Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Ethanol reduces Ca2+ concentrations in arterial and venous smooth muscle

Summary The present results, using isolated rat aortic strips and portal vein segments, demonstrate that ethanol (170–430 mM) significantly inhibits calcium uptake in these 2 different types of vascular smooth muscle.Supported by NIH grant No. HL-18015 and NIMH grant No. MH-26236. Request for reprints should be addressed to B.M. Altura.     

Density gradient centrifugation of cells separated from multicellular tumor spheroids

Summary Cells from a murine fibrosarcoma (FSa) have been grown in vitro as multicell tumor spheroids (MTS). The growth rate of these MTS was determined. Follwing selected periods of growth, MTS were made into a single cell suspension and separated on linear density gradients of Renografin. While only 1 population of cells was separated from small spheroids (400 m diameter), at least 3 subpopulations of tumor cells were separated and isolated from large spheroids (800 m in diameter).This investigation was supported in part by grants numbered CA-18628 and CA-06294, awarded by the National Cancer Institute, DHEW.     

Octopus chromatophores accumulate nickel

Summary Microprobe analysis of the pigment granules in the superimposed chromatophore layers ofOctopus vulgaris reveal rising amounts of calcium, nickel and sulfur as the size and electron-density of the granules increases. The colours, associated with these increases, shift from yellow/orange to red and finally black.This work was prepared while A.P. was on study leave in Germany supported by the Deutscher Akademischer Austauschdienst.     

A rotating bottle culture method with continuous replacement of the gas phase

Summary A rotator culture method is described which provides a continuous flow of oxygenating gas to cultures in rotating bottles. The system maintains constant O₂ and CO₂ levels in the culture medium throughout the incubation period. It also provides a more stable pH than systems with sealed culture bottles.Acknowledgments. We would like to thank Mr B. Secker, Mr C. Hellon and Mr S. J. Ellis, of the Physiological Laboratory workshop, for constructing the rotator apparatus. We also thank the Medical Research Council, London, for financial support for the project.     

Ferns of Rajasthan-behaviour of chlorophyll and carotenoids in drought resistance

Summary The relationship of chlorophylls and carotenoids with drought resistance has been studied in some of the ferns found in Rajasthan, without heating as well as after heating the fronds at 60°C. The xerophytic species showed lesser degradation of chlorophyll and exhibited higher carotenoid contents.     

Inhibition of an early stage of erythropoiesis in cultures of young chick blastodisc cells byRicinus communis agglutinin 120

Summary An early pre-erythroid phase of erythropoiesis in cultures of dispersed cell suspensions prepared from primitive streak and head-fold chick blastodiscs was very sensitive to inhibition byRicinus communis agglutinin 120.This work was supported by grants from the Medical Research Council and National Research Council of Canada. We thank Mrs S. Dorey and N.N. McGrath for technical assistance. S.D.W. is an Associate of the Medical Research Council.