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Advanced Drug Delivery Reviews (v.62, #6)

Editorial Board (pp. ii).

Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates by Jung Heon Lee; Mehmet V. Yigit; Debapriya Mazumdar; Yi Lu (pp. 592-605).
Recent progress in an emerging area of designing aptamer and nanomaterial conjugates as molecular diagnostic and drug delivery agents in biomedical applications is summarized. Aptamers specific for a wide range of targets are first introduced and compared to antibodies. Methods of integrating these aptamers with a variety of nanomaterials, such as gold nanoparticles, quantum dots, carbon nanotubes, and superparamagnetic iron oxide nanoparticles, each with unique optical, magnetic, and electrochemical properties, are reviewed. Applications of these systems as fluorescent, colorimetric, magnetic resonance imaging, and electrochemical sensors in medical diagnostics are given, along with new applications as smart drug delivery agents.

Keywords: DNA; Aptamer; Nanomaterials; Diagnostics; Biosensor; Drug delivery; Biomedical; Targeted therapeutics


DNA nanomedicine: Engineering DNA as a polymer for therapeutic and diagnostic applications by Michael J. Campolongo; Shawn J. Tan; Jianfeng Xu; Dan Luo (pp. 606-616).
Nanomedicine, the application of nanotechnology to medicine, encompasses a broad spectrum of fields including molecular detection, diagnostics, drug delivery, gene regulation and protein production. In recent decades, DNA has received considerable attention for its functionality and versatility, allowing it to help bridge the gap between materials science and biological systems. The use of DNA as a structural nanoscale material has opened a new avenue towards the rational design of DNA nanostructures with different polymeric topologies. These topologies, in turn, possess unique characteristics that translate to specific therapeutic and diagnostic strategies within nanomedicine.

Keywords: DNA; Nanomedicine; Polymer topologies; Nano-assembly; DNA nanostructures


DNA Self-assembly for Nanomedicine by Rahul Chhabra; Jaswinder Sharma; Yan Liu; Sherri Rinker; Hao Yan (pp. 617-625).
Self-assembling DNA nanostructures based on rationally designed DNA branch junction molecules has recently led to the construction of patterned supramolecular structures with increased complexities. An intrinsic value of DNA tiles and patterns lies in their utility as molecular pegboard for deterministic positioning of molecules or particles with accurate distance and architectural control. This review will discuss the state-of-art developments in self-assembled DNA nanostructural system. Biomedical aspects of information guided DNA nanostructures will also be summarized. We illustrate both the use of simple DNA artworks for sensing, computation, drug delivery and the application of more complex DNA architectures as scaffolds for the construction of protein and nanoparticle arrays.

Keywords: Self-assembly; DNA Nanotechnology; DNA tiles; DNA nanoarrays; Biosensing


DNA-based nano-sized systems for pharmaceutical and biomedical applications by Makiya Nishikawa; Sakulrat Rattanakiat; Yoshinobu Takakura (pp. 626-632).
DNA is one of the most important components for all living organisms and many species, including humans, use DNA to store and transmit genetic information to new generations. Recent advances in the handling of DNA have made it possible to use DNA as a building block of nano-sized materials with precisely designed architectures. Although various approaches have been proposed to obtain DNA assemblies with designed architecture in the nano- to micrometer range, there is little information about their interaction with biological components, including target molecules. Understanding the interaction between DNA assemblies and the body is highly important for successful pharmaceutical and biomedical applications. Here, we first review the basic aspects of externally administered DNA molecules, including the stability, permeability and delivery issues. Then, we discuss the unique responses observed in the interaction of structured DNA assemblies and cells expressing Toll-like receptor-9, the receptor responsible for the recognition of unmethylated CpG dinucleotides that are abundant in the DNA of invading pathogens, such as bacteria and viruses.

Keywords: DNA; Nano-assembly; Drug delivery; Innate immunity; Toll-like receptor; CpG motif


DNA and carbon nanotubes as medicine by William Cheung; Francesco Pontoriero; Oleh Taratula; Alex M. Chen; Huixin He (pp. 633-649).
The identification of disease-related genes and their complete nucleotide sequence through the human genome project provides us with a remarkable opportunity to combat a large number of diseases with designed genes as medicine. However, gene therapy relies on the efficient and nontoxic transport of therapeutic genetic medicine through the cell membranes, and this process is very inefficient. Carbon nanotubes, due to their large surface areas, unique surface properties, and needle-like shape, can deliver a large amount of therapeutic agents, including DNA and siRNAs, to the target disease sites. In addition, due to their unparalleled optical and electrical properties, carbon nanotubes can deliver DNA/siRNA not only into cells, which include difficult transfecting primary-immune cells and bacteria, they can also lead to controlled release of DNA/siRNA for targeted gene therapy. Furthermore, due to their wire shaped structure with a diameter matching with that of DNA/siRNA and their remarkable flexibility, carbon nanotubes can impact on the conformational structure and the transient conformational change of DNA/RNA, which can further enhance the therapeutic effects of DNA/siRNA. Synergistic combination of the multiple capabilities of carbon nanotubes to deliver DNA/siRNAs will lead to the development of powerful multifunctional nanomedicine to treat cancer or other difficult diseases. In this review, we summarized the current studies in using CNT as unique vehicles in the field of gene therapy.

Keywords: Gene therapy; Nonviral delivery; Multifunctional; Near infrared fluorescence (NIR); Raman; Carbon nanotubes; Single walled carbon nanotubes (SWNTs); Multiwalled carbon nanotubes (MWNTs); DNA; Small interference RNA (siRNA)


Engineering RNA for Targeted siRNA Delivery and Medical Application by Peixuan Guo; Oana Coban; Nicholas M. Snead; Joe Trebley; Steve Hoeprich; Songchuan Guo; Yi Shu (pp. 650-666).
RNA engineering for nanotechnology and medical applications is an exciting emerging research field. RNA has intrinsically defined features on the nanometre scale and is a particularly interesting candidate for such applications due to its amazing diversity, flexibility and versatility in structure and function. Specifically, the current use of siRNA to silence target genes involved in disease has generated much excitement in the scientific community. The intrinsic ability to sequence-specifically downregulate gene expression in a temporally- and spatially controlled fashion has led to heightened interest and rapid development of siRNA-based therapeutics. Although methods for gene silencing have been achieved with high efficacy and specificity in vitro, the effective delivery of nucleic acids to specific cells in vivo has been a hurdle for RNA therapeutics. This article covers different RNA-based approaches for diagnosis, prevention and treatment of human disease, with a focus on the latest developments of non-viral carriers of siRNA for delivery in vivo. The applications and challenges of siRNA therapy, as well as potential solutions to these problems, the approaches for using phi29 pRNA-based vectors as polyvalent vehicles for specific delivery of siRNA, ribozymes, drugs or other therapeutic agents to specific cells for therapy will also be addressed.

Keywords: Viral DNA packaging motor; RNA dimer; Trimer; Hexameric ring; DNA translocation; Bacteriophage phi29; pRNA; Procapsid; Viral assembly; siRNA; Targeted delivery; Gene therapy; RNA nanotechnology; Nanobiotechnology; Nanomedicine
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