Nano-biotechnology in tumour and cancerous disease: A perspective review

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.     

Extracellular material from Leuconostoc mesenteroides subsp. dextranicum mediates the aggregation of lactococcal cells: implications for the isolation of single strains

Cultures of Lactococcus lactis subsp. cremoris , originally derived from mixed cheese starter cultures, were assessed as pure following single colony selection and subculturing, yet nevertheless gave rise, under stress conditions, to an isolate with the ability to ferment citrate. The isolate was characterized with respect to its citrate enzymology and lactose fermentation and was identified as Leuconostoc mesenteroides subsp. dextranicum and assigned the strain number 663. The extracellular material (ECM) from Leuc. mesenteroides subsp. dextranicum 663 was characterized and found to contain carbohydrate, protein and phosphate (30.9, 50.7 and 18.4%, by weight, respectively). Glucose was the most prominent sugar (39% by weight of total carbohydrate) with mannose, galactose and rhamnose being the other major monosaccharides. The ECM protein resolved into a large number of bands on SDS-polyacrylamide gel electrophoresis, the most prominent having molecular masses of 40 and 49 kDa. The ECM from Leuc. mesenteroides subsp. dextranicum 663 caused aggregation of suspensions of lactococcal cells and may facilitate intergeneric interactions and/or co-culture during cheese starter strain isolation.     

Denitrification of nitrate to nitrogen gas by washed cells ofRhizobium japonicum and by bacteroids fromGlycine max

Nitrate, nitrite and nitrous oxide were denitrified to N₂ gas by washed cells ofRhizobium japonicum CC706 as well as by bacteroids prepared from root nodules ofGlycine max (L.) Merr. (CV. Clark 63). Radiolabelled N₂ was produced from either K¹⁵NO₃ or Na¹⁵NO₂ by washed cells ofRh. japonicum CC705 grown with either nitrate only (5 mM) or nitrate (5 mM) plus glutamate (10 mM). Nitrogen gas was also produced from N₂O. Similar results were obtained with bacteroids ofG. max. The stoichiometry for the utilization of¹⁵NO ₃ ^- or¹⁵NO ₂ ^- and the produciton of¹⁵N₂ was 2:1 and for N₂O utilization and N₂ production it was 1:1. Some of the¹⁵N₂ gas produced by denitrification of¹⁵NO ₃ ^- in bacteroids was recycled via nitrogenase into cell nitrogen.     

Effects of growth conditions on the activities of superoxide dismutase and NADH-oxidase/NADH-peroxidase inStreptococcus lactis

An increase in the superoxide dismutase (SOD) activity inStreptococcus lactis was observed when the cells were grown at increased oxygen partial pressures or exposed to hyperbaric oxygen tensions. The NADH-oxidase/NADH-peroxidase activities inS. lactis increased in galactose-grown cells when cultivated in air compared with N₂/CO₂. This effect did not occur when glucose was the carbon source; however, an increase in the activities of these enzymes was observed in oxygen atmosphere. The correlation between SOD, NADH-oxidase/NADH-peroxidase, and the metabolic pathways involved is discussed. The effect of manganese on the SOD activity is also considered.     

Leaf architecture of some acanthaceae

Leaf architectural pattern has been studied in 27 genera and 35 species of the Acanthaceae. The major venation pattern conforms to pinnate camptodromous with eucamptodromous or festooned brochidodromous secondaries, pinnate craspedodromous inAcanthus ilicifolius and acrodromous inLepidagathis trinervis. Intersecondary veins are common. The marginal ultimate venation is looped. The areoles are variable in size. The vein endings are usually simple, linear or cuved or divide once or twice dichotomously. Isolated vein endings, tracheids, isolated free vein endings and extension cells are observed. Transfusion tracheids are seen inDicliptera verticillata. Miniature vessel elements with simple perforation plates are noticed lying free in the areole or at the end of tracheids inSeriocalyx scaber andThunbergia grandiflora.Elytraria acaulis, Nelsonia canescens andStaurogynae zeylanica exhibit venation pattern shown by majority of the taxa studied, of the Acanthaceae.     

Abnormalities in the fine structure of the spermatids of rats injected with cadmium

The degenerative changes in the spermatids as measured by changes in fine structure abnormalities increased with time following injection of Cd²⁺ into rat testis. The spermatids in the twelve hours group appear as peculiarly club shaped and elongated structures with one or two small but perceptible vacuoles. The subacrosomal area and the space between the nucleus and the middle piece are seen abnormally dilated. In the 30 day group, the central filaments are the most susceptible unit of 9+2 axoneme complex. The plasma membrane, the cytoplasmic matrix, the mitochondria of the middle piece and the fibrous sheath appear shrunken, discontinuous and degenerative.     

Purification and properties of a nuclear protein kinase from rat mammary gland

A nuclear protein kinase that shows a high degree of substrate specificity for the phosphorylation of the acidic proteins casein, phosvitin and non-histone chromatin proteins, rather than the basic proteins histones and protamine, was partially purified from lactatingrat mammary gland. The enzyme is associated with the acidic protein fraction of chromatin. Nuclear kinase requires Co²⁺ for activity, and other bivalent cations such as Mg²⁺ and Mn²⁺ can substitute partially for Co²⁺. The kinase is further activates (2–3-fold) by various salts, their concentration for maximum stimulation being: NaCl, 150mm; KCl, 200mm; sodium acetate, 300mm. The sedimentation coefficient of the nuclear kinase is 8.9S and its mol.wt. is approx. 300000 by gel-exclusion chromatography. The enzyme is not activated by cyclic AMP or cyclic GMP and is inhibited neither by the regulatory subunit of mammary cyclic AMP-dependent protein kinase nor by the heat-stable protein kinase inhibitor from ox heart. Analysis of ³²P-labelled protein products reveals that the kinase transfers the terminal phosphate of ATP to serine and threonine residues of proteins. The enzyme, however, has specificity for the phosphorylation of threonine in casein and serine in phosvitin. Molecular size and enzymic characteristics of the nuclear protein kinase are clearly different from those of the cytosol enzyme previously characterized.     

Membrane-fusions and cytoplasmic bridges in the cells of the developing cerebellum

Summary In the developing cerebellum of the neonate rats membranefusions and cytoplasmic bridges between cells were observed. These membrane-fusions were characterized by the presence of loops of membrane and cytoplasmic bridges between the two limits of the membrane-fusions. They were found between Purkinje cells, Purkinje cells and the migratory cells, mitotically potent cells of the external granular layer, and differentiating granule cells of the internal granular layer. The membrane-fusions were found to be a transient developmental phenomenon. Issues pertaining to the universality of membrane-fusions, their significance in the induction for cell differentiation, and the problem of fixation artifacts are discussed.This research was supported by N.I.H. Research Grants No. NS-08817 and CA-14650. Assistance of Mrs. Kunda Das in various aspects of electron microscopy is gratefully acknowledged     

Prolactin secreting cells in the hypophysis of the brown spiny mouseMus platythrix (Bennett)

Prolactin secreting cells are identified in thepars distalis of Mus platythrix by conventional methods of light and electron microscopy. Two types of prolactin secreting cells are recognised. These types are estrone-sensitive, mammotrophic type I, and luteotrophic type II, respectively. Histochemical analysis revealed that the cells are rich in RNA, basic proteins, alkaline phosphatase and are resistant to extraction with 0·5% trichloroacetic acid. Quantitative data showed that the prolactin secreting cells increase during pregnancy, lactation and estrone treatment. Estrone at low dose levels caused immense hyperplasia whereas at higher levels there was no corresponding increase in the percentage of type I cells. Ultrastructurally, prolactin secreting cells are characterised by the presence of stacked endoplasmic reticulum, oval or irregular secretory granules. The Golgi apparatus is seen rich in vacuolar system.     

Hexokinase receptors: Preferential enzyme binding in normal cells to nonmitochondrial sites and in transformed cells to mitochondrial sites

Hexokinase plays an important role in normal glucose-utilizing tissues like brain and kidney, and an even more important role in highly malignant cancer cells where it is markedly overexpressed. In both cell types, normal and transformed, a significant portion of the total hexokinase activity is bound to particulate material that sediments upon differential centrifugation with the crude mitochondrial fraction. In the case of brain, particulate binding may constitute most of the total hexokinase activity of the cell, and in highly malignant tumor cells as much as 80 percent of the total. When a variety of techniques are rigorously applied to better define the particulate location of hexokinase within the crude mitochondrial fraction, a striking difference is observed between the distribution of hexokinase in normal and transformed cells. Significantly, particulate hexokinase found in rat brain, kidney, or liver consistently distributes with nonmitochondrial membrane markers whereas the particulate hexokinase of highly glycolytic hepatoma cells distributes with outer mitochondrial membrane markers. These studies indicate that within normal tissues hexokinase binds preferentially to non-mitochondrial receptor sites but upon transformation of such cells to yield poorly differentiated, highly malignant tumors, the overexpressed enzyme binds preferentially to outer mitochondrial membrane receptors. These studies, taken together with the well-known observation that, once solubilized, the particulate hexokinase from a normal tissue can bind to isolated mitochondria, are consistent with the presence in normal tissues of at least two different types of particulate receptors for hexokinase with different subcellular locations. A model which explains this unique transformation-dependent shift in the intracellular location of hexokinase is proposed.