Designing DNA cage-based immuno-fluorescence strategy for rapid diagnosis of clinical cervical cancer tissues

Exploiting a tissue diagnosis method to abstain the involuted operating and consume valuable reagents while realizing high-speed and inexpensive pathological grading technology to supply a better scheme for cancer therapy is a significant method of cancers detection. A promising immuno-fluorescence strategy was rationally designed and synthesized by loading ruthenium complex into cervical cancer-targeted DNA-cage, which was well used to realize high-speed and inexpensive diagnosis of clinical ce...     

Scoring functions: A view from the bench

Computational approaches to drug design are presently hindered by the complexity of the physical chemistry which underlies weak, non- covalent interactions between protein targets and small molecule ligands. Although a number of programs are now available for the design of novel potential ligands, it remains a key problem to rank these rapidly and reliably by estimated binding affinity. Such a step is necessary to select only the most promising candidates for synthesis and experimental characterisation. To calculate ligand affinity quickly and reliably is an extremely difficult problem, but it may well prove possible to estimate sufficiently accurately given an appropriate set of parameters to score individual protein–ligand interactions. Improvements in the situation will require a wider set of thermodynamically characterised systems than is currently available.     

Current trends in separation of plasmid DNA vaccines: A review

Plasmid DNA (pDNA)-based vaccines offer more rapid avenues for development and production if compared to those of conventional virus-based vaccines. They do not rely on time- or labour-intensive cell culture processes and allow greater flexibility in shipping and storage. Stimulating antibodies and cell-mediated components of the immune system are considered as some of the major advantages associated with the use of pDNA vaccines. This review summarizes the current trends in the purification of pDNA vaccines for practical and analytical applications. Special attention is paid to chromatographic techniques aimed at reducing the steps of final purification, post primary isolation and intermediate recovery, in order to reduce the number of steps necessary to reach a purified end product from the crude plasmid.     

Recent progress of vaccines administration via microneedles for cancer immunotherapy

Therapeutic cancer vaccines have undergone a resurgence in the past decade. Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis, percutaneous vaccination is considered to be an ideal treatment route. For convenient administration, the recent development of microneedles(MNs) provides a safe, painless, and low-cost transdermal delivery strategy, which could bypass the first-pass metabolism of vaccines for enhanced stability and bioavailabilit...     

Nanostructured electrochemical DNA biosensors for detection of the effect of berberine on DNA from cancer cells

Multi walled carbon nanotubes (MWNT) in dimethylformamide (DMF) or aqueous sodium dodecyl sulfate (SDS) solution, colloidal gold nanoparticles (GNP) in phosphate buffer solution (PBS), and a GNP–MWNT mixture in aqueous SDS solution have been investigated for chemical modification of a screen-printed carbon electrode used as the signal transducer of a dsDNA-based biosensor. Differential pulse voltammetry of the DNA redox marker and the guanine moiety anodic oxidation and cyclic voltammetry with K₃[Fe(CN)₆] as indicator revealed substantial enhancement of the response of the biosensor, particularly when MWNT in SDS solution was used. The biosensor was used in testing of berberine, an isoquinoline plant alkaloid with significant antimicrobial and anticancer activity. Berberine had a very strong, concentration-dependent, effect on the structural stability of DNA from the human cancer cells (U937 cells) whereas non-cancer cells were changed only when berberine concentrations were relatively high 75 and 50 μg mL⁻¹. Figure Schematic illustration of preparation of the nanostructured films: (a) layer-to-layer coverage (DNA/nanomaterial/SPE); (b) mixed coverage (DNA-nanomaterial/SPE)     

Impedimetric biosensor for early detection of cervical cancer

An impedimetric biosensor based on PEGylated arginine functionalized magnetic nanoparticles for early detection of cervical cancer is reported. The cervical cancer cells could be selectively and sensitively detected down to 10 cells mL(-1) on the modified electrode, which is promising for advancement in clinical diagnosis and monitoring of tumors.     

Synthesis of cancer peptide antigen-lipid A analog conjugates for synthetic vaccines.

Conjugates 6 and 7 of cancer peptide antigen with N-tetradecanoyl L-serine-beta-alanine-containing D-glucosamine derivative structurally related to lipid A as an immunoadjuvant were synthesized for the development of totally synthetic vaccines against cancers. The mitogenic activities of compounds 6 and 7 were stronger than that of lipid A analog 3.     

Polarons in DNA: transition from guanine to adenine transport

Experiments on hole transport in DNA have been interpreted as showing that a hole introduced onto a guanine (G) followed by a series of adenines (As) in a DNA duplex travels through the first three As by tunneling and then, with thermal energy, makes the transition onto the bridge of As. It has been widely believed that, once on the bridge, the hole is localized on a single A and proceeds by hopping between As. In the experiments, the holes on the A bridge diffuse, with little attenuation, until trapped by a GGG sequence. Recently, it has been discovered by Bixon and Jortner that the model of tunneling followed by hopping between As cannot account for the very weak dependence on bridge size of the relative chemical yields and the ratios of the rates for the two processes. In earlier calculations, we have shown that interaction with water results in the hole becoming a polaron spread over approximately four As. According to these calculations, the energy of the hole on the polaron is decreased so much that it is lower than that of the hole on G and even that of GGG. Estimates of energy fluctuations, due to fluctuations in the environment and conformational changes of the DNA, find them to be large enough so that GGG, and even G, can still act as hole traps, but trapping on the former is still very much more likely because of its lower energy.     

High-dimensional zinc porphyrin nanoframeworks as efficient radiosensitizers for cervical cancer

Radiotherapy is widely used clinically, but the toxic and side effects of nonselective killing of high-energy radiation limit its application. Finding biocompatible materials to assemble radiotherapy sensitizers and studying their sensitization patterns are of great significance for the clinical application. Here, biocompatible zinc porphyrin was chosen as sub-unit to construct various dimensional coordination frameworks. By employing top-down approach, suitable nanoframeworks with various dimensional zinc porphyrin were synthesized as radiosensitizers. The experimental data showed that high-dimensional zinc porphyrin nanoframeworks exhibit higher X-ray response performance.     

Direct energy transfer from conjugated polymer to DNA intercalated dye: label-free fluorescent DNA detection

The development of methods for DNA detection is of importance in disease diagnosis, gene-targeted drug discovery and molecular biology field. In this paper, we synthesize a new cationic water-soluble CP containing fluorene moiety and flexible ethylenic moiety in the backbone (PFV) for label-free DNA detection. The conformational freedom of PFV provides stronger interactions with double-stranded DNA (dsDNA) and optimizes the orientation of transition moments between PFV and ethidium bromide (EB) intercalated in dsDNA. The efficient FRET from PFV (donor) to EB (acceptor) intercalated in dsDNA is observed and the emission of EB is amplified by the good light-harvesting ability of conjugated polymers. The interactions between PFV and DNA can also be probed by measuring the FRET ratio between PFV and EB intercalated in DNA. In comparison to other DNA detection assays based on FRET and conjugated polymers, synthesis of dye-labeled DNA probe is avoided in our method, which significantly reduces the cost and the synthetic complexity. The PFV/dsDNA/EB system provides promising applications on DNA detection with a simply, fast and label-free manner.     

Thermosensitive mucoadhesive gel formulation loaded with 5-Fu: cyclodextrin complex for HPV-induced cervical cancer

Human Papilloma Virus (HPV) infections are the major cause of cervical cancers. To achieve a better therapeutic efficacy and patient compliance in the treatment for HPV-induced cervical cancers, anticancer agent 5-fluorouracil has been formulated in a vaginal gel using the thermosensitive polymer Pluronic^® F127 together with alternative mucoadhesive polymers e.g., hyaluronic acid, Carbopol 934 and hydroxypropylmethylcellulose. To increase its aqueous solubility and to achieve the complete release of 5-FU from the gel, the drug was incorporated as its inclusion complex with 1:1 molar ratio with either β-cyclodextrin or hydroxypropyl-β-cyclodextrin. Following the characterization of drug:CD complexes, thermosensitive gel formulations containing different mucoadhesive polymers and the drug in free or complexed form were characterized in vitro by determining the gelation temperature and the rheological behavior of different formulations along with the in vitro release profiles of these formulations in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin accelerated the release of 5-FU with the exception of formulation containing Carbopol 934 as mucoadhesive polymer. As far as rheological properties are concerned, favorable thermosensitive in situ gelling properties were obtained with formulations containing HPMC as mucoadhesive polymer. Complete release of 5-FU from gels were obtained with both complexes of β-CD and HP-β-CD and cytotoxicity studies against HeLa human cervical carcinoma cells demonstrated that 1% 5-FU:CD complexes were equally effective as 1% free 5-FU indicating better therapeutic efficacy with lower dose.     

Radiation damage to DNA: electron scattering from the backbone subunits

In the context of damage to DNA by low energy electrons, we carry out calculations of electron scattering from tetrahydrofuran and phosphoric acid, models of the subunits in the DNA backbone, as a first step in simulating the electron capture process that occurs in the cell. In the case of tetrahydrofuran, we also compare with previous theoretical and experimental data. A comparison of the shape of the resonant structures to virtual orbitals is also performed to gain insight into the systematic connections with electron scattering from similar molecules and dissociative electron attachment experiments.     

Sensitization of cancer cells to DNA damaging agents by imidazolines

Apoptosis, or programmed cell death, is a cellular mechanism used to regulate cell number and eliminate damaged or mutated cells. Concomitant with the initiation of the apoptotic cell signal, chemotherapeutic agents also induce anti-apoptotic factors, such as NF-kappaB, which compromise the overall efficacy of chemotherapeutic anticancer treatment. Here we describe an adjuvant therapy in which a small molecule is used to sensitize cancer cells toward apoptosis induced by chemotherapeutics. Our results indicate that the imidazoline 1d modulates the pro-survival NF-kappaB pathway and selectively sensitizes cancer cells toward DNA damaging agents, thus enhancing the overall efficacy of the treatment. Pretreatment of cancer cells with the noncytotoxic imidazoline 1d (10 nM) resulted in a significant increase in apoptosis and anticancer efficacy of the clinically significant DNA damaging agents camptothecin and cisplatin. Noncancerous cells remained unaffected during this regimen.     

DNA aptamer folding on gold nanoparticles: from colloid chemistry to biosensors

We have investigated the effect of the folding of DNA aptamers on the colloidal stability of gold nanoparticles (AuNPs) to which an aptamer is tethered. On the basis of the studies of two different aptamers (adenosine aptamer and K+ aptamer), we discovered a unique colloidal stabilization effect associated with aptamer folding: AuNPs to which folded aptamer structures are attached are more stable toward salt-induced aggregation than those tethered to unfolded aptamers. This colloidal stabilization effect is more significant when a DNA spacer was incorporated between AuNP and the aptamer or when lower aptamer surface graft densities were used. The conformation that aptamers adopt on the surface appears to be a key factor that determines the relative stability of different AuNPs. Dynamic light scattering experiments revealed that the sizes of AuNPs modified with folded aptamers were larger than those of AuNPs modified with unfolded (but largely collapsed) aptamers in salt solution. From both the electrostatic and steric stabilization points of view, the folded aptamers that are more extended from the surface have a higher stabilization effect on AuNP than the unfolded aptamers. On the basis of this unique phenomenon, colorimetric biosensors have been developed for the detection of adenosine, K+, adenosine deaminase, and its inhibitors. Moreover, distinct AuNP aggregation and redispersion stages can be readily operated by controlling aptamer folding and unfolding states with the addition of adenosine and adenosine deaminase.