Fahmida Jabeen

Au-Nanomaterials as a Superior Choice for Near-Infrared Photothermal Therapy

Photothermal therapy (PPT) is a platform to fight cancer by using multiplexed interactive plasmonic nanomaterials as probes in combination with the excellent therapeutic performance of near-infrared (NIR) light. With recent rapid developments in optics and nanotechnology, plasmonic materials have potential in cancer diagnosis and treatment, but there are some concerns regarding their clinical use. The primary concerns include the design of plasmonic nanomaterials which are taken up by the tissues, perform their function and then clear out from the body. Gold nanoparticles (Au NPs) can be developed in different morphologies and functionalized to assist the photothermal therapy in a way that they have clinical value. This review outlines the diverse Au morphologies, their distinctive characteristics, concerns and limitations to provide an idea of the requirements in the field of NIR-based therapeutics.

Silica-lanthanum oxide: pioneer composite of rare-Earth metal oxide in selective phosphopeptides enrichment.

Relying on the successful journey of metal oxides in phosphoproteomics, lanthanum oxide is employed for the engineering of an affinity material for phosphopeptide enrichment. The lanthanum oxide is chemically modified on the surface of silica and characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FTIR). The obtained silica-lanthanum oxide composite is applied for the selective enrichment of phosphopeptides from tryptic digest of standard protein (α-casein, β-casein, and commercially available casein mixtures from bovine milk). The enriched entities are analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The mass spectroscopy (MS) results show that the silica-lanthanum oxide composite exhibits enhanced capability for phosphopeptide enrichment with sensitivity assessed to be 50 fmol. Sequence coverage of casein is interpreted showing successful recovery. As a real sample, a protein digest of nonfat milk is applied. Also, the ability of lanthanum in different formats is checked in the selective phosphopeptides enrichment. The composite holds promising future in economic ground as it also possesses the regenerative ability for repetitive use.

Versatile nanocomposites in phosphoproteomics: a review.

Protein phosphorylation is one of the most important post-translational modifications. Phosphorylated peptides are present in low abundance in blood serum but play a vital role in regulatory mechanisms and may serve as casual factors in diseases. The enrichment and analysis of phosphorylated peptides directly from human serum and mapping the phosphorylation sites is a challenging task. Versatile nanocomposites of different materials have been synthesized using simple but efficient methodologies for their enrichment. The nanocomposites include magnetic, coated, embedded as well as chemically derivatized materials. Different base materials such as polymers, carbon based and metal oxides are used. The comparison of nanocomposites with respective nanoparticles provides sufficient facts about their efficiency in terms of loading capacity and capture efficiency. The cost for preparing them is low and they hold great promise to be used as chromatographic materials for phosphopeptide enrichment. This review gives an overview of different nanocomposites in phosphoproteomics, discussing the improved efficiency than the individual counterparts and highlighting their significance in phosphopeptide enrichment.

High affinity phosphopeptides enrichment and desalting of biological materials on newly engineered poly(glycidyl propargyl ether/divinyl benzene).

The new synthetic polymers have a key role to play in the separation science. The derivatization of these polymers has made them an efficient class of substrate, having unique properties and the selectively tailored surface chemistries for target molecules. The deeper and detailed characterization of complex sample types has become feasible due to the enhanced selectivity and sensitivity offered by these polymer materials. In present work, a bifunctional monomer glycidyl propargyl ether (GPE) is thermally polymerized with divinylbenzene to form poly(GPE/DVB). Some of the physical and chemical properties are characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and Fourier transform infrared spectroscopy (FTIR). The synthesized polymer is further derivatized to IMAC (immobilized metal ion affinity chromatography) and is investigated by loading different metal ions (Fe(3+), Ti(4+), Zr(4+), and La(3+)). The trypsin-digested products of phosphoproteins, such as casein, nonfat milk, egg yolk, and human blood serum, are used to explore its phosphopeptide enrichment ability from complex samples followed by the off-line MALDI-MS analysis. Furthermore, polymeric reversed phase (RP) is created by octadecyl amine (ODA) to be employed in the desalting of complex mixtures and the results are compared with commercially available ZipTip C-18 and Aspire RP30 Desalting Tip. Serum profiling of healthy and diseased samples demonstrates the potential of this new polymer to impart in the disease diagnosis. Ovarian carcinoma serum samples are used for the detection of phosphopeptides based biomarkers.

Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids.

Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe(3+) and La(3+) ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program (www.matrixscience.com) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification.

Newly Fabricated Magnetic Lanthanide Oxides Core–Shell Nanoparticles in Phosphoproteomics

Metal oxides show high selectivity and sensitivity toward mass spectrometry based enrichment strategies. Phosphopeptides/phosphoproteins enrichment from biological samples is cumbersome because of their low abundance. Phosphopeptides are of interest in enzymes and phosphorylation pathways which lead to the clinical links of a disease. Magnetic core-shell lanthanide oxide nanoparticles (Fe3O4@SiO2-La2O3 and Fe3O4@SiO2-Sm2O3) are fabricated, characterized by SEM, FTIR, and EDX and employed in the enrichment of phosphopeptides. The nanoparticles enrich phosphopeptides from casein variants, nonfat milk, egg yolk, human serum and HeLa cell extract. The materials and enrichment protocols are designed in a way that there are almost no nonspecific bindings. The selectivity is achieved up to 1:8500 using β-casein/BSA mixture and sensitivity down to 1 atto-mole. Batch-to-batch reproducibility is high with the reuse of core-shell nanoparticles up to four cycles. The enrichment followed by MALDI-MS analyses is carried out for the identification of phosphopeptides from serum digest and HeLa cell extract. Characteristic phosphopeptides of phosphoproteins are identified from human serum after the enrichment, which have the diagnostic potential toward prostate cancer. Thus, the lanthanide based magnetic core-shell materials offer a highly selective and sensitive workflow in phosphoproteomics.

Newly developed poly(allyl glycidyl ether/divinyl benzene) polymer for phosphopeptides enrichment and desalting of biofluids.

The polymeric materials have contributed significantly in the area of bioanalytical science. The functionalization of polymeric backbone after its development brings unique selectivity towards the target biomolecules. In present work, the functionalities of choice have been introduced through the ring-opening of allyl glycidyl ether. The utility of polymer is widened through derivatizations to immobilized metal ion affinity chromatographic (IMAC) material for the phosphopeptides enrichment and Reversed Phase (C-18) for the desalting prior to MALDI-MS analysis. The polymer-IMAC in addition to Fe(3+) is also immobilized with lanthanide ions like La(3+), Eu(3+), and Er(3+). The amount of Fe(3+) immobilized is determined as 0.7928 mg/g. Spherical morphology with narrow particle size dispersion is revealed by scanning electron microscopy (SEM). The surface area, pore volume and size distribution is determined by nitrogen adsorption porosimetery. The elemental composition and purity level is confirmed by energy dispersive X-ray spectroscopy (EDX) data. The derivatization to IMAC and RP is evaluated by Fourier transform infrared (FT-IR) spectroscopy. The polymer enables the efficient phosphopeptide enrichment to equal degree from casein variants, non-fat milk, egg yolk, human serum, and HeLa cell extract. The identification of phosphorylation sites can lead to the phosphorylation pathways to understand the post-translational modifications. The identification with their sequence coverage is made using Mascot and Phosphosite Plus. It is sensitive to enrich the phosphopeptides down to 2 femtomoles with very high selectivity of 1:2000 with BSA background. These attributes are linked to the higher surface area (173.1554 m(2)/g) of the designed polymer. The non-specific bindings, particularly the Fe(3+) linked acidic residues are also avoided. Four characteristic phosphopeptides (fibrinopeptide A and their hydrolytic products) from fibrinogen α-chain are identified from the human serum after the enrichment, which have link to the hepatocellular carcinoma (HCC). The proportions of fibrinogen and their phosphorylation products enriched by poly(AGE/DVB)-IMAC open new horizons in the biomarker discovery.

Enhanced enrichment performance of nickel oxide nanoparticles via fabrication of a nanocomposite with a graphene template

Metal oxide based nanocomposites are applied in phosphoproteomics for enrichment through the surface hydroxyl groups of metal oxides, though the role of the metal is rarely described. Using graphene as a template after modification with nickel oxide, a nanocomposite with an increased surface area is fabricated and applied to phosphopeptides. Characterisation shows a narrow size distribution of 15–20 nm, BET surface area of 179.70 m2 g−1 and a pore volume of 0.44 cm3 g−1. The graphene possesses well distributed NiO nanoparticles showing selectivity up to 1000 folds of complexity with a sensitivity as low as 1 femtomole. The G–NiO nanocomposite shows a higher selectivity towards phosphopeptides compared to TiO2, ZrO2 and NiO nanoparticles. The enrichment with the G–NiO nanocomposite is tested for biological samples like egg yolk, non-fat milk and human serum. Phosphopeptides having phosphorylations of up to 6 phosphate groups, derived from phosvitin and lipovitellin, are enriched in the egg yolk digest. Phosphopeptides characteristic of casein variants are enriched in the non-fat milk digest with a recovery of αS1 21.9%, αS2 30% and β-casein 20%. Phosphorylated proteins are identified in human serum through the enrichment of phosphopeptides.

In-Tip Lanthanum Oxide Monolith for the Enrichment of Phosphorylated Biomolecules

Polymeric monoliths fabricated in tips with embedded materials of choice are important in separation science. Polymeric backbone however interferes in the enrichment and thus affects efficiency. This work focuses on the in-tip fabrication of lanthanum oxide porous monolith and its application in the enrichment of phosphorylated peptides and lipids. Polycondensation reaction uses an aqueous solution of LaCl3·7H2O with N-methyl formamide as porogen and propylene oxide as initiator. The aging time of monolith and temperature condition for the reaction are optimized to attain porous monolithic tip. A comparison of (i) solid phase batch extraction using La2O3, (ii) La2O3 embedded in poly(glycidyl methacrylate (GMA)/divinylbenzene (DVB)) tip, and (iii) pure La2O3 monolithic tip shows improved enrichment efficiency in the case of pure La2O3 monolithic tip. The monolithic tip achieves selectivity of 1:4500 as compared to solid phase extraction (SPE)(1:3500) and limit of detection down to 0.25 fmol. The in-tip La2O3 monolith strategy has better batch to batch reproducibility, reduced time of enrichment, and ease of operation in comparison to solid phase batch extraction. The developed strategy enriches phospho- content from biological samples like phosvitin and lipovitellin from egg yolk and phospholipids/phosphopeptides from human serum. The enriched phospho- moieties are analyzed by matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) except the phospholipids where laser desorption ionization (LDI)-MS is employed.

New cellulose–silica composite IMAC/C18 for the selective enrichment of phosphorylated molecules and the improved recovery of hydrophilic species

Cellulose and silica are the traditional quality sorbents with a range of reported applications, particularly for hydrophilic biomolecules. With this in mind, cellulose and silica were brought into a composite form to bring their individual benefits on to a single platform. Cellulose and silica were chosen in order to obtain a completely hydrophilic composite, which was then derivatized for the selective enrichment of phosphopeptides and as a desalting material prior to mass spectrometric analysis. The composite was characterized by FT-IR, EDX and SEM. As a material for immobilized metal ion affinity chromatography (IMAC), the cellulose–silica composite enriches phosphopeptides from a complex mixture in which β-casein is spiked in de-phosphorylated HeLa cell extract. The inherent hydrophilic nature of the composite gives a higher selectivity of up to 2000 times the complexity level and sensitivity down to 1 femtomole for phosphopeptides. As well as the immobilized metal ions on the IMAC composite, the roles of the base materials in the composite, i.e. cellulose and silica were also tested in the enrichment which helped thereof in optimizing the best sample preparation protocol. With the introduction of successive elution conditions, phospholipids and phosphopeptides were enriched and identified from egg yolk digest using a single batch extraction method. The phosphopeptides were analyzed with MALDI-MS, whereas the low molecular weight phospholipids were analysed using newly designed gold nanoparticles and carbon based materials through LDI-MS. Phosphopeptides were also enriched from complex serum digest and discussed with relevance to prostate cancer. As a reverse-phase (RP) material, it provides a combination of the hydrophilic composite and the hydrophobic C18 chain. Efficient desalting of higher salt concentrations, improved recovery of hydrophilic peptides and high sequence coverage in comparison to commercial materials makes cellulose–silica C18 a better desalting tool with in-house economical synthesis.