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As direct chemotherapy drugs are still unable to target the tumor, they frequently have systemic adverse effects and inadequate therapeutic efficacy if used to treat breast cancer. The excellent properties of nanogel make them good tools to provide more option for the targeted delivery of chemotherapeutic drugs. The objective of the present study was to build a unique nano-platform by combining a hydrogel and a cross-linked hydrophilic polymer (CA-Myr-NG), which has chitosan/alginate (CA) as the core to deliver the chemotherapeutic drug Myricetin (Myr), a naturally occurring flavonoid. The developed CA-Myr-NG was characterized using different approaches, including UV–vis, Zeta, DLS, FTIR, EDX, SEM and TEM analysis. The effects of CA-Myr-NG on MCF-7 cells were assessed using the cell viability, ROS generation, MMP levels and induced apoptosis. Apoptosis induction was measured using an Annexin V-florescien isothicyanate assay. Propidium iodide assay to evaluate the impact upon the cell cycle. Time dependent cell death was carried out by CA-Myr-NG. The maximum inhibitory effect was found to be 57 ± 2.7% when dosage of 6 µg/mL or higher were delivered after 24 h of treatment. Additionally, the CA-Myr-NG induced apoptosis in MCF-7 cells. Cell cycle arrest at G2/M phase and the presence of apoptotic MCF-7 cells were both found in 30.92% of the treated cells at a concentration of 6 µg/mL. The percentage of MCF-7 cells that entered the G2/M phase increased from 37.55% (untreated) to 45.44% (CA-Myr-NG). According to these findings, the CA-Myr-NG may be a promising candidate for targeted therapy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Iron nanoparticles are typically made from inorganic precursors, but for the first time, we synthesized-Fe2O3-NCs from goat blood (a bio-precursor) employing the RBC lysis method (a molecular level approach). After that, γ-Fe2O3-NPs were coated with PEG and combined with DOX to form nanocarriers (NC) for drug delivery. PEG–DOX–γ-Fe2O3-NCs were physicochemically investigated using A549 lung cancer cells as a model for in vitro and in vivo studies. The result revealed that PEG–DOX–γ-Fe2O3-NCs were 60–70 nm in size, confirming the presence of PEG and DOX in γ-Fe2O3-NCs. Cytotoxicity, morphological abnormalities, and intracellular iron recognition were observed in a dose-dependent manner in the cell line investigation. The presence of robust DOX signals in the nucleus shows that PEG–DOX–γ-Fe2O3-NCs were used for nuclear chemotherapy and cell uptake. In vivo, the rapid release of PEG–DOX–γ-Fe2O3-NCs was also observed. DOX suppresses carcinogenesis and has no toxicity in the healthy organs of tumor-bearing mice, according to investigated histological study. As a result, PEG–DOX–γ-Fe2O3-NCs synthesized from natural sources will be preferable to commercially available synthetic sources and can be employed as an anticancer agent. This nanocarrier will be developed in the future with various drug carrier systems for targeted nuclear treatment of cancer and other related diseases. [ABSTRACT FROM AUTHOR]

Amino acids play a crucial role in a variety of significant metabolic processes and their homeostasis is essential for cell growth and survival. Cysteine (Cys) furnishes imperative information about peculiar physiological functions and disease diagnosis. Cys detection in a biological solution has certain challenges. In this study, we present an appropriate and cost-effective colorimetric technique for the quantitative detection of Cys using label-free silver nanoparticles (Ag-NPs) as color indicators and Be2+ ions as cross-linking agents. The determination process needed to be based on the interaction of Ag-NPs with Cys molecules in the presence of beryllium ions, which induced a rapid pale yellow to red color conversion. The results indicate that this is a rapid and simple technique for quantitative analysis of Cys. In the linear range of 0.1–1000 μM, a detection limit of 50 nM was obtained. In addition, the technique was profitably applied to the detection of cysteine in human serum samples spiked with 250–5 μM and recoveries were in an acceptable range of 95.0–120.0%. This study might promote the implementation of label-free biomolecule detection in medical diagnostics and biochemistry. [ABSTRACT FROM AUTHOR]

• Increased number of identified CD44 peptied compared to the 12 h insolation digestion. • Enhanced proteolytic performance towards a complex of proteins with specific pI. • Desirable throughput consuming ∼6 min for proteolysis of serum samples. • Automated process in the sample pretreatment for online MS analysis. • Long term stability after two months storage, reusability with little memory effect. For molecular diagnostics in modern biomedical research, electrospray ionisation mass spectrometry (ESI-MS) based on proteome profiling is important. Now a days, sample preparation such as proteolysis and protein extraction remain incredibly challenging and inefficient. Recent sample-preparation methods based on micro tips show promising results toward the aim "a proteome in an hour". Proteolysis at the tip, is still infrequently observed and does not represent the processing of complex bio-samples. In this study, we outline a unique technique for detecting and extracting human serum CD44 biomarkers by ligand–protein interactions. This method employs macropores silica particles (MPSP) or (MOSF) modified with hyaluronic acid (HA). In order to assist in the profile of the human serum proteome, we limitations of immunoassays for rapid and multimodal proteolysis. For effective in situ proteolysis, in micropipette tips, MPSP were designed as nanoreactors with variable pore size and surface chemistry. In MS-based bottom-up proteome analysis, the device as-built demonstrated favourable sensitivity (LOD of 0.304 ± 0.007 ng/mL and LOQ of 0.973 ± 0.054 ng/mL), selectivity, durability (at −20 °C for 2 months), reuse (at least 10 times), and minimal memory impact. In addition, we examined into specific surface chemistries of nanoparticles for the absorption of proteins in serum and profiled the HA-binding serum proteome, setting a new preliminary benchmark for future databases. Our study not only helped establish a new platform for extracting/detection of CD44 and identifying the HA-binding proteome, but it also offered design recommendations for ligand affinity-based techniques for the antibody-free study of serum biomarkers with a view towards diagnostic applications. [ABSTRACT FROM AUTHOR]

Cisplatin is used to treat a variety of tumors, but dose-limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including breast. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule and characterized in terms of size, shape, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as received silica nanoparticles ranged from 20 to 90 nm. The results show that adverse effects on cell function, as evidenced by reduced metabolic activity measured by the MTT assay and increased membrane permeability observed using the live/dead stain, can be correlated with surface area of the silica. Cisplatin-functionalized silica nanoparticles with the highest surface area incited the greatest response, which was almost equivalent to that induced by free cisplatin. Moreover, if verified by further studies, would indicate that cisplatin was attached to silica nanoparticles might prove to be useful in site-specific drug delivery. [ABSTRACT FROM AUTHOR]

Silica nanoparticles as a nonviral vector forin vivogene therapy neither surface functionalized SiNp1 is neither “a cationic ion” nor a surface (encapsulation) nor SiNp2 (adsorption). p53 gene expression in the breast upon (i.v) administration. SiNp1 showed a 50- and 100-fold transfection activity, tumor growth inhibition, animal survival (80%), and high levels of p53 and Bax were detected in the sera of treated animals compared to SiNp2 or naked pCMV/p53, respectively. These results demonstrate for improvements in the both systems. This study suggests that nonviral vector systems will have important roles in achieving the impermanent gene transferin vivo. [ABSTRACT FROM AUTHOR]

In this study described a green approach for synthesizing silver nanoparticles (AgNPs) with corncob acting as a reducing and stabilizing agent to rapidly detect of L -Cysteine (Cys). To obtain an appropriate condition of synthesizing AgNPs variations in the reactant condition such as concentration, pH, and processing speed were altered. The synthesized AgNPs, that have sizes of 50–100 nm were capped by corncob extract (CCB), became virtually hexagonal and re-dispersed well in aqueous solution. AgNPs were explored for their possible structural characterization. Significantly, the CCB/AgNPs combination demonstrated very high sensitivity for Cys detection with a 30 nM limit of detection (LOD) and selective detection of Cys among 12 amino acids. Furthermore, the CCB/AgNPs combination was applied to detect Cys in human serum with an error rate of less than 5%. As a result of this work, a rapid approach for Cys detection employing green-synthesized AgNPs was developed. • For the synthesis of AgNPs, corn cob aqueous extract (CCB) was used as a reducing and stabilizing agent. • AgNPs with sizes of 50–100 nm had a polygonal form and dispersed well in aqueous solution. • AgNPs potential structural characterization was examined. • With a LOD of 30 nM, CCB/AgNPs demonstrated sensitive and selective cysteine detection. • CCB/AgNPs can detect cystine in human serum with excellent recovery in rats. [ABSTRACT FROM AUTHOR]

Objectives Mutations in the p53 tumor suppressor gene are one among the most common genetic abnormalities to be described in breast cancer. However, there are a few recant reports on non-viral vector-mediated p53 gene delivery in breast cancer. Methods A new formulation of luminescent silica nanoparticles (LSNs) for gene delivery was produced by the two-step method with slight modification. Key findings The pp53 plasmid constructs (p53-EGFP)/LSNs complexes were transfected into human breast cancer cell (MCF-7) and transfection efficiency was determined by FACS analysis. The gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis respectively. Further the growth inhibition through induced apoptosis with pp53-EGFP/LSNs complex were assessed by trypan blue exclusion assay and annexin V staining, respectively. Interestingly the in vivo biodistribution of plasmid DNA study revealed the occurrence was investigated by PCR and RT-PCR. The transfection efficiency of LSNs showed the highest transfection efficiency among the LSN formulation was higher than that of commercially available Lipofectin®. The LSNs-mediated transfection of the p53 gene resulted in efficient high level of wild-type p53 mRNA and protein expression levels in MCF-7 cells. Selected tissues were analyzed for any potential toxicity by histological analysis the efficient reestablishment of wild-type p53 function in breast cancer cells restored the p53 dependent apoptotic pathway. Conclusions Taken together, our results reveal that cationic LSN-mediated p53 gene delivery may have potential application as a non-viral vector-mediated breast cancer gene therapy due to its effective induction of apoptosis and tumor growth inhibition. [ABSTRACT FROM AUTHOR]

Objective: The objective of this article was to evaluate therapeutic outcomes of elderly patients with glioblastoma multiforme (GBM) treated by surgery followed by combined modality therapy and compare achievable outcomes to those of a younger age population. Methods and Materials: Seventy-eight adult patients with histologically confirmed grade IV astrocytoma were treated at King Hussein Cancer Center (Amman, Jordan) between September 2004 and December 2008. Records were retrospectively reviewed and included 55 males and 23 females between 19 and 78 years of age (median age 50 years). This case series included 20 patients aged 60 years or older. All patients underwent craniotomy followed radiotherapy and concurrent or sequential temozolomide. The follow-up ranged from 1 to 56 months (median 9.4 months). Results: The median survival for the whole cohort was 13.8 months. The median survival for patients less than 60 years was 14.3 months and for patients 60 years or older was 12.3 months ( P = 0.19). Among elderly patients, radical surgical resection ( P = 0.002), concurrent delivery of chemoradiation (0.041) and radiotherapy dose ≥5400 cGy ( P = 0.0001) conferred statistically significant improvements in overall survival. Conclusion: Management of GBM in elderly patients should include maximal surgical resection followed by radiotherapy and temozolomide whenever medically feasible. Outcomes comparable to those obtained in younger age groups can be expected. Our results indicate that concurrent chemoradiation is superior to sequential chemoradiation in these patients. [ABSTRACT FROM AUTHOR]