Different Bacterial Communities Involved in Peptide Decomposition between Normoxic and Hypoxic Coastal Waters

RGD peptides has been used to detect cell surface integrin and direct clinical effective therapeutic drug selection. Herein we report that a quick one step detection of cell surface marker that was realized by a specially designed NiFe-based magnetic biosensing cell chip combined with functionalized magnetic nanoparti- cles. Magnetic nanoparticles with 20-30 nm in diameter were prepared by coprecipitation and modified with RGD-4C, and the resultant RGD-functionalized magnetic nanoparticles were used for targeting cancer cells cul- tured on the NiFe-based magnetic biosensing chip and distinguish the amount of cell surface receptor-integrin. Cell lines such as Calu3, Hela, A549, CaFbr, HEK293 and HUVEC exhibiting different integrin expression were chosen as test samples. Calu3, Hela, HEK293 and HUVEC cells were successfully identified. This approach has advantages in the qualitative screening test. Compared with traditional method, it is fast, sensitive, low cost, easy-operative, and needs very little human intervention. The novel method has great potential in applications such as fast clinical cell surface marker detection, and diagnosis of early cancer, and can be easily extended to other biomedical applications based on molecular recognition

A multifunctional ribonuclease A-conjugated carbon dot cluster nanosystem for synchronous cancer imaging and therapy

Carbon dots exhibit great potential in applications such as molecular imaging and in vivo molecular tracking. However, how to enhance fluorescence intensity of carbon dots has become a great challenge. Herein, we report for the first time a new strategy to synthesize fluorescent carbon dots (C-dots) with high quantum yields by using ribonuclease A (RNase A) as a biomolecular templating agent under microwave irradiation. The synthesized RNase A-conjugated carbon dots (RNase A@C-dots) exhibited quantum yields of 24.20%. The fluorescent color of the RNase A@C-dots can easily be adjusted by varying the microwave reaction time and microwave power. Moreover, the emission wavelength and intensity of RNase A@C-dots displayed a marked excitation wavelength-dependent character. As the excitation wavelength alters from 300 to 500 nm, the photoluminescence (PL) peak exhibits gradually redshifts from 450 to 550 nm, and the intensity reaches its maximum at an excitation wavelength of 380 nm. Its Stokes shift is about 80 nm. Notably, the PL intensity is gradually decreasing as the pH increases, almost linearly dependent, and it reaches the maximum at a pH = 2 condition; the emission peaks also show clearly a redshift, which may be caused by the high activity and perfective dispersion of RNase A in a lower pH solution. In high pH solution, RNase A tends to form RNase A warped carbon dot nanoclusters. Cell imaging confirmed that the RNase A@C-dots could enter into the cytoplasm through cell endocytosis. 3D confocal imaging and transmission electron microscopy observation confirmed partial RNase A@C-dots located inside the nucleus. MTT and real-time cell electronic sensing (RT-CES) analysis showed that the RNase A@C-dots could effectively inhibit the growth of MGC-803 cells. Intra-tumor injection test of RNase A@C-dots showed that RNase A@C-dots could be used for imaging in vivo gastric cancer cells. In conclusion, the as-prepared RNase A@C-dots are suitable for simultaneous therapy and in vivo fluorescence imaging of nude mice loaded with gastric cancer or other tumors

HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future

Chiral Antioxidant-based Gold Nanoclusters Reprogram DNA Epigenetic Patterns

Epigenetic modifications sit ‘on top of’ the genome and influence DNA transcription, which can force a significant impact on cellular behavior and phenotype and, consequently human development and disease. Conventional methods for evaluating epigenetic modifications have inherent limitations and, hence, new methods based on nanoscale devices are needed. Here, we found that antioxidant (glutathione) chiral gold nanoclusters induce a decrease of 5-hydroxymethylcytosine (5hmC), which is an important epigenetic marker that associates with gene transcription regulation. This epigenetic change was triggered partially through ROS activation and oxidation generated by the treatment with glutathione chiral gold nanoclusters, which may inhibit the activity of TET proteins catalyzing the conversion of 5-methylcytosine (5mC) to 5hmC. In addition, these chiral gold nanoclusters can downregulate TET1 and TET2 mRNA expression. Alteration of TET-5hmC signaling will then affect several downstream targets and be involved in many aspects of cell behavior. We demonstrate for the first time that antioxidant-based chiral gold nanomaterials have a direct effect on epigenetic process of TET-5hmC pathways and reveal critical DNA demethylation patterns

Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy

Antibody-Drug Gold Nanoantennas with Raman Spectroscopic Fingerprints for in Vivo Tumour Theranostics

Inspired by the ability of SERS nanoantennas to provide an integrated platform to enhance disease targeting in vivo, we developed a highly sensitive probe for in vivo tumoral recognition with the capacity to target specific cancer biomarkers such as epidermal growth factor receptors (EGFR) on human cancer cells and xenograft tumour models. Here, we used ~90 nm gold nanoparticles capped by a Raman reporter, encapsulated and entrapped by larger polymers and a FDA antibody-drug conjugate –Cetuximab (Erbitux®) – that specifically targets EGFR and turns off a main signalling cascade for cancer cells to proliferate and survive. These drug/SERS gold nanoantennas present a high Raman signal both in cancer cells and in mice bearing xenograft tumours. Moreover, the Raman detection signal is accomplished simultaneously by extensive tumour growth inhibition in mice, making these gold nanoantennas ideal for cancer nanotheranostics, i.e. tumour detection and tumoral cell inhibition at the same time

Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the drug-loaded gold nanogels are spherical and exist in the size of 180 nm. The single and combinatorial toxicity effects of curcumin- and piperine-loaded Lignin-g-p (NIPAM-co-DMAEMA) gold nanogels were studied against U-251 MG GBM cells. A cytotoxicity analysis displayed anticancer properties. IC50 of curcumin- and piperine-loaded gold nanogels were recorded at 30 μM and 35 μM, respectively. Immunostaining and Western blot analysis confirmed the protein expression of caspase-3 and cleaved caspase-3 in cells treated with drug-loaded nanogels. Kinetic drug release revealed 86% release of hybrid curcumin–piperine from gold nanogel after 250 min at pH 4. Atomic absorption spectroscopic analysis confirmed that the drug-loaded nanogels have better internalization or association with the cancer cells than the GNPs or nano-gels alone. Morphological studies further confirmed that the curcumin and piperine nanogels penetrate the cells via endocytic pathways and induce caspase-3-related apoptosis. The experimental evidence shows the enhanced properties of combinatorial curcumin–piperine gold nanogels (IC50: 21 μM) to overcome the limitations of conventional chemotherapeutic treatments of glioma cells

Egg white-mediated green synthesis of silver nanoparticles with excellent biocompatibility and enhanced radiation effects on cancer cells

A simple, cost-effective, and environmentally friendly approach to the aqueous-phase synthesis of silver (Ag) nanoparticles was demonstrated using silver nitrate (AgNO3) and freshly extracted egg white. The bio-conjugates were characterized by UV-visible spectroscopy, transmission electron microscopy, Fourier transform infrared spectrometry, and dynamic light scattering. These results indicated that biomolecule-coated Ag nanoparticles are predominantly spherical in shape with an average size of 20 nm. The proteins of egg white, which have different functional groups, played important roles in reducing Ag+ and maintaining product attributes such as stability and dispersity. In vitro cytotoxicity assays showed that these Ag-protein bio-conjugates showed good biocompatibility with mouse fibroblast cell lines 3T3. Furthermore, X-ray irradiation tests on 231 tumor cells suggested that the biocompatible Ag-protein bio-conjugates enhanced the efficacy of irradiation, and thus may be promising candidates for use during cancer radiation therapy

RNA Nanoparticle for Treatment of Gastric Cancer

The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer