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Ambikesh Soni Manohar Prasad Bhandari Gagan Kant Tripathi Priyavand Bundela Pradeep Kumar Khiriya Purnima Swarup Khare Manoj Kumar Kashyap Abhijit Dey Balachandar Vellingiri Suresh Sundaramurthy Arisutha Suresh José M. Pérez de la Lastra 《Journal of cellular and molecular medicine》2023,27(6):737-762
In recent years, drug manufacturers and researchers have begun to consider the nanobiotechnology approach to improve the drug delivery system for tumour and cancer diseases. In this article, we review current strategies to improve tumour and cancer drug delivery, which mainly focuses on sustaining biocompatibility, biodistribution, and active targeting. The conventional therapy using cornerstone drugs such as fludarabine, cisplatin etoposide, and paclitaxel has its own challenges especially not being able to discriminate between tumour versus normal cells which eventually led to toxicity and side effects in the patients. In contrast to the conventional approach, nanoparticle-based drug delivery provides target-specific delivery and controlled release of the drug, which provides a better therapeutic window for treatment options by focusing on the eradication of diseased cells via active targeting and sparing normal cells via passive targeting. Additionally, treatment of tumours associated with the brain is hampered by the impermeability of the blood–brain barriers to the drugs, which eventually led to poor survival in the patients. Nanoparticle-based therapy offers superior delivery of drugs to the target by breaching the blood–brain barriers. Herein, we provide an overview of the properties of nanoparticles that are crucial for nanotechnology applications. We address the potential future applications of nanobiotechnology targeting specific or desired areas. In particular, the use of nanomaterials, biostructures, and drug delivery methods for the targeted treatment of tumours and cancer are explored. 相似文献
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The kinetic mechanism for the interaction of D-cycloserine with serine hydroxymethyltransferase (EC 2.1.2.1) from sheep liver was established by measuring changes in the activity, absorbance, and circular dichoism (CD) of the enzyme. The irreversible inhibition of the enzyme was characterized by three detectable steps: an initial rapid step followed by two successive steps with rate constants of 5.4 X 10(-3) s-1 and 1.4 X 10(-4) s-1. The first step was distinguished by a rapid disappearance of the enzyme absorbance peak at 425 nm, a decrease in the enzyme activity to 25% of the uninhibited velocity, and a lowering of the CD intensity at 432 nm to about 65% of the original value. The second step of the interaction was accompanied by a complete loss of enzyme activity and a marginal increase in the CD intensity at 432 nm. The final step resulted in the complete loss of the enzyme absorbance at 425 nm and of the CD band at 432 nm. The products of the reaction were identified as (a) apoenzyme by absorbance measurements, CD spectra, and reconstitution with pyridoxal 5'-phosphate and (b) a pyridoxal 5'-phosphate-D-cycloserine Schiff's base complex identified by its fluorescence and absorbance spectra. The Schiff base complex was expelled from the enzyme active site in the final step of the reaction. The proposed mechanism, which is different from those operative in other pyridoxal phosphate dependent enzymes, probably accounts for the selective inhibition of serine hydroxymethyltransferase by the drug in vivo. 相似文献
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Identification of active-site residues of sheep liver serine hydroxymethyltransferase. 总被引:1,自引:1,他引:0
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Chemical modification of amino acid residues with phenylglyoxal, N-ethylmaleimide and diethyl pyrocarbonate indicated that at least one residue each of arginine, cysteine and histidine were essential for the activity of sheep liver serine hydroxymethyltransferase. The second-order rate constants for inactivation were calculated to be 0.016 mM-1 X min-1 for phenylglyoxal, 0.52 mM-1 X min-1 for N-ethylmaleimide and 0.06 mM-1 X min-1 for diethyl pyrocarbonate. Different rates of modification of these residues in the presence and in the absence of substrates and the cofactor pyridoxal 5'-phosphate as well as the spectra of the modified protein suggested that these residues might occur at the active site of the enzyme. 相似文献
5.
Temporal changes in the physical properties of healing fractures in rabbits were studied. The mechanical environment at the fracture site was measured and monitored during healing. Animals were sacrificed after 3 to 8 weeks. The results of healing were quantified by whole bone dynamic torsional strength tests. Torque-angle curves were recorded by computer. At maximum torque four parameters were calculated: torque, angle, energy absorbed and stiffness. Torque and stiffness increased while energy remained constant and angle decreased with time. However, values calculated by a constant deformation criteria showed the three strength parameters to increase with time. The rate of increase was highest for stiffness followed by torque and energy. 相似文献
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Crotaverrine and O-acetylcrotaverrine, isolated from the seeds of C. verrucosa Linn., have been shown by spectroscopy and chemical evidence to be the macrocyclic diesters of otonecine and diastereoisomeric integerrinecic acid. Hitherto, diastereoisomeric integerrinecic acid esters were not known to occur in nature. 相似文献
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To accurately predict rewards associated with states or actions, the variability of observations has to be taken into account. In particular, when the observations are noisy, the individual rewards should have less influence on tracking of average reward, and the estimate of the mean reward should be updated to a smaller extent after each observation. However, it is not known how the magnitude of the observation noise might be tracked and used to control prediction updates in the brain reward system. Here, we introduce a new model that uses simple, tractable learning rules that track the mean and standard deviation of reward, and leverages prediction errors scaled by uncertainty as the central feedback signal. We show that the new model has an advantage over conventional reinforcement learning models in a value tracking task, and approaches a theoretic limit of performance provided by the Kalman filter. Further, we propose a possible biological implementation of the model in the basal ganglia circuit. In the proposed network, dopaminergic neurons encode reward prediction errors scaled by standard deviation of rewards. We show that such scaling may arise if the striatal neurons learn the standard deviation of rewards and modulate the activity of dopaminergic neurons. The model is consistent with experimental findings concerning dopamine prediction error scaling relative to reward magnitude, and with many features of striatal plasticity. Our results span across the levels of implementation, algorithm, and computation, and might have important implications for understanding the dopaminergic prediction error signal and its relation to adaptive and effective learning. 相似文献
9.
Jaing C Gardner S McLoughlin K Mulakken N Alegria-Hartman M Banda P Williams P Gu P Wagner M Manohar C Slezak T 《PloS one》2008,3(5):e2163
Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples. 相似文献
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