One-Step in Situ Synthesis of Polypeptide–Gold Nanoparticles Hybrid Nanogels and Their Application in Targeted Photoacoustic Imaging

Hybrid nanogels have been widely used as multifunctional drug delivery carriers and imaging probes for biomedical applications. Two triblock artificial polypeptides PC₁₀A and PC₁₀ARGD were biosynthesized to prepare hybrid nanogels. When the concentration of these polypeptides drops to less than 2% (<i>w</i>/<i>w</i>), they can form nanogels by self-assembly. The physical characteristics of nanogels, such as surface potential, size, and targeting domain are able to be tuned. Polypeptide–gold nanoparticles hybrid nanogels were in situ synthesized using PC₁₀A­(RGD) as templates and photoinitiator I-2959 under 365 nm UV light irradiation in one step. The results of the effect of gold ion concentration on synthesized gold nanoparticles in hybrid nanogels showed that the size and the concentration of gold nanoparticles in hybrid nanogel increased gradually with the increasing of gold ion concentration. The concentration of polypeptide has no obvious effect on the properties of gold nanoparticles in hybrid nanogels and only influences the size of the hybrid nanogels. The concentration of gold nanoparticles in hybrid nanogels increased with the increasing of irradiation time. In addition, the change of pH (3.0–7.0) did not affect the properties of the gold nanoparticles in the hybrid nanogels. Cytotoxicity results showed that hybrid nanogels were almost nontoxic to HeLa cells when the concentration of Au ion was below 0.72 mM. An arginine-glycine-aspartic acid motif could be introduced into the PC₁₀ARGD–gold nanoparticles hybrid nanogels to enhance efficient receptor-mediated endocytosis in α_<i>v</i>β₃ overexpressing HeLa cells as analyzed by photoacoustic imaging. These results indicate that such hybrid nanogels are promising to be used in biomedical applications

Polypeptide-Engineered Hydrogel Coated Gold Nanorods for Targeted Drug Delivery and Chemo-photothermal Therapy

A new hybrid nanogel system using polypetide-engineered coated gold nanorods has been developed for targeted drug delivery and tumor chemo-photothermal therapy. A triblock engineered polypeptide PC₁₀A­(RGD) was immobilized on the surface of gold nanorods by the electrostatic adsorption. The immobilized PC₁₀A­(RGD) formed hydrogel by self-assembly to load doxorubicin for chemotherapy. Coating polypeptide-engineering hydrogel on gold nanorods enhanced the stability in high-salt media and significantly reduced the cytotoxicity. An arginine-glycine-aspartic acid motif was introduced into the polypeptide on the surface of hybrid nanogels to promote cellular uptake through receptor-mediated endocytosis in α_<i>v</i>β₃ overexpressing HeLa cells. In addition, compared with single chemotherapy and near-infrared photothermal therapy, the combination therapy has a synergistic effect on the cancer cells. Thus, the chemo-photothermal therapy based on polypeptide-engineered hydrogel coated gold nanorods and doxorubicin is expected to have great potential impact on cancer therapy

Facile Synthesis of Gold Nanospheres Modified by Positively Charged Mesoporous Silica, Loaded with Near-Infrared Fluorescent Dye, for in Vivo X‑ray Computed Tomography and Fluorescence Dual Mode Imaging

We developed a simple and efficient method to synthesize a novel probe for both computed tomography (CT) and fluorescence imaging. Gold nanospheres were coated with positively charged mesoporous silica (Au@mSiO₂-TTA) using a one-pot method to cohydrolyze quaternary ammonium silane and tetraethyl orthosilicate. Subsequently, IR-783, a negatively charged and water-soluble near-infrared fluorescent dye, was electrostatically adsorbed into the silica shell. Transmission electron microscopy imaging, X-ray powder diffraction, and energy dispersive X-ray spectroscopy indicated that Au@mSiO₂-TTA had a clear core–shell structure, was monodisperse, had a large surface area (530 m²/g), and had a uniform pore size (2.2 nm). The mesoporous structure could effectively load fluorescent dye. After loading, the zeta potential of the nanoparticle dropped from 48 mV to 30 mV, and after additional modification with polyvinylpyrrolidone, it further reduced to 6 mV. Probe fluorescence was stable over time, and the probe was an effective CT contrast agent and as a near-infrared fluorescent probe. The half-life of the probe in the blood was 1.5 h, and the probe was mainly distributed in the spleen and liver 4 h after injection. Tissue sections showed that major organs were normal and without visible morphological changes, 6 days post injection, indicating the biocompatibility of the probe

Quantification of MicroRNA in a Single Living Cell via Ionic Current Rectification-Based Nanopore for Triple Negative Breast Cancer Diagnosis

Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA). Benefiting from the enzyme-free CHA amplification strategy, the detection limit of the nanopore sensor for miRNA-155 reaches 10 fM and the nanopore sensor is more adaptable to complex intracellular environments. With the nanopore sensor, the concentration of miRNA-155 in living single cells is quantified to realize the early diagnosis of triple-negative breast cancer (TNBC). Furthermore, the nanopore sensor can be applied in screening anticancer drugs by tracking the expression level of miRNA-155. This work provides an adaptive and universal method for quantitatively analyzing intracellular miRNAs, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level

The Self-Evaluation of a School. The Function, Role and Responsibilities of School Leadership when Creating Evaluation Methods

Centrum školského managementuFaculty of EducationPedagogická fakult

MOESM3 of A multifunctional targeting probe with dual-mode imaging and photothermal therapy used in vivo

Additional file 3 Video of in vivo PAI of same part of tumor on the nude mouse under 523 nm laser excitation

In Vivo Computed Tomography/Photoacoustic Imaging and NIR-Triggered Chemo–Photothermal Combined Therapy Based on a Gold Nanostar‑, Mesoporous Silica‑, and Thermosensitive Liposome-Composited Nanoprobe

Safe multifunctional nanoplatforms that have multiple therapeutic functions integrated with imaging capabilities are highly desired for biomedical applications. In this paper, targeted chemo–photothermal synergistic therapy and photoacoustic/computed tomography imaging of tumors were achieved by one novel multifunctional nanoprobe (GMS/DOX@SLB-FA); it was composed of a gold nanostar core and a doxorubicin (DOX)-loaded mesoporous silica shell (GMS), which was coated with a folic acid (FA)-modified thermosensitively supported lipid bilayer (SLB-FA) as a gatekeeper. The multifunctional probe had perfect dispersion and stability; 2.1 nm mesoporous pores and 208 nm hydration particle sizes were obtained. In vitro studies indicated that the drug-loaded probe had excellent ability to control the release of DOX, with 71.98 ± 2.52% cumulative release after laser irradiation, which was significantly higher than that of unirradiated control group. A survival rate of 72.75 ± 4.37% of HeLa cells at 57.75 μg/mL probe also demonstrated the low cytotoxicity of the targeted probe. Both in vitro and in vivo results showed that the probe could achieve targeted photoacoustic imaging of tumors because of the fact that the FA-modified probe could specifically recognize the overexpressed FA receptors on tumor cells; meanwhile, the probe could also achieve the chemo–photothermal synergistic therapy of tumors through controlling the drug release from mesoporous channels by a near-infrared laser. Therefore, the probe had great potential in the early diagnosis and treatment of cancer

Discovery of 5‑Cyano-6-phenylpyrimidin Derivatives Containing an Acylurea Moiety as Orally Bioavailable Reversal Agents against P‑Glycoprotein-Mediated Mutidrug Resistance

P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has become a major obstacle in successful cancer chemotherapy, which attracted much effort to develop clinically useful compounds to reverse MDR. Here, we designed and synthesized a novel series of derivatives with a 5-cyano-6-phenylpyrimidine scaffold and evaluated their potential reversal activities against MDR. Among these compounds, <b>55</b>, containing an acylurea appendage, showed the most potent activity in reversing paclitaxel resistance in SW620/AD300 cells. Further studies demonstrated <b>55</b> could increase accumulation of PTX, interrupt ABCB1-mediated Rh123 accumulation and efflux, stimulate ABCB1 ATPase activity, and especially have no effect on CYP3A4 activity, which avoid drug interaction caused toxicity. More importantly, <b>55</b> significantly enhanced the efficacy of PTX against the SW620/AD300 cell xenograft without obvious side effects for orally intake. Given all that, the pyrimidine-acylurea based ABCB1 inhibitor may be a promising lead in developing new efficacious ABCB1-dependent MDR modulator

Discovery of 5‑Cyano-6-phenylpyrimidin Derivatives Containing an Acylurea Moiety as Orally Bioavailable Reversal Agents against P‑Glycoprotein-Mediated Mutidrug Resistance

P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has become a major obstacle in successful cancer chemotherapy, which attracted much effort to develop clinically useful compounds to reverse MDR. Here, we designed and synthesized a novel series of derivatives with a 5-cyano-6-phenylpyrimidine scaffold and evaluated their potential reversal activities against MDR. Among these compounds, <b>55</b>, containing an acylurea appendage, showed the most potent activity in reversing paclitaxel resistance in SW620/AD300 cells. Further studies demonstrated <b>55</b> could increase accumulation of PTX, interrupt ABCB1-mediated Rh123 accumulation and efflux, stimulate ABCB1 ATPase activity, and especially have no effect on CYP3A4 activity, which avoid drug interaction caused toxicity. More importantly, <b>55</b> significantly enhanced the efficacy of PTX against the SW620/AD300 cell xenograft without obvious side effects for orally intake. Given all that, the pyrimidine-acylurea based ABCB1 inhibitor may be a promising lead in developing new efficacious ABCB1-dependent MDR modulator

Discovery of 5‑Cyano-6-phenylpyrimidin Derivatives Containing an Acylurea Moiety as Orally Bioavailable Reversal Agents against P‑Glycoprotein-Mediated Mutidrug Resistance

P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has become a major obstacle in successful cancer chemotherapy, which attracted much effort to develop clinically useful compounds to reverse MDR. Here, we designed and synthesized a novel series of derivatives with a 5-cyano-6-phenylpyrimidine scaffold and evaluated their potential reversal activities against MDR. Among these compounds, <b>55</b>, containing an acylurea appendage, showed the most potent activity in reversing paclitaxel resistance in SW620/AD300 cells. Further studies demonstrated <b>55</b> could increase accumulation of PTX, interrupt ABCB1-mediated Rh123 accumulation and efflux, stimulate ABCB1 ATPase activity, and especially have no effect on CYP3A4 activity, which avoid drug interaction caused toxicity. More importantly, <b>55</b> significantly enhanced the efficacy of PTX against the SW620/AD300 cell xenograft without obvious side effects for orally intake. Given all that, the pyrimidine-acylurea based ABCB1 inhibitor may be a promising lead in developing new efficacious ABCB1-dependent MDR modulator