Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model

Parkinson’s disease (PD) is second most common neurodegenerative disorder worldwide. Although drugs and surgery can relieve the symptoms of PD, these therapies are incapable of fundamentally treating the disease. For PD patients, over-expression of α-synuclein (SNCA) leads to the death of dopaminergic neurons. This process can be prevented by suppressing SNCA over-expression through RNA interference. Here, we successfully synthesized gold nanoparticles (GNP) composites (CTS@GNP-pDNA-NGF) via the combination of electrostatic adsorption and photochemical immobilization, which could load plasmid DNA (pDNA) and target specific cell types. GNP was transfected into cells via endocytosis to inhibiting the apoptosis of PC12 cells and dopaminergic neurons. Simultaneously, GNP composites are also used in PD models in vivo, and it can successfully cross the blood-brain barrier by contents of GNP in the mice brain. In general, all the works demonstrated that GNP composites have good therapeutic effects for PD models in vitro and in vivo.     

Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem

Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway. Combinatorial photothermal effects and BRAF knockdown by FA-GNR-siBRAF effectively killed tumor cells through apoptosis, with enhanced efficiency than individual treatments. Therefore, the FA-GNR-siBRAF simultaneously induced BRAF gene silencing and photothermal effects which achieved synergistic efficacy in the treatment of melanoma, paving a new path for developing clinical treatment methods for melanoma.     

发热患者中γ干扰素释放实验QuantiFERON-TBGold In Tube不确定结果及影响因素

目的:探讨发热患者中γ干扰素释放实验Quanti FERON-TB Gold In-Tube(QFT-GIT)不确定结果及影响因素。方法:选择感染科因发热收治入院的病例,统计患者一般状况、实验室检查包括γ干扰素释放实验QFT-GIT,血常规、血清白蛋白、补体、降钙素原(PCT)、超敏C反应蛋白(hs-CRP)、乳酸脱氢酶(LDH)、血清铁蛋白(SF)等炎症指标,并进行统计学分析。结果:215例患者中,QFT试验阳性83例,阴性66例,不确定结果 66例。QFT-QIT不确定组患者年龄、SF及LDH水平显著高于QFT确定组(P 0. 01或P 0. 05),淋巴细胞计数及血清白蛋白、补体C3、C4水平显著低于确定结果组(P 0. 01或P 0. 05)。多因素回归分析显示发热患者中出现QFT不确定结果的独立危险因素有低蛋白血症(OR=1. 156,95%CI 1. 028～1. 299)、淋巴细胞减少(OR=6. 009,95%CI 2. 147～16. 817)、高白细胞计数(OR=0. 800,95%CI 0. 680～0. 941)。结论:发热患者中QFT-GIT不确定结果出现比例较高,尤其是在低蛋白血症、低淋巴细胞血症及炎症反应强烈的患者。     

梅毒螺旋体感染四种血清学检测方法的临床评价

目的探讨四种梅毒血清学实验诊断方法的准确性及在临床的应用价值。方法应用甲苯胺红不加热血清学试验（TRUST）、酶联免疫吸附试验（ELISA）和胶体金法检测518例性病科患者血清,并用梅毒螺旋体明胶颗粒凝集试验（TPPA）确认。结果 TRUST法灵敏度为58.18%,ELI SA法为99.37%、胶体金法为99.06%;TRUST法特异度为88.5%,ELI SA法为98.50%、胶体金法为100%。结论梅毒检测方法各有优缺点,应根据检验目的合理选用不同的试验方法。     

Influence of chitosan coating on the oral bioavailability of gold nanoparticles in rats

Gold nanoparticles are one of the most extensively investigated metallic nanoparticles for several applications. It is less toxic than other metallic nanolattices. The exceptional electrical and thermal conductivity of gold make it possible to be administered as non-invasive radiofrequency irradiation therapy that produces sufficient heat to kill tumor cells. Nanoparticles are generally administered intravenously instead of orally due to negligible oral absorption and cellular uptake. This study evaluated the oral bioavailability of gold nanoparticles coated with chitosan (C-AuNPs), a natural mucoadhesive polymer. We employed traditional method of evaluating bioavailability that involve estimation of maximum concentrations and area under the curve of 3?nm chitosan coated gold nanoparticles (C-AuNPs) in the rat plasma following intravenous and oral administrations (0.8?mg and 8?mg/kg body weight respectively). The oral bioavailability of C-AuNPs was found to be 2.46% (approximately 25 folds higher than polyethylene glycol (PEG) coated gold nanoparticles, reported earlier). These findings suggest that chitosan coating could be better than PEG coating for the enhancement of oral bioavailability of nanoparticles.     

Stability enhanced polyelectrolyte-coated gold nanorod-photosensitizer complexes for high/low power density photodynamic therapy

Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm² for 0.5 min; low light dose = 25 mW/cm² for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors.     

PEGylated PAMAM dendrimer–doxorubicin conjugate-hybridized gold nanorod for combined photothermal-chemotherapy

We prepared pH-sensitive drug–dendrimer conjugate-hybridized gold nanorod as a promising platform for combined cancer photothermal-chemotherapy under in vitro and in vivo conditions. Poly(ethylene glycol)-attached PAMAM G4 dendrimers (PEG–PAMAM) were first covalently linked on the surface of mercaptohexadecanoic acid-functionalized gold nanorod (MHA-AuNR), with subsequent conjugation of anti-cancer drug doxorubicin (DOX) to dendrimer layer using an acid-labile-hydrazone linkage to afford PEG–DOX–PAMAM–AuNR particles. The particles with a high PEG–PAMAM dendrimer coverage density (0.28 per nm² AuNR) showed uniform sizes and excellent colloidal stability. In vitro drug release studies demonstrated that DOX released from PEG–DOX–PAMAM–AuNR was negligible under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. The efficient intracellular acid-triggered DOX release inside of lysosomes was confirmed using confocal laser scanning microscopy analysis. Furthermore, the combined photothermal-chemo treatment of cancer cells using PEG–DOX–PAMAM–AuNR for synergistic hyperthermia ablation and chemotherapy was demonstrated both in vitro and in vivo to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of PEG–DOX–PAMAM–AuNR particles for cancer therapy.     

Regulation of human endothelial progenitor cell maturation by polyurethane nanocomposites

The mobilization and homing of endothelial progenitor cells (EPCs) are critical to the development of an antithrombotic cardiovascular prosthesis. Polyurethane (PU) with superior elasticity may provide a mechanical environment resembling that of the natural vascular tissues. The topographical cues of PU were maximized by making nanocomposites with a small amount of gold nanoparticles (AuNPs). The nanocomposites of PU-AuNPs (“PU-Au”) with a favorable response of endothelial cells were previously established. In the current study, the effect of PU and PU-Au nanocomposites on the behavior of human peripheral blood EPCs was investigated in vitro and in vivo. It was found that PU-Au promoted EPCs to become differentiated endothelial cells in vitro, confirmed by the increased expressions of CD31 and VEGF-R2 surface markers. The increased maturation of EPCs was significantly more remarkable on PU-Au, probably through the stromal derived factor 1α (SDF-1α)/CXCR4 signaling pathway. In vivo experiments showed that EPCs seeded on PU-Au coated catheters effectively reduced thrombosis by differentiation into endothelial cells. Surface endothelialization with CD31 and CD34 expression as well as intimal formation with α-SMA expression was significantly accelerated in the group receiving EPC-seeded PU-Au catheters. Moreover, the analysis of collagen deposition revealed a reduction of fibrosis in the group receiving EPC-seeded PU-Au catheters as compared to the other groups. These results suggest that EPCs engineered with a proper elastic substrate may provide unique endothelialization and antithrombogenic properties that benefit vascular tissue regeneration.     

Optimization of PAMAM-gold nanoparticle conjugation for gene therapy

The development of efficient and biocompatible non-viral vectors for gene therapy remains a great challenge, and exploiting the properties of both nanoparticle carriers and cationic polymers is an attractive approach. In this work, we have developed gold nanoparticle (AuNP) polyamidoamine (PAMAM) conjugates for use as non-viral transfection agents. AuPAMAM conjugates were prepared by crosslinking PAMAM dendrimers to carboxylic-terminated AuNPs via EDC and sulfo-NHS chemistry. EDC and sulfo-NHS have been utilized widely and in numerous applications such as amino acid coupling; however, their use in the coupling of PAMAM dendrimers to AuNPs presents new challenges to form effective and stable constructs for delivery that have not yet been examined. Enhanced colloidal stability and DNA condensation ability was established by probing two critical synthetic parameters: the reaction rate of the PAMAM crosslinking step, and the amine to carboxyl ratio. Based on this work, increasing the amine to carboxyl ratio during conjugation of PAMAM onto AuNPs yielded the optimal vector with respect to colloidal stability and transfection efficiency in vitro. AuPAMAM conjugates present attractive candidates for non-viral gene delivery due to their commercial availability, ease of fabrication and scale-up, high yield, high transfection efficiency and low cytotoxicity.