An Implantable Magnetic Vascular Scaffold for Circulating Tumor Cell Removal In Vivo.

An integrated trapped device (ITD) capable of removal of circulating tumor cells (CTCs) can assuage or even prevent metastasis. However, adhesion repertoires are ordinarily neglected in the design of ITDs, possibly leading to the omission of highly metastatic CTC and treatment failure. Here a vascular-like ITD with adhesive sites and wireless magnetothermal response to remove highly metastatic CTC in vivo is presented. Such a vascular-like ITD comprises circumferential well-aligned fibers and artificial adhesion repertoires and is optimized for magnetothermal integration. Continuous and repeated capture in a dynamic environment increases capture efficiency over time. Meanwhile, the heat generation of the ITD leads to the capture of CTC death owing to cell heat sensitivity. Furthermore, the constructed bioinspired ultrastructure of the ITD prevents vascular blockage and induces potential vascular regeneration. Overall, this work defines an extendable strategy for constructing adhesion repertoires against intravascular shear forces, provides a vascular-like ITD for reducing CTC counts, and is expected to alleviate the risk of cancer recurrence.

Stabilizing Enzymes in Plasmonic Silk Film for Synergistic Therapy of In Situ SERS Identified Bacteria.

Increasing antibiotic resistance becomes a serious threat to public health. Photothermal therapy (PTT) and antibacterial enzyme-based therapy are promising nonresistant strategies for efficiently killing drug-resistant bacteria. However, the poor thermostability of enzymes in PTT hinders their synergistic therapy. Herein, antibacterial glucose oxidase (GOx) is embedded in a Ag graphitic nanocapsule (Ag@G) arrayed silk film to fabricate a GOx-synergistic PTT system (named silk-GOx-Ag@G, SGA). The SGA system can stabilize GOx by a vitrification process through the restriction of hydrogen bond and rigid ß-sheet, and keep the antibacterial activity in the hyperthermal PTT environment. Moreover, the arrayed Ag@G possesses excellent chemical stability due to the protection of graphitic shell, providing stable plasmonic effect for integrating PTT and surface enhanced Raman scattering (SERS) analysis even in the GOx-produced H2 O2 environment. With in situ SERS identification of bacterial intrinsic signals in the mouse wound model, such SGA realizes superior synergistic antibacterial effect on the infected Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus in vivo, while without causing significant biotoxicity. This system provides a therapeutic method with low resistance and in situ diagnosis capability for efficiently eliminating bacteria.

Interaction-Transferable Graphene-Isolated Superstable AuCo Nanocrystal-Enabled Direct Cyanide Capture.

Noble metals with strong plasmons have been widely used as enhancement substrates for molecule identification. However, cyanide, a toxic and important signaling molecule with a corrosive nature to noble metals, makes direct recognition challenging. Herein a novel superstable magnetic graphene-isolated AuCo nanocrystal (MACG) has been designed. Such graphene isolation enables superior stability without corrosion. Moreover, unexpectedly, although graphene isolated direct contact between Au and cyanide, their interaction was transferable and remained, which gifted MACGs direct cyanide capture capability with no specific ligands needed. Density functional theory calculations and natural bond orbital analysis indicated that the graphene isolation only slightly affected the charge transfer and that a relatively strong interaction was maintained between Au and cyanide. MACGs were utilized for efficient cyanide capture and clearance in various hydrologic environments and sensitive in vivo cyanide capture in C. elegans infected with P. aeruginosa, a pathogen with cyanide as the biomarker, indicating promise for various applications.

Surfactant-Free Interface Suspended Gold Graphitic Surface-Enhanced Raman Spectroscopy Substrate for Simultaneous Multiphase Analysis.

Simultaneous multiphase detection of multiplex analytes is important, albeit challenging, especially in pharmaceuticals analysis since drugs with lipid and water solubility were often administrated together for synergistic therapy. Surface-enhanced Raman spectroscopy (SERS) is a label-free and sensitive tool for multiplex analytes detection at multiphase interfaces. However, the requirements of inducers or surfactant surface modification of the SERS substrate have restricted extensive applications. Herein, we developed a graphene-isolated-Au-nanocrystal based multiphase analysis system. Unexpectedly, the gold graphitic SERS substrate can simply suspend at the interface of the different phase without the involvement of any surfactant. Therefore, the proximity of substrate with analyte molecules remains unaffected. Such suspended substrate not only ensures sensitive SERS detection but also enables the enrichment of analytes from the different phase simultaneously without interference. Moreover, the graphitic shell of the SERS substrate has a unique vibration band located in the Raman biological silence region which is utilized as the internal standard and improves the SERS quantification accuracy. Efficient ex vivo multiphase enrichment and detection of mimic lipid- and water-soluble drugs injected into mice were demonstrated with such gold graphitic substrate, showing the potential of this simultaneous multiplex pharmacokinetic analysis.

Isotopic graphene-isolated-Au-nanocrystals with cellular Raman-silent signals for cancer cell pattern recognition.

For cancer diagnosis, technologies must be capable of molecular recognition, and they must possess a built-in pattern recognition component for efficient imaging and discrimination of targeted cancer cells. Surface enhanced Raman scattering (SERS) tags based on plasmonically active nanoparticles hold promise for accurate and efficient cancer cell recognition, owing to ultra-narrow peak and sensitive optical properties. However, a complex fingerprint spectrum increases data analysis difficulty, making it necessary to develop multicolor SERS tags with a simple fingerprint spectrum. To address this, we herein fabricated SERS-encoded nanoparticles (NPs) with stable and simple fingerprint spectrum through synthesis of isotopic cellular Raman-silent graphene-isolated-Au-nanocrystals (GIANs) and conjugation with phospholipid-polyethylene glycol-linked aptamers to target proteins overexpressed on the cancer cell surface. GIANs, which possess the properties of graphitic nanomaterials, such as super-stable optical properties and high Raman cross-section, showed enhanced SERS signals. The 2D-band Raman shift of GIAN, which located in the cellular Raman-silent region, was easily regulated through fabrication of isotopic GIANs without changing their molecular structure. Such GIAN tags demonstrated multiplexed Raman imaging capability, both in vivo and in vitro, with low background interference. Moreover, cell membrane protein (nucleolin, mucin and epithelial cell adhesion molecule)-specific, aptamer-conjugated isotopic GIANs were fabricated and feasibly applied to built-in coding for rapid imaging and pattern recognition of targeted cancer cells. Such isotopic GIAN-aptamer-encoders show high potential for efficient cancer cell identification and diagnosis.

Elucidating the cellular uptake mechanism of aptamer-functionalized graphene-isolated-Au-nanocrystals with dual-modal imaging.

Elucidating the endocytosis and metabolism of nanoparticles in cells could improve the diagnostic sensitivity and therapeutic efficiency. In this work, we explore the cellular uptake mechanism of a biocompatible nanocrystal nanostructure, graphene-isolated-Au-nanocrystals (GIANs), by monitoring the intrinsic Raman and two-photon luminescence signals of GIANs in live cells. Aptamers functionalized on the GIAN nanostructure through simple, but strong, π-π interactions entered the cells through a clathrin-dependent pathway, while unmodified GIANs mainly entered the cells through a caveolae-mediated endocytosis pathway. Thus, it can be concluded that the mechanism of cellular uptake in these graphene-isolated-Au-nanocrystal nanostructures is determined by the presence or absence of aptamer modification.