Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).

Stimuli-responsive nanocarriers for drug delivery

Chemistries that Facilitate Nanotechnology Kim E. Sapsford,† W. Russ Algar, Lorenzo Berti, Kelly Boeneman Gemmill,‡ Brendan J. Casey,† Eunkeu Oh, Michael H. Stewart, and Igor L. Medintz*,‡ †Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States ‡Center for Bio/Molecular Science and Engineering Code 6900 and Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States Sotera Defense Solutions, Crofton, Maryland 21114, United States

Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology.

Gold nanoparticles (AuNPs) are important components for biomedical applications. AuNPs have been widely employed for diagnostics, and have seen increasing use in the area of therapeutics. In this mini-review, we present fabrication strategies for AuNPs and highlight a selection of recent applications of these materials in bionanotechnology.

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Gold nanoparticles: preparation, properties, and applications in bionanotechnology.

Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the cell and mitochondrial membrane potentials, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this Review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

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Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

A living radical polymerization (LRP) is a free radical polymerization that aims at displaying living character, (i.e., does not terminate or transfer and is able to continue polymerization once the initial feed is exhausted by addition of more monomer). However, termination reactions are inherent to a radical process, and modern LRP techniques seek to minimize such reactions, therefore providing control over the molecular weight and the molecular weight distribution of a polymeric material. In addition, the better LRP techniques incorporate many of the desirable features of traditional free radical polymerization, such as compatibility with a wide range of monomers, tolerance of many functionalities, and facile reaction conditions. The control of molecular weight and molecular weight distribution has enabled access to complex architectures and site specific functionality that were previously impossible to achieve via traditional free radical polymerizations. These LRPs are classified in three different subgroups: (1) stable free-radical polymerization such as nitroxide mediated polymerization (NMP),1,2 (2) degenerative transfer polymerization, such as iodine transfer polymerization (ITP and RITP),3,4 single electron transfer-degenerative transfer living radical polymerization(SET-DTLRP),5,6reversibleaddition-fragmentation chain transfer (RAFT),7,8 and macromolecular design via the interchange of xanthates (MADIX)9,10 polymerization, and (3) metal mediated catalyzed polymerization, such as atom transfer radical polymerization (ATRP),11-14 single electron transfer-living radical polymerization (SET-LRP),15 and organotellurium mediated living radical polymrization16-19 Among the existing LRP techniques, RAFT and MADIX are probably the most versatile processes, as they are tolerant * E-mail: T.P.D., T.Davis@UNSW.edu.au; S.P., S.Perrier@ chem.usyd.edu.au. † Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences & Engineering, UNSW. ‡ Centre for Advanced Macromolecular Design (CAMD), School of Biotechnology & Biomolecular Sciences, UNSW. § The University of Sydney. Chem. Rev. 2009, 109, 5402–5436 5402

Bioapplications of RAFT polymerization.

ConspectusMitochondria are organelles with critical roles in key processes within eukaryotic cells, and their dysfunction is linked with numerous diseases including neurodegenerative disorders and cancer. Pharmacological manipulation of mitochondrial function is therefore important both for basic science research and eventually, clinical medicine. However, in comparison to other organelles, mitochondria are difficult to access due to their hydrophobic and dense double membrane system as well as their negative membrane potential.To tackle the challenge of targeting these important subcellular compartments, significant effort has been put forward to develop mitochondria-targeted systems capable of transporting bioactive cargo into the mitochondrial interior. Systems now exist that utilize small molecule, peptide, liposome, and nanoparticle-based transport. The vectors available vary in size and structure and can facilitate transport of a variety of compounds for mitochondrial delivery. Notably, peptide-base...

Marya Ahmed

Papers

Peptide-Mediated Delivery of Chemical Probes and Therapeutics to Mitochondria

The effect of polymer architecture, composition, and molecular weight on the properties of glycopolymer-based non-viral gene delivery systems

Progress of RAFT based polymers in gene delivery

Biotinylated Glyco-Functionalized Quantum Dots: Synthesis, Characterization, and Cytotoxicity Studies

The effect of molecular weight, compositions and lectin type on the properties of hyperbranched glycopolymers as non-viral gene delivery systems