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

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

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

PKA, Caspase 1 and HSP40 Induced Apoptosis under Fungi Starvation

To investigate the influence of starvation on the biochemical response of Aspergillus niger. The biochemical impact of starvation was determined by morphological observation, immunofluorescent analysis, High-performance liquid chromatography (HPLC) and western blot over 8 days. Results showed that starvation can inhibit fungi survival rate in a time-dependent manner. A. niger exhibited active responses to starvation such as secretion of some 40 kDa proteins to manage changes in water balance. Conidiophores disintegrated from lack of nutrient. The immunofluorescent analysis demonstrated elevated ROS accumulation in starved cells (PA. niger growth by inducing cell apoptosis

Biocompatibility of hydrophilic silica-coated CdTe quantum dots and magnetic nanoparticles

Fluorescent magnetic nanoparticles exhibit great application prospects in biomedical engineering. Herein, we reported the effects of hydrophilic silica-coated CdTe quantum dots and magnetic nanoparticles (FMNPs) on human embryonic kidney 293 (HEK293) cells and mice with the aim of investigating their biocompatibility. FMNPs with 150 nm in diameter were prepared, and characterized by high-resolution transmission electron microscopy and photoluminescence (PL) spectra and magnetometer. HEK293 cells were cultured with different doses of FMNPs (20, 50, and 100μ g/ml) for 1-4 days. Cell viability and adhesion ability were analyzed by CCK8 method and Western blotting. 30 mice were randomly divided into three groups, and were, respectively, injected via tail vein with 20, 60, and 100 μg FMNPs, and then were, respectively, raised for 1, 7, and 30 days, then their lifespan, important organs, and blood biochemical parameters were analyzed. Results show that the prepared water-soluble FMNPs had high fluorescent and magnetic properties, less than 50 μg/ml of FMNPs exhibited good biocompatibility to HEK293 cells, the cell viability, and adhesion ability were similar to the control HEK293 cells. FMNPs primarily accumulated in those organs such as lung, liver, and spleen. Lung exposed to FMNPs displayed a dose-dependent inflammatory response, blood biochemical parameters such as white blood cell count (WBC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), displayed significant increase when the FMNPs were injected into mice at dose of 100μg. In conclusion, FMNPs exhibit good biocompatibility to cells under the dose of less than 50 μg/ml, and to mice under the dose of less than 2mg/kg body weight. The FMNPs' biocompatibility must be considered when FMNPs are used for in vivo diagnosis and therapy

3D Plasmonic Ensembles of Graphene Oxide and Nobel Metal Nanoparticles with Ultrahigh SERS Activity and Sensitivity

We describe a comparison study on 3D ensembles of graphene oxide (GO) and metal nanoparticles (silver nanoparticles (AgNPs), gold nanoparticles (GNPs), and gold nanorods (GNRs)) for surface-enhanced Raman scattering (SERS) application. For the first time, GNRs were successfully assembled on the surfaces of GO by means of electrostatic interactions without adding any surfactant. The SERS properties of GO/AgNPs, GO/GNPs, and GO/GNRs were compared using 2-mercaptopyridine (2-Mpy) as probing molecule. We found that GO/AgNPs and GO/GNPs substrates are not suitable for detecting 2-Mpy due to the very strong π-π stacking interaction between the 2-Mpy molecules and sp2 carbon structure of GO. Conversely, the GO/GNRs substrates show ultrahigh SERS activity and sensitivity of 2-Mpy with the detection limit as low as ~10-15 M, which is ~2-3 orders of magnitude higher than that of the corresponding GNRs