Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions.

Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανß3-integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.

Integrating a Biomineralized Nanocluster for H2S-Sensitized ROS Bomb against Breast Cancer.

Nanomaterial-assisted chemodynamic therapy (CDT) has received considerable attention in recent years. It outperforms other modalities by its distinctive reactive oxygen species (ROS) generation through a nonexogenous stimulant. However, CDT is limited by the insufficient content of endogenous hydrogen peroxide (H2O2). Herein, a biodegradable MnS@HA-DOX nanocluster (MnS@HA-DOX NC) was constructed by in situ biomineralization from hyaluronic acid, to enlarge the ROS cascade and boost Mn2+-based CDT. The acid-responsive NCs could quickly degrade after internalization into endo/lysosomes, releasing Mn2+, H2S gas, and anticancer drug doxorubicin (DOX). The Fenton-like reaction catalyzed by Mn2+ was amplified by both H2S and DOX, producing a mass of cytotoxic ·OH radicals. Through the combined action of gas therapy (GT), CDT, and chemotherapy, oxidative stress would be synergistically enhanced, inducing irreversible DNA damage and cell cycle arrest, eventually resulting in cancer cell apoptosis.

Characterized profiles of gut microbiota in morphine abstinence-induced depressive-like behavior.

Morphine is the most widely used analgesic for pain management worldwide. Abstinence of morphine could lead to neuropsychiatric symptoms, including depression. Gut microbiota is believed to contribute to the development of depression. However, the characteristics and potential role of gut microbiota in morphine abstinence-induced depression remain unclear. In the present study, we first established morphine abstinence-induced depressive behavior in mice. After dividing the mice into depressive and non-depressive groups, the gut microbiota of the mice was detected by 16S rRNA gene sequencing. The difference in the diversities and abundance of the gut microbiota were analyzed between groups. Then, the representative microbial markers that could distinguish each group were identified. In addition, gene function prediction of the operational taxonomic units (OTUs) with differential abundance between the depressive and non-depressive groups after morphine abstinence was conducted. Our results suggested that four weeks of abstinence from morphine did not change the richness of the gut microbiota. However, morphine abstinence influenced the gut microbial composition. Several specific genera of gut microbiota were identified as markers for each group. Interestingly, gene function prediction found that the fatty acid metabolism pathway was enriched in the OUTs in the depressive group compared with the non-depressive group after morphine abstinence. Our data suggested that gut microbiota dysbiosis was associated with morphine abstinence-induced depressive behavior, possibly by implicating the fatty acid metabolism pathway.

Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting Functions.

The development of biocompatible and nontoxic surface-enhanced Raman scattering (SERS) nanoparticles is of considerable current interest because of their attractive biomedical applications such as ultrasensitive in vitro diagnostics, in vivo tumor imaging, and spectroscopy-guided cancer surgery. However, current SERS nanoparticles are prepared and stored in aqueous solution, have limited stability and dispersibility, and are not suitable for lyophilization and storage by freeze-drying or other means. Here, we report a simple but robust method to coat colloidal SERS nanoparticles by naturally derived biomimetic red blood cell membranes (RBCM), leading to a dramatic improvement in stability and dispersibility under freeze-thawing, lyophilization, heating, and physiological conditions. The results demonstrate that the lyophilized SERS nanoparticles in the solid form can be readily dissolved and dispersed in physiological buffer solutions. A surprising finding is that the RBCM-coated SERS particles are considerably brighter (by as much as 5-fold) than PEGylated SERS particles under similar experimental conditions. This additional enhancement is believed to arise from the hydrophobic nature of RBCM's hydrocarbon chains, which is known to reduce electronic dampening and boost electromagnetic field enhancement. A further advantage in using biomimetic membrane coatings is that the bilayer membrane structure allows nonvalent insertion of molecular ligands for tumor targeting. In particular, we show that cyclic-RGD, a tumor-targeting peptide, can be efficiently inserted into the membrane coatings of SERS nanoparticles for targeting the ανß3 integrin receptors expressed on cancer cells. Thus, biomimetic RBCMs provide major advantages over traditional polyethylene glycols for preparing SERS nanoparticles with improved dispersibility, higher signal intensity, and more efficient biofunctionalization.

Accelerated Digital Biodetection Using Magneto-plasmonic Nanoparticle-Coupled Photonic Resonator Absorption Microscopy.

Rapid, ultrasensitive, and selective quantification of circulating microRNA (miRNA) biomarkers in body fluids is increasingly deployed in early cancer diagnosis, prognosis, and therapy monitoring. While nanoparticle tags enable detection of nucleic acid or protein biomarkers with digital resolution and subfemtomolar detection limits without enzymatic amplification, the response time of these assays is typically dominated by diffusion-limited transport of the analytes or nanotags to the biosensor surface. Here, we present a magnetic activate capture and digital counting (mAC+DC) approach that utilizes magneto-plasmonic nanoparticles (MPNPs) to accelerate single-molecule sensing, demonstrated by miRNA detection via toehold-mediated strand displacement. Spiky Fe3O4@Au MPNPs with immobilized target-specific probes are "activated" by binding with miRNA targets, followed by magnetically driven transport through the bulk fluid toward nanoparticle capture probes on a photonic crystal (PC). By spectrally matching the localized surface plasmon resonance of the MPNPs to the PC-guided resonance, each captured MPNP locally quenches the PC reflection efficiency, thus enabling captured MPNPs to be individually visualized with high contrast for counting. We demonstrate quantification of the miR-375 cancer biomarker directly from unprocessed human serum with a 1 min response time, a detection limit of 61.9 aM, a broad dynamic range (100 aM to 10 pM), and a single-base mismatch selectivity. The approach is well-suited for minimally invasive biomarker quantification, enabling potential applications in point-of-care testing with short sample-to-answer time.

Emergence of two near-infrared windows for in vivo and intraoperative SERS.

Two clear windows in the near-infrared (NIR) spectrum are of considerable current interest for in vivo molecular imaging and spectroscopic detection. The main rationale is that near-infrared light can penetrate biological tissues such as skin and blood more efficiently than visible light because these tissues scatter and absorb less light at longer wavelengths. The first clear window, defined as light wavelengths between 650nm and 950nm, has been shown to be far superior for in vivo and intraoperative optical imaging than visible light. The second clear window, operating in the wavelength range of 1000-1700nm, has been reported to further improve detection sensitivity, spatial resolution, and tissue penetration because tissue photon scattering and background interference are further reduced at longer wavelengths. Here we discuss recent advances in developing biocompatible plasmonic nanoparticles for in vivo and intraoperative surface-enhanced Raman scattering (SERS) in both the first and second NIR windows. In particular, a new class of 'broad-band' plasmonic nanostructures is well suited for surface Raman enhancement across a broad range of wavelengths allowing a direct comparison of detection sensitivity and tissue penetration between the two NIR window. Also, optimized and encoded SERS nanoparticles are generally nontoxic and are much brighter than near-infrared quantum dots (QDs), raising new possibilities for ultrasensitive detection of microscopic tumors and image-guided precision surgery.

Angle-independent pH-sensitive composites with natural gyroid structure.

pH sensor is an important and practical device with a wide application in environmental protection field and biomedical industries. An efficient way to enhance the practicability of intelligent polymer composed pH sensor is to subtilize the three-dimensional microstructure of the materials, adding measurable features to visualize the output signal. In this work, C. rubi wing scales were combined with pH-responsive smart polymer polymethylacrylic acid (PMAA) through polymerization to achieve a colour-tunable pH sensor with nature gyroid structure. Morphology and reflection characteristics of the novel composites, named G-PMAA, are carefully investigated and compared with the original biotemplate, C. rubi wing scales. The most remarkable property of G-PMAA is a single-value corresponding relationship between pH value and the reflection peak wavelength (λmax), with a colour distinction degree of 18 nm/pH, ensuring the accuracy and authenticity of the output. The pH sensor reported here is totally reversible, which is able to show the same results after several detection circles. Besides, G-PMAA is proved to be not influenced by the detection angle, which makes it a promising pH sensor with superb sensitivity, stability, and angle-independence.

Hydrothermal Synthesis Au-Bi2Te3 Nanocomposite Thermoelectric Film with a Hierarchical Sub-Micron Antireflection Quasi-Periodic Structure.

In this work, Au-Bi(2)Te(3) nanocomposite thermoelectric film with a hierarchical sub-micron antireflection quasi-periodic structure was synthesized via a low-temperature chemical route using Troides helena (Linnaeus) forewing (T_FW) as the biomimetic template. This method combines chemosynthesis with biomimetic techniques, without the requirement of expensive equipment and energy intensive processes. The microstructure and the morphology of the Au-Bi(2)Te(3) nanocomposite thermoelectric film was analyzed by X-ray diffraction (XRD), field-emission scanning-electron microscopy (FESEM), and transmission electron microscopy (TEM). Coupled the plasmon resonances of the Au nanoparticles with the hierarchical sub-micron antireflection quasi-periodic structure, the Au-Bi(2)Te(3) nanocomposite thermoelectric film possesses an effective infrared absorption and infrared photothermal conversion performance. Based on the finite difference time domain method and the Joule effect, the heat generation and the heat source density distribution of the Au-Bi(2)Te(3) nanocomposite thermoelectric film were studied. The heterogeneity of heat source density distribution of the Au-Bi(2)Te(3) nanocomposite thermoelectric film opens up a novel promising technique for generating thermoelectric power under illumination.

A highly sensitive room temperature H2S gas sensor based on SnO2 multi-tube arrays bio-templated from insect bristles.

A tin oxide multi-tube array (SMTA) with a parallel effect was fabricated through a simple and promising method combining chemosynthesis and biomimetic techniques; a biomimetic template was derived from the bristles on the wings of the Alpine Black Swallowtail butterfly (Papilio maackii). SnO2 tubes are hollow and porous structures with micro-pores regularly distributed on the wall. The morphology, the delicate microstructure and the crystal structure of this SMTA were characterized by super resolution digital microscopy, scanning electron microscopy, transmission electron microscopy and X-ray diffraction. The SMTA exhibits a high sensitivity to H2S gas at room temperature. It also exhibits a short response/recovery time, with an average value of 14/30 s at 5 ppm. In particular, heating is not required for the SMTA in the gas sensitivity measurement process. On the basis of these results, SMTA is proposed as a suitable new material for the design and fabrication of room-temperature H2S gas sensors.