate the impact of the dynamic molecular conformational change of SCNGs on cellular interactions from molecular to bulk scale. First, the supramolecular unfoldable SCNGs efficiently deliver siRNAs into stem cells as a molecular drug carrier in a conformation-dependent manner. Furthermore, the conformation changes of SCNGs enable dynamic and precise manipulation of ligand tether structure on 2D biomaterial interfaces to regulate the ligand-receptor ligation and mechanosensing of cells. Lastly, the dynamic SCNGs as the building blocks provide effective energy dissipation to bulk biomaterials such as hydrogels, thereby protecting the encapsulated stem cells from deleterious mechanical shocks in 3D matrix. Such a bottom-up molecular tailoring strategy will inspire further applications of single-chain nano-objects in the biomedical area.