Browsing by Issue Date, starting with "2014-07-30"
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- RGD-Modified dendrimers for drug encapsulation and targeted inhibition of tumor cellsPublication . Xuedan, He; Xiangyang, Shi; Tomás, Helena Maria Pires GasparIn this study, cyclic arginine-glycine-aspartic acid (RGD) peptide-modified amine-terminated generation 5 poly(amidoamine) (G5.NH2 PAMAM) dendrimers were prepared for the encapsulation of the anticancer drug doxorubicin (DOX) for targeted delivery to cancer cells overexpressing αvβ3 integrin cell surface receptors. First, the thiolated RGD peptide was linked to polyethylene glycol (PEG) via the bifunctional cross-linking reagent 6-maleimidohexanoic acid N-hydroxysuccinimide ester (MHS). Then a dendrimer modification process was performed in which the PEGylated RGD peptide and fluorescein isothiocyanate (FI) were covalently attached to the G5 dendrimers. This process was finally followed by acetylation of the remaining dendrimer terminal amines. The experimental results show that each G5.NHAc-FI-PEG-RGD dendrimer approximately encapsulated six DOX molecules. This formed complex is water soluble and stable. In vitro release studies proved that the multifunctional dendrimers facilitate a sustained release of DOX. More interesting, one-dimensional NMR and two-dimensional NMR were applied to investigate the interactions between dendrimers and DOX. Here, the impact of the environmental pH on the release rate of DOX from G5.NHAc-FI-PEG-RGD/DOX was fully studied. Furthermore, cell biological studies demonstrated that G5.NHAc-FI-PEG-RGD dendrimers have no cytotoxicity towards U87-MG cancer cells but that G5.NHAc-FI-PEG-RGD/DOX complexes have almost the same cytotoxicity as DOX alone. Moreover, due to the targeting ability of RGD, this dendrimer/drug system can also specifically target and display therapeutic efficacy to cancer cells overexpressing αvβ3 integrins. The cellular internalization of the multifunctionalized dendrimer was shown to be receptor mediated to an important extent. According to this study, we can say that G5.NHAc-FI-PEG-RGD is a promising system for the targeted therapy of different types of cancer.
- Solid phase extraction based on nanomaterials for isolation of urinary volatile metabolitesPublication . Zheng, Qiao; Câmara, José de Sousa; Rodrigues, João Manuel CunhaTesting of urinary volatile organic metabolites (VOMs) is recognized as a useful medical approach since they are the end-products of metabolic processes and non-invasively sampling. Among the various techniques conventionally used for metabolic profiling, gas chromatography-quadrupole mass spectrometry (GC-qMS) is viewed as an effective approach for the testing of VOMs in urine due to its high sensitivity, peak resolution and reproducibility. Solid phase extraction (SPE), one of the sample preparation methods, has been proven to be a robust tool for the application in target VOMs concentration and separation from complex matrix. The aims of this study are to explore new nanomaterials (NMs), such as inorganic and carbon-based nanoparticles magnetic NPs (MNPs), combined with GC-qMS in order to isolate and pre-concentrate the target urinary VOMs, reported as possible cancer biomarkers. Concerning to the nanosorbent, the best efficiency of extraction is achieved with nanohydroxyapatite (NHA) and magnetic Fe3O4@SiO2-C18 NPs. Some experimental parameters such as, sorbent amount, adsorption and elution time, as nature of elution solvent, were investigated and compared. Under optimal conditions for nanohydroxyapatite (NHA) and magnetic Fe3O4@SiO2-C18 NPs, the obtained results revealed a good linearity (r2 ≥ 0.988) within the linear dynamic range, for all urinary volatile metabolites under study. The projected strategy showed low limits of detection (LODs), ranging from 9.7 to 69.5 ng/L, and low limits of quantification (LOQs) from 32.4 to 231.6 ng/L. The methodology also afforded suitable results in terms of matrix effect (62.8–96.1%) and accuracy, higher than 70 % for the majority of the investigated VOMs. The precision, expressed as intra- and inter-day repeatability, was lower than 3 and 13 %, respectively. Together, the NHA and Fe3O4@SiO2-C18 NPs-based sorbent extraction combined with GC-qMS in the current study provides a new, reliable and high throughput strategy for the determination of VOMs in human urine.