Food-borne bacteria analysis using a diatomite bioinspired SERS platform.

Rapid and sensitive detection of food-borne bacteria has remained challenging over the past few decades. We propose a surface-enhanced Raman scattering sensing strategy based on a novel bioinspired surface-enhanced Raman scattering substrate, which can directly detect dye molecular residues and food-borne pathogen microorganisms in the environment. The surface-enhanced Raman scattering platform consists of a natural diatomite microporous array decorated with a metal-phenolic network that enables the in situ reduction of gold nanoparticles. The as-prepared nanocomposites display excellent surface-enhanced Raman scattering activity with the lowest limit of detection and the maximum Raman enhancement factor of dye molecules up to 10-11 M and 1.18 × 107, respectively. For food-borne bacterial detection, a diatomite microporous array decorated with a metal polyphenol network and gold nanoparticle-based surface-enhanced Raman scattering analysis is capable of distinguishing the biochemical fingerprint information of Staphylococcus aureus and Escherichia coli, indicating the great potential for strain identification.

Label-Free Surface-Enhanced Raman Scattering Bioanalysis Based on Au@Carbon Dot Nanoprobes.

Surface-enhanced Raman scattering (SERS) technology has attracted more and more attention in the biomedical field due to its ability to provide molecular fingerprint information of biological samples, as well as its potential in single-cell analysis. This work aims to establish a simple strategy for label-free SERS bioanalysis based on Au@carbon dot nanoprobes (Au@CDs). Here, polyphenol-derived CDs are utilized as the reductant to rapidly synthesize core-shell Au@CD nanostructures, which allows powerful SERS performance even when the concentration of methylene blue (MB) is as low as 10-9 M, due to the cooperative Raman enhancement mechanism. For bioanalysis, Au@CDs can serve as a unique SERS nanosensor to identify the cellular components of biosamples (e.g., cancer cells and bacteria). The molecular fingerprints from different species can be further distinguished after combination with the principal component analysis. In addition, Au@CDs also enable label-free SERS imaging to analyze intracellular composition profiles. This strategy offers a feasible, label-free SERS bioanalysis, opening up a new prospect for nanodiagnosis.

In situ photothermal nano-vaccine based on tumor cell membrane-coated black phosphorus-Au for photo-immunotherapy of metastatic breast tumors.

Cancer vaccines which can activate antitumor immune response have great potential for metastatic tumors treatment. However, clinical translation of cancer vaccines remained challenging due to weak tumor antigen immunogenicity, inefficient in vivo delivery, and immunosuppressive tumor microenvironment. Nanomaterials-based photothermal treatment (PTT) triggers immunogenic cell death while providing in situ tumor-associated antigens for subsequent anti-tumor immunity. Here, an in situ photothermal nano-vaccine (designated as BCNCCM) based on cancer cell membrane (CCM) was explored by co-encapsulating immune adjuvant CpG oligodeoxynucleotide (ODN) loaded black phosphorus-Au (BP-Au) nanosheets together with an indoleamine 2,3-dioxygenase (IDO) inhibitor (NLG919) by CCM, for the elimination of primary and metastatic breast tumors. The nano-vaccine could be delivered to tumor site selectively by CCM targeting and exhibit vaccine-like functions through the combined effect of in situ generated tumor-associate agents after PTT and immune adjuvant CpG, resulting in trigger of tumor-specific immunity. Furthermore, tumor inhibition was enhanced owing to the reversed immunosuppressive microenvironment mediated by IDO inhibitors. The nano-vaccine not only had good therapeutic effect on primary and metastatic tumors, but also could prevent tumor recurrence by producing systemic immune memory. Therefore, the photothermal nano-vaccine which coordinate in situ vaccine-like function and immune modulation may be a promising stragegy for photo-immunotherapy of metastatic tumors.

NIR-II Responsive Molybdenum Dioxide Nanosystem Manipulating Cellular Immunogenicity for Enhanced Tumor Photoimmunotherapy.

Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has emerged as a better candidate for deep-tissue tumor elimination. More interestingly, the photothermal ablated tumor cells also manifest somewhat immunostimulation potency to elicit antitumor immunity, although most dying cells are undergoing apoptosis that is commonly considered as immunologically silent. Here, a NIR-II responsive nanosystem is established for tumor photoimmunotherapy using molybdenum dioxide (MoO2) nanodumbbells as the nanoconverter. Meanwhile, an apoptosis-blocking strategy is proposed to regulate the cell death pattern under NIR-II laser irradiation in order to improve the immunogenic cell death. The nanoformulation can efficiently block caspase 8-dependent apoptotic pathway in photothermal ablated tumor cells and transform into more immunogenic death patterns, thereby activating systemic immunity to inhibit tumor growth and metastasis. In addition, this strategy also helps enhance the body's responses to α-PD-1 immune checkpoint inhibitor, which implies a potential optimal combination for cancer immunotherapy.

Carbon Dots with Intrinsic Bioactivities for Photothermal Optical Coherence Tomography, Tumor-Specific Therapy and Postoperative Wound Management.

Carbon dots (CDs) are considered as promising candidates with superior biocompatibilities for multimodel cancer theranostics. However, incorporation of exogenous components, such as targeting molecules and chemo/photo therapeutic drugs, is often required to improve the therapeutic efficacy. Herein, an "all-in-one" CDs that exhibit intrinsic bioactivities for bioimaging, potent tumor therapy, and postoperative management is proposed. The multifunctional CDs derived from gallic acid and tyrosine (GT-CDs) consist of a graphitized carbon core and N, O-rich functional groups, which endow them with a high near-infrared (NIR) photothermal conversion efficiency of 33.9% and tumor-specific cytotoxicity, respectively. A new imaging modality, photothermal optical coherence tomography, is introduced using GT-CDs as the contrast agent, offering the micrometer-scale resolution 3D tissue morphology of tumor. For cancer therapy, GT-CDs initiate the intracellular generation of reactive oxygen species in tumor cells but not normal cells, further induce the mitochondrial collapse and subsequent tumor cellular apoptosis. Combined with NIR photothermal treatment, synergistic antitumor therapy is achieved in vitro and in vivo. GT-CDs also promote the healing process of bacteria-contaminated skin wound, demonstrating their potential to prevent postoperative infection. The integrated theranostic strategy based on versatile GT-CDs supplies an alternative easy-to-handle pattern for disease management.

Dual-responsive ultrathin 1T-phase niobium telluride nanosheet-based delivery systems for enhanced chemo-photothermal therapy.

1T-phase niobium telluride (NbTe2) nanosheets are becoming increasingly important in emerging fields, such as spintronics, sensors and magneto-optoelectronics, due to their excellent physical and chemical properties. However, exploration on their biomedical applications are limited. Herein, ultrathin 1T-phase NbTe2 single-crystalline nanosheets with excellent photothermal performance, high drug-loading rate, near-infrared (NIR) light/acidic pH-triggered drug release, and low toxicity were developed for potentiated photothermal therapy. Importantly, they showed excellent biocompatibility in vivo and in vitro. NbTe2 nanosheets loaded with integrated stress response inhibitors (ISRIB) could achieve chemo-photothermal therapy of tumors through the ATF4-ASNS signaling axis. Ultrathin 1T-phase NbTe2 single-crystalline nanosheets with unique photothermal properties, drug loading rate and safety provide dramatic possibilities in biomedical applications, such as tissue imaging, photothermal therapeutics and pharmaceutics.

Redox responsive nanoparticle encapsulating black phosphorus quantum dots for cancer theranostics.

Effective cancer treatment puts high demands for cancer theranostics. For cancer diagnostics, optical coherence tomography (OCT) technology (including photothermal optical coherence tomography (PT-OCT)) has been widely investigated since it induces changes in optical phase transitions in tissue through environmental changes (such as temperature change for PT-OCT). In this report, redox responsive nanoparticle encapsulating black phosphorus quantum dots was developed as a robust PT-OCT agent. Briefly, black phosphorus quantum dots (BPQDs) are incorporated into cysteine-based poly-(disulfide amide) (Cys-PDSA) to form stable and biodegradable nanoagent. The excellent photothermal feature allows BPQD/Cys-PDSA nanoparticles (NPs) as a novel contrast agent for high-resolution PT-OCT bioimaging. The Cys-PDSA can rapidly respond to glutathione and effectively release BPQDs and drugs in vitro and in vivo. And the obtained NPs exhibit excellent near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity that can serve as novel therapeutic platform, with very low chemo drug dosage and side effects. Both of the polymer and BPQD are degradable, indicating this platform is a rare PT-OCT agent that is completely biodegradable. Overall, our research highlights a biodegradable and biocompatible black phosphorus-based nanoagent for both cancer diagnosis and therapy.

Photo-induced synthesis of molybdenum oxide quantum dots for surface-enhanced Raman scattering and photothermal therapy.

By means of a simple and photo-induced method, four colors of molybdenum oxide quantum dots (MoOx QDs) have been synthesized, using Mo(CO)6 as the structural guiding agent and molybdenum source. The as-prepared MoOx QDs display diverse optical properties due to the different configurations of oxygen vacancies in various nanostructures. Among them, crystalline molybdenum dioxide (MoO2) with a deep blue color shows the most intense localized surface plasmon resonance effect in the near-infrared (NIR) region. The strong NIR absorption endows MoO2 QDs with a high photothermal conversion efficiency of 66.3%, enabling broad prospects as a photo-responsive nanoagent for photothermal therapy of cancer. Moreover, MoO2 QDs can also serve as a novel semiconductor substrate for ultrasensitive surface-enhanced Raman scattering (SERS) analysis of aromatic molecules, amino acids and antibiotics, with SERS performance comparable to that of noble metal-based substrates. The therapeutic applications of MoO2 QDs open up a new avenue for tumor nanomedicine.

SERS analysis of carcinoma-associated fibroblasts in a tumor microenvironment based on targeted 2D nanosheets.

Carcinoma-associated fibroblasts (CAFs), one of the most important components of a tumor microenvironment (TME), play a significant role in the complex tumorigenesis process. Herein, the evolution of CAFs in TME is elaborately investigated by surface-enhanced Raman spectroscopy (SERS), a molecular fingerprint technique. Two-dimensional (2D) nanocomposites consisting of gold nanoparticles and a supramolecular "PCsheet" self-assembled between 2D nanosheets and oxidized phosphatidylcholine (PC) are fabricated as SERS-active probes to specifically recognize the CD36 receptor on the cytomembrane of the fibroblasts, a reliable landmark of CAF development. The 2D SERS substrates can also illuminate the fingerprint information around the CD36 protein with high detection sensitivity, which helps elucidate the biochemical component transition in the protein mini-domain during carcinoma progression. Visualized data are then supplied by label-free SERS imaging to exploit the distribution of biomolecules on the plasma membrane. In addition, the repressed expression of CD36 in TME is detected in lung metastasis tumor-bearing mice. This study based on the 2D SERS technique opens up an alternative avenue for unveiling carcinoma-associated molecular events.

Biodegradable Black Phosphorus-based Nanomaterials in Biomedicine: Theranostic Applications.

Ascribe to the unique two-dimensional planar nanostructure with exceptional physical and chemical properties, black phosphorous (BP) as the emerging inorganic twodimensional nanomaterial with high biocompatibility and degradability has been becoming one of the most promising materials of great potentials in biomedicine. The exfoliated BP sheets possess ultra-high surface area available for valid bio-conjugation and molecular loading for chemotherapy. Utilizing the intrinsic near-infrared optical absorbance, BPbased photothermal therapy in vivo, photodynamic therapy and biomedical imaging has been realized, achieving unprecedented anti-tumor therapeutic efficacy in animal experiments. Additionally, the BP nanosheets can strongly react with oxygen and water, and finally degrade to non-toxic phosphate and phosphonate in the aqueous solution. This manuscript aimed to summarize the preliminary progresses on theranostic application of BP and its derivatives black phosphorus quantum dots (BPQDs), and discussed the prospects and the state-of-art unsolved critical issues of using BP-based material for theranostic applications.

A two-dimensional fingerprint nanoprobe based on black phosphorus for bio-SERS analysis and chemo-photothermal therapy.

Flake-shaped nanohybrids based on black phosphorus (BP) have been developed as multifunctional theranostic nanoplatforms for drug delivery, phototherapy and bioimaging. In this work, we report a facile strategy for fabrication of black phosphorus-Au nanoparticle hybrids (BP-AuNPs), which reveal an extraordinary near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity. The applications of the nanocomposites as therapeutic agents for high-performance chemo-photothermal tumor therapy are accomplished in vitro and in vivo. BP-AuNPs also exhibit wonderful surface-enhanced Raman scattering (SERS) activity under NIR laser excitation with a low Raman background, allowing BP-AuNPs to be used as a promising two-dimensional (2D) fingerprint nanoprobe for bio-SERS analysis. The cellular component identification and label-free live-cell bioimaging based on this type of 2D SERS substrate are generally investigated, which open up promising new perspectives in nanomedicine, including diagnosis, imaging and therapy.

Effect of Red Light-Emitting Diodes Irradiation on Hemoglobin for Potential Hypertension Treatment Based on Confocal Micro-Raman Spectroscopy.

Red light-emitting diodes (LED) were used to irradiate the isolated hypertension hemoglobin (Hb) and Raman spectra difference was recorded using confocal micro-Raman spectroscopy. Differences were observed between the controlled and irradiated Hb by comparing the spectra records. The Raman spectrum at the 1399 cm-1 band decreased following prolonged LED irradiation. The intensity of the 1639 cm-1 band decreased dramatically in the first five minutes and then gradually increased in a time-dependent manner. This observation indicated that LED irradiation increased the ability of oxygen binding in Hb. The appearance of the heme aggregation band at 1399 cm-1, in addition to the oxygen marker band at 1639 cm-1, indicated that, in our study, 30 min of irradiation with 15.0 mW was suitable for inhibiting heme aggregation and enhancing the oxygen-carrying capacity of Hb. Principal component analysis showed a one-to-one relationship between irradiated Hb at different time points and the corresponding Raman spectra. Our approach could be used to analyze the hemoglobin from patients with confocal micro-Raman spectroscopy and is helpful for developing new nondrug hypertension therapy.

Synthesis of Au NP@MoS2 Quantum Dots Core@Shell Nanocomposites for SERS Bio-Analysis and Label-Free Bio-Imaging.

In this work, we report a facile method using MoS2 quantum dots (QDs) as reducers to directly react with HAuCl4 for the synthesis of Au nanoparticle@MoS2 quantum dots (Au NP@MoS2 QDs) core@shell nanocomposites with an ultrathin shell of ca. 1 nm. The prepared Au NP@MoS2 QDs reveal high surface enhanced Raman scattering (SERS) performance regarding sensitivity as well as the satisfactory SERS reproducibility and stability. The limit of detection of the hybrids for crystal violet can reach 0.5 nM with a reasonable linear response range from 0.5 µM to 0.5 nM (R² ≈ 0.974). Furthermore, the near-infrared SERS detection based on Au NP@MoS2 QDs in living cells is achieved with distinct Raman signals which are clearly assigned to the various cellular components. Meanwhile, the distinguishable SERS images are acquired from the 4T1 cells with the incubation of Au NP@MoS2 QDs. Consequently, the straightforward strategy of using Au NP@MoS2 QDs exhibits great potential as a superior SERS substrate for chemical and biological detection as well as bio-imaging.

Multifunctional Nanoplatform Based on Black Phosphorus Quantum Dots for Bioimaging and Photodynamic/Photothermal Synergistic Cancer Therapy.

A multifunctional nanoplatform based on black phosphorus quantum dots (BPQDs) was developed for cancer bioimaging and combined photothermal therapy (PTT) and photodynamic therapy (PDT). BPQDs were functionalized with PEG chains to achieve improved biocompatibility and physiological stability. The as-prepared nanoparticles exhibite prominent near-infrared (NIR) photothermal and red-light-triggered photodynamic properties. The combined therapeutic application of PEGylated BPQDs were then performed in vitro and in vivo. The results demonstrate that the combined phototherapy significantly promote the therapeutic efficacy of cancer treatment in comparison with PTT or PDT alone. BPQDs could also serve as the loading platform for fluorescent molecules, allowing reliable imaging of cancer cells. In addition, the low cytotoxicity and negligible side effects to main organs were observed in toxicity experiments. The theranostic characteristics of PEGylated BPQDs provide an uplifting potential for the future clinical applications.

Effects of different-intensity laser acupuncture at two adjacent same-meridian acupoints on nitric oxide and soluble guanylate cyclase releases in human.

OBJECTIVES: The aim of this study was to detect the influences of LA at nonacupoint and two adjacent acupoints of pericardium meridian on the releases of NO and sGC in 20 healthy subjects. METHODS: Different intensities (12, 24, 48 mW) of infrared laser were used for irradiating Jianshi (PC5), Ximen (PC4) acupoints and nonacupoint for 20, 40 minutes, respectively. Semi-circular tubes were taped to the skin surface and filled with NO-scavenging compound for 20 minutes to capture NO and sGC, which were measured using spectrophotometry in a blinded fashion. RESULTS: As the increase in the intensity of LA stimulation, the levels of NO releases over acupoints all were significantly increased, NO releases in nonacupoints following the same treatment only changed slightly, sGC amounts were observably enhanced over acupoints, but did not any change in nonacupoint area. Different intensities of LA treatments can sensitively affect the NO and sGC releases over acupoints. This indicated that LA-induced releases of the NO and sGC were specific to acupoints. CONCLUSIONS: This is the first evidence reporting that LA induced significant elevations of NO-sGC releases over acupoints, and the enhanced signal molecules contribute to local circulation, which improves the beneficial effects of the therapy.

Facile synthesis of black phosphorus-Au nanocomposites for enhanced photothermal cancer therapy and surface-enhanced Raman scattering analysis.

Black phosphorus (BP), a new type of two-dimensional nanomaterial, has attracted crucial attention in recent years owing to its excellent properties and great potential in various chemical, physical, and biological fields. In this study, BP nanosheets loaded with Au nanoparticles (BP-Au NSs) are obtained by a one-step facile synthetic method. The Au nanostructures can not only enhance the photothermal efficiency of the nanocomposites, but also endow BP-Au NSs with the potential to act as effective surface-enhanced Raman scattering (SERS) substrates for Raman biodetection. Cancer photothermal therapy (PTT) has been carried out in vitro and in vivo using BP-Au NSs as nanoagents. Under irradiation by an 808 nm laser, BP-Au NSs are capable of producing sufficient hyperthermia to destroy cancer cells, and the transplanted tumors in most of the tumor-bearing mice disappeared; BP-Au NSs are more effective than bare BP nanosheets. The PTT effect can also be monitored by a Raman technique that benefits from the high SERS activity of the BP-Au NSs. The molecular fingerprint features of breast tumors before and after PTT treatment were clearly identified using SERS analysis. The theranostic applications of BP-Au NSs exhibit promising potential in biomedicine.

Biological pH sensing based on the environmentally friendly Raman technique through a polyaniline probe.

The biological pH plays an important role in various cellular processes. In this work, a novel strategy is reported for biological pH sensing by using Raman spectroscopy and polyaniline nanoparticles (PANI NPs) as the pH-sensitive Raman probe. It is found that the Raman spectrum of PANI NPs is strongly dependent on the pH value. The intensities of Raman spectral bands at 1225 and 1454 cm-1 increase obviously with pH value varying from 5.5 to 8.0, which covers the range of regular biological pH variation. The pH-dependent Raman performance of PANI NPs, as well as their robust Raman signals and sensitivities to pH, was well retained after the nanoparticles incorporated into living 4T1 breast adenocarcinoma cells. The data indicate that such PANI NPs can be used as an effective biological pH sensor. Most interestingly, the PANI spherical nanostructures can be acquired by a low-cost, metal-free, and one-pot oxidative polymerization, which gives them excellent biocompatibility for further biological applications.

Fabrication of Graphene and AuNP Core Polyaniline Shell Nanocomposites as Multifunctional Theranostic Platforms for SERS Real-time Monitoring and Chemo-photothermal Therapy.

In this work, novel theranostic platforms based on graphene oxide and AuNP core polyaniline shell (GO-Au@PANI) nanocomposites are fabricated for simultaneous SERS imaging and chemo-photothermal therapy. PANI, a new NIR photothermal therapy agent with strong NIR absorption, outstanding stability and low cytotoxicity is decorated on AuNPs by one-pot oxidative polymerization, then the Au@PANI core-shell nanoparticles are attached to the graphene oxide (GO) sheet via π-π stacking and electrostatic interaction. The obtained GO-Au@PANI nanohybirds exhibit excellent NIR photothermal transduction efficiency and ultrahigh drug-loading capacity. The nanocomposites can also serve as novel NIR SERS probes utilizing the intense SERS signals of PANI. Rapid SERS imaging of cancer cells is achieved using this ultrasensitive nanoprobe. GO-Au@PANI also reveals good capability of drug delivery with the DOX-loading efficiency of 189.2% and sensitive NIR/pH-responsive DOX release. The intracellular real-time drug release dynamics from the nanocomposites is monitored by SERS-fluorescence dual mode imaging. Finally, chemo-photothermal ablation of cancer cells is carried out in vitro and in vivo using GO-Au@PANI as high-performance chemo-photothermal therapeutic nanoagent. The theranostic applications of GO-Au@PANI endow it with great potential for personalized and precise cancer medicine.

In vitro and in vivo brain-targeting chemo-photothermal therapy using graphene oxide conjugated with transferrin for Gliomas.

Current therapies for treating malignant glioma exhibit low therapeutic efficiency because of strong systemic side effects and poor transport across the blood brain barrier (BBB). Herein, we combined targeted chemo-photothermal glioma therapy with a novel multifunctional drug delivery system to overcome these issues. Drug carrier transferrin-conjugated PEGylated nanoscale graphene oxide (TPG) was successfully synthesized and characterized. When loaded on the proposed TPG-based drug delivery (TPGD) system, the anticancer drug doxorubicin could pass through the BBB and improve drug accumulation both in vitro and in vivo. TPGD was found to perform dual functions in chemotherapy and photothermal therapy. Targeted TPGD combination therapy showed higher rates of glioma cell death and prolonged survival of glioma-bearing rats compared with single doxorubicin or PGD therapy. In conclusion, we developed a potential nanoscale drug delivery system for combined therapy of glioma that can effectively decrease side effects and improve therapeutic effects.

[Polypyrrole Functionalized Gold Nanorods as Novel Contrast Agents for Optical Coherence Tomography].

Polypyrrole (PPy) is easy-prepared with good biocompatibility and strong absorption in near-infrared (NIR) region which can serve as both the photothermal therapeutic agent and contrast agent of optical coherence tomography (OCT) imaging. Herein, gold nanorod (GNR) modified with PPy (GNR-PPy) as contrast agent for optical coherence tomography imaging was investigated. GNR-PPy was synthesized via one-pot facile oxidative polymerization by using pyrrole and GNR as starting materials. Nanoparticles were characterized using ultraviolet-visible absorbance spectroscopy, Raman spectroscopy and transmission electron microscopy. A xenograft tumor mouse model was fabricated to study the OCT contrast effect of GNR-PPy on breast tumor. An OCT system equipped with an 840 nm SLED was used for OCT imaging of the tumors injected with gold nanostructures. The experimental results indicated that the penetration depth of the OCT signals from tumors injected with GNR-PPy was lower than that from tumors injected with gold nanorods, which could be ascribed to the stronger light activity of GNR-PPy in NIR region. To quantitatively analyze the contrast effect, the attenuation coefficients were extracted from the OCT images of tumors injected with the nanostructures. In comparison with the attenuation coefficient extracted from the OCT images containing GNR, the attenuation coefficient of tumors injected with GNR-PPy was significant higher. It was concluded that gold nanorods modified with polypyrrole can enhance the light absorption in near-infrared much better, which would provide a possible detection means for enhancing the contrast effect of tumor tissues.