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Advanced Drug Delivery Reviews (v.64, #2)
Toxicology of nanoparticles by Andreas Elsaesser; C. Vyvyan Howard (pp. 129-137).
While nanotechnology and the production of nanoparticles are growing exponentially, research into the toxicological impact and possible hazard of nanoparticles to human health and the environment is still in its infancy. This review aims to give a comprehensive summary of what is known today about nanoparticle toxicology, the mechanisms at the cellular level, entry routes into the body and possible impacts to public health.Proper characterisation of the nanomaterial, as well as understanding processes happening on the nanoparticle surface when in contact with living systems, is crucial to understand possible toxicological effects. Dose as a key parameter is essential in hazard identification and risk assessment of nanotechnologies. Understanding nanoparticle pathways and entry routes into the body requires further research in order to inform policy makers and regulatory bodies about the nanotoxicological potential of certain nanomaterials.Display Omitted
Keywords: Nanotoxicology; Nanoparticle characterisation; Surface; Dose; Agglomeration; Reactive oxygen; Inflammation; Entry routes; Risk assessment; Hazard identification
Luminescent quantum dots as platforms for probing in vitro and in vivo biological processes by Hedi Mattoussi; Goutam Palui; Hyon Bin Na (pp. 138-166).
In this report we review some of the recent progress made for enhancing the biocompatibility of luminescent quantum dots (QDs) and for developing targeted bio-inspired applications centered on live cell imaging and sensing. We start with a detailed analysis of the surface functionalization strategies developed thus far, and discuss their effectiveness for providing long term stability of the quantum dots in biological media, to changes in pH and to added electrolytes. We then discuss the available conjugation techniques to couple QDs to a variety of biological receptors and compare their effectiveness. In particular, we highlight the implementation of new strategies such as the use of copper-free cyclo-addition reaction(CLICK) chemistry and chemo-selective ligation. We then discuss the advances made for intracellular delivery where ideas such as receptor-driven endocytosis and uptake promoted by cell penetrating peptides are used. We then describe a few representative examples where QDs have been used to investigate specific cell biology processes. Such processes include binding of QDs conjugated to the nerve growth factor to membrane specific receptors and intracellular uptake, tracking of membrane protein at the single molecule level, and recognition of ligand bound QDs by T cell receptors. We conclude by discussing issues of toxicity associated with the use of QDs in biology.Display Omitted
Keywords: Quantum dots; Synthesis; Coupling chemistry; Bioconjugates; Imaging; Endocytosis; Protein interaction
Quantum dots to tail single bio-molecules inside living cells by Paolo Pierobon; Giovanni Cappello (pp. 167-178).
In the last two decades, the single particle and single molecule approach became more and more popular to investigate the activity and the mechano-chemical properties of biological molecules. The inherent limit of these assays was that the molecules of interest were observed in vitro, out of their natural environment, the cell. Several recent works have shown the possibility to overcome this limit, to extend this approach to living cells and to observe the details of many cellular processes at the molecular level.In this review we discuss the use of semiconductor quantum dots to perform single particle and single molecule tracking in the cell. We refer to other articles for the technical aspects of this method. Here, after an introduction on the advantages provided by these nanoparticles, we restrict ourselves to some examples, mainly related to intracellular transport and molecular motor activity. These will illustrate the important role played by semiconductor quantum dots as fluorescent nano-reporters in in cell single molecule approach in modern biology and biophysics.Display Omitted
Keywords: Single molecule; Quantum dots; Nanoparticle tracking; Live cell; Intracellular transport
Physico-chemical parameters that govern nanoparticles fate also dictate rules for their molecular evolution by Sandrine Dufort; Lucie Sancey; Jean-Luc Coll (pp. 179-189).
Nanoparticles are efficient to safely deliver therapeutic and imaging contrast agents to tumors for cancer diagnostic and therapy, if they can escape the reticuloendothelial system (RES) and accumulate in tumors either passively due to the enhanced permeability and retention (EPR) effect or actively via a specific ligand. The main hallmark of nanoparticles is their large surface areas, which, depending of their chemical compositions, surface coatings, electric charges, sizes and shapes, will generate complex, extremely dynamic and continuous interactions and exchanges between the nanoparticles and the different molecules present in the blood. Special attention will be paid to explain how the nanoparticles were improved step by step in order to adapt our increasing knowledge on their biophysics. In particular, we will discuss the influence of PEGylation, the difficulties to generate actively targeted particles and finally the actual trends in the manufacturing of “third-generation” smart particles.Display Omitted
Keywords: Abbreviations; RES; reticuloendothelial system; EPR; enhanced permeability and retention effect; FDA; Food and Drug Administration; PEG; polyethylene glycol; HSA; human serum albumin; HDL; high-density lipoprotein; MDS; multistage delivery system; siRNA; small interfering RNA; MSN; end-capped mesoporous silica nanoparticle; SPION; superparamagnetic iron oxide nanoparticlesNanovectors; Tissue distribution; EPR effect; Targeted nanoparticles; Drug delivery system; PEGylation; Particle size; Particle shape; Protein binding
Gold nanorods: Their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions by Alaaldin M. Alkilany; Lucas B. Thompson; Stefano P. Boulos; Patrick N. Sisco; Catherine J. Murphy (pp. 190-199).
Gold nanorods have promising applications in the fields of drug delivery and photothermal therapy. These promises arise from the nanorods' unique optical and photothermal properties, the availability of synthetic protocols that can tune the size and shape of the particles, the ability to modify the surface and conjugate drugs/molecules to the nanorods, and the relative biocompatibility of gold nanorods. In this review, current progress in using gold nanorods as phototherapeutic agents and as drug delivery vehicles is summarized. Issues of dosage, toxicity and biological interactions at three levels (biological media alone; cells; whole organisms) are discussed, concluding with recommendations for future work in this area.Display Omitted
Keywords: Gold nanorods; Drug delivery; Photothermal therapy; Bioconjugation; Surface modification; Cellular uptake; Toxicity
Monolayer coated gold nanoparticles for delivery applications by Subinoy Rana; Avinash Bajaj; Rubul Mout; Vincent M. Rotello (pp. 200-216).
Gold nanoparticles (AuNPs) provide attractive vehicles for delivery of drugs, genetic materials, proteins, and small molecules. AuNPs feature low core toxicity coupled with the ability to parametrically control particle size and surface properties. In this review, we focus on engineering of the AuNP surface monolayer, highlighting recent advances in tuning monolayer structures for efficient delivery of drugs and biomolecules. This review covers two broad categories of particle functionalization, organic monolayers and biomolecule coatings, and discusses their applications in drug, DNA/RNA, protein and small molecule delivery.Display Omitted
Keywords: Gold; Nanoparticles; Monolayer; Delivery; Organic monolayer; Biomolecule coated; DNA; Drug delivery; Protein; Small molecule