Showing papers by "Dean Ho published in 2011"

Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment

Abstract: Enhancing chemotherapeutic efficiency through improved drug delivery would facilitate treatment of chemoresistant cancers, such as recurrent mammary tumors and liver cancer. One way to improve drug delivery is through the use of nanodiamond (ND) therapies, which are both scalable and biocompatible. Here, we examined the efficacy of an ND-conjugated chemotherapeutic in mouse models of liver and mammary cancer. A complex (NDX) of ND and doxorubicin (Dox) overcame drug efflux and significantly increased apoptosis and tumor growth inhibition beyond conventional Dox treatment in both murine liver tumor and mammary carcinoma models. Unmodified Dox treatment represents the clinical standard for most cancer treatment regimens, and NDX had significantly decreased toxicity in vivo compared to standard Dox treatment. Thus, ND-conjugated chemotherapy represents a promising, biocompatible strategy for overcoming chemoresistance and enhancing chemotherapy efficacy and safety.

Multimodal nanodiamond drug delivery carriers for selective targeting, imaging, and enhanced chemotherapeutic efficacy.

Abstract: The advancement of next-generation nanocarriers as drug delivery platforms will require the incorporation of these useful properties, through which adverse side effects of chemotherapy drugs can be avoided and overall treatment and diagnosis improved. As such, a variety of nanoparticle-based delivery systems have already been widely investigated and provided interesting avenues of research for improving cancer treatments through therapy and targeted delivery. [ 2–7 ]

Strategy for increasing drug solubility and efficacy through covalent attachment to polyvalent DNA-nanoparticle conjugates.

Abstract: Paclitaxel, a potent chemotherapeutic utilized in a variety of cancers, can be limited in its effectiveness due to inherent insolubility in aqueous media and acquired chemoresistance within certain cells. An approach has been developed for increasing Paclitaxel solubility and effectiveness by covalent attachment to gold nanoparticles via DNA linkers. The resulting conjugates are highly soluble in aqueous buffer, exhibiting greater than a 50-fold increase in solubility over the unconjugated drug. DNA linkers are labeled with a fluorophore, which affords a convenient means of visualizing resultant conjugates within cells. Internalized conjugates demonstrate increased activity as compared with free drug across a variety of cell types, including a Paclitaxel-resistant cell line. Attachment to DNA–nanoparticle conjugates may become a general strategy for solubilizing and enhancing a wide variety of therapeutic agents in aqueous media.

Atomistic simulation and measurement of pH dependent cancer therapeutic interactions with nanodiamond carrier.

Abstract: In this work, we have combined constant-pH molecular dynamics simulations and experiments to provide a quantitative analysis of pH dependent interactions between doxorubicin hydrochloride (DOX) cancer therapeutic and faceted nanodiamond (ND) nanoparticle carriers. Our study suggests that when a mixture of faceted ND and DOX is dissolved in a solvent, the pH of this solvent plays a controlling role in the adsorption of DOX molecules on the ND. We find that the binding of DOX molecules on ND occurs only at high pH and requires at least ∼10% of ND surface area to be fully titrated for binding to occur. As such, this study reveals important mechanistic insight underlying an ND-based pH-controlled therapeutic platform.

Triggered release of therapeutic antibodies from nanodiamond complexes

Abstract: Recent reports have revealed that detonation nanodiamonds (NDs) can serve as efficient, biocompatible, and versatile drug delivery platforms. Consequently, further investigations exploring additional therapeutic applications are warranted. Current limitations associated with the non-specific nature of intravenous drugs limit the potential of certain pharmacological agents. One such treatment that could benefit from a stable delivery platform is antibody (Ab) therapy. Determination of Ab adsorption and desorption to a ND surface was subsequently examined using the transforming growth factor β (TGF-β) antibody as a model therapeutic. ND–Ab complexes were found to be stable in water through enzyme-linked immunosorbent assays (ELISAs), UV-vis spectroscopy and TEM, with no Ab released after ten days. Released Abs were detected in extreme pH solutions (3.5), DMEM (+) serum with pH levels ranging from 4 to 10.5, and inorganic saline solutions. Preserved activity of Abs released in DMEM (+) serum was confirmed using an ELISA. These results suggest ND–Ab complexes are synthesized and stabilized in water and are triggered to release active Abs upon exposure to physiological conditions.

Paramagnetic metal-nanodiamond conjugates

Abstract: The present invention provides compositions and methods for the synthesis of conjugates of paramagnetic metal ions and nanodiamonds, and uses thereof. In particular, the present invention provides synthesis of paramagnetic metal-nanodiamond conjugates and methods using such compositions as molecular imaging probes.

Thomson Reuters: Cause for Celebration!

Abstract: T he news that JALA was accepted for indexing by Thomson’s Journal Citation Reports marked another important milestone in JALA’s evolution and is a testament to the quality and commitment of the many scientific professionals who fuel JALA’s vision and craft its reality. Without being asked to complete the application process, JALA was added to Thomson Reuters Science Citation Index Expanded (also known as SciSearch), Journal Citation Reports/Science Edition, Biological Abstracts, and BIOSIS Previews. This means that as of the beginning of this year, Thomson is tracking citations of JALA articles published in 2009 and 2010, and JALA’s first impact factor will be announced in June of 2012. Is this exciting news? Yes! Is this cause for celebration? Definitely! Having an impact factor is important to JALA and its authors. As I am sure most of you know, a journal’s impact factor indicates the average number of citations of articles published in a journal. Many regard this as a measure of relevance for individual journals within their respective fields. But there’s more to this story. This well deserved recognition by the scientific publishing community is a huge pat on the back for the hundreds of authors, manuscript reviewers, guest editors, executive editors, and editorial board members who worked so hard over the years to get JALA to this point. It was, however, the SLAS spirit of community not publishing milestones that kept their engines running. At the foundation of JALA’s recent success is the broad spectrum of fundamental and applied innovation that JALA has featured during the past years

Multiscale framework for biomedical simulation from molecular dynamics to continuum mechanics

Abstract: In biomedical engineering, computational mechanics has played an important role in understanding complex systems such as drug delivery platforms, biosensors and blood flow. In situations where a clinical test is either prohibitively difficult or required understaning, numerical experiments offer an effective way to gain important insight. For this reason computational methods have become essential tools for biomedical problems. In this paper, the multiscale framework for biomedical simulation is shown by applying various computational methods to several biomedical problems. To show the variety and breadth of the biomedical problems that can be addressed through computation, we describe several numerical methods that are capable of addressing the multiscale, multiphysics problems found in biological systems, and motivate each with sample applications. Specifically, molecular dynamics (MD), dissipate particle dynamics (DPD), elastic network model (ELM) and immersed molecular electrokinetic finite element method (IMEFEM) are introduced with state-of-the-art research topics in biotechnology.

The 2011 JALA Ten

Abstract: Figure 1. Image reprinted with permission from Macmillan Publishers Ltd: Nature Medicine. Sullivan, S. P., et al., Dissolving polymer microneedle patches for influenza vaccination. Nat. Med. 2010, 16(8), 915e920, doi:10.1038/nm.2182. During the past year, the JALA Editorial Board requested nominations for The JALA Ten in an effort to highlight the top 10 breakthroughs of the year that are making an impact on a diverse set of fields in biology and medicine. Following a selection process based on the expertise of internationally recognized authorities in automation, microfluidics, drug screening and delivery, and diagnostics, we are proud to announce The 2011 JALA Ten honorees. These discoveries represent the efforts of researchers from all over the world and cover disciplines that range from nanomaterials to drug delivery and pathogen detection. Covering the best in multidisciplinary research serves as a foundation for JALA, and we are proud to recognize the work that is inspiring the next generation of medical advances.