Devika B. Chithrani

Bio: Devika B. Chithrani is an academic researcher from University of Victoria. The author has contributed to research in topics: Colloidal gold & Quantum dot. The author has an hindex of 19, co-authored 46 publications receiving 1848 citations. Previous affiliations of Devika B. Chithrani include BC Cancer Agency & St. Michael's Hospital.

Gold Nanoparticles as Radiation Sensitizers in Cancer Therapy

Abstract: Among other nanoparticle systems, gold nanoparticles have been explored as radiosensitizers. While most of the research in this area has focused on either gold nanoparticles with diameters of less than 2 nm or particles with micrometer dimensions, it has been shown that nanoparticles 50 nm in diameter have the highest cellular uptake. We present the results of in vitro studies that focus on the radiosensitization properties of nanoparticles in the size range from 14–74 nm. Radiosensitization was dependent on the number of gold nanoparticles internalized within the cells. Gold nanoparticles 50-nm in diameter showed the highest radiosensitization enhancement factor (REF) (1.43 at 220 kVp) compared to gold nanoparticles of 14 and 74 nm (1.20 and 1.26, respectively). Using 50-nm gold nanoparticles, the REF for lower- (105 kVp) and higher- (6 MVp) energy photons was 1.66 and 1.17, respectively. DNA double-strand breaks were quantified using radiation-induced foci of γ-H2AX and 53BP1, and a modest incr...

Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization.

Abstract: The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Intracellular uptake, transport, and processing of gold nanostructures.

Abstract: The emerging field of nanomedicine requires better understanding of the interface between nanotechnology and medicine Better knowledge of the nano-bio interface will lead to better tools for diagnostic imaging and therapy In this review, recent progress in understanding of how size, shape, and surface properties of nanoparticles (NPs) affect intracellular fate of NPs is discussed Gold nanostructures are used as a model system in this regard since their physical and chemical properties can be easily manipulated The NP-uptake is dependent on the physiochemical properties, and once in the cell, most of the NPs are trafficked via an endo-lysosomal path followed by a receptor-mediated endocytosis process at the cell membrane Within the size range of 2-100 nm, Gold nanoparticles (GNPs) of diameter 50 nm demonstrate the highest uptake Cellular uptake studies of gold nanorods (GNRs) show that there is a decrease in uptake as the aspect ratio of GNRs increases Theoretical models support the size- and shape-dependent NP-uptake The intracellular transport of targeted NPs is faster than untargeted NPs The surface ligand and charge of NPs play a bigger role in their uptake, transport, and organelle distribution Exocytosis of NPs is dependent on size and shape as well; however, the trend is different compared to endocytosis GNPs are now being incorporated into polymer and lipid based NPs to build multifunctional devices A multifunctional platform based on gold nanostructures, with multimodal imaging, targeting, and therapeutics; hold the possibility of promising directions in medical research

Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

Abstract: The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.

Biological applications of magnetic nanoparticles

Abstract: In this review an overview about biological applications of magnetic colloidal nanoparticles will be given, which comprises their synthesis, characterization, and in vitro and in vivo applications. The potential future role of magnetic nanoparticles compared to other functional nanoparticles will be discussed by highlighting the possibility of integration with other nanostructures and with existing biotechnology as well as by pointing out the specific properties of magnetic colloids. Current limitations in the fabrication process and issues related with the outcome of the particles in the body will be also pointed out in order to address the remaining challenges for an extended application of magnetic nanoparticles in medicine.

Gold nanoparticles as novel agents for cancer therapy

Abstract: Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.

Endocytosis at the nanoscale

Abstract: Endocytosis is a fundamental process in which eukaryotic cells internalise molecules and macromolecules via deformation of the membrane and generation of membrane-bound carriers. Functional aspects are not only limited to uptake of nutrients, but also play a primary role in evolutionary conserved processes such as the regulation of plasma membrane protein activity (i.e. signal-transducing receptors, small-molecule transporters and ion channels), cell motility and mitosis. The macromolecular nature of the material transported by endocytosis makes this route one of the most important targets for nanomedicine. Indeed, many nanoparticle formulations have been customised to enter cells through endocytosis and deliver the cargo within the cell. In this critical review, we present an overview of the biology of endocytosis and discuss its implications in cell internalisation of nanoparticles. We discuss how nanoparticle size, shape and surface chemistry can control this process effectively. Finally, we discuss different drug delivery strategies on how to evade lysosomal degradation to promote effective release of the cargo (376 references).