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1.  Synthesis and characterization of membrane stable bis(arylimino)isoindole dyes and their potential application in nano-biotechnology 
Tetrahedron letters  2012;53(32):4134-4137.
A synthetic methodology of preparing novel membrane stable, responsive dyes is revealed in this manuscript. 1,3-bis(arylimino)isoindole dyes were synthesized and their properties to undergo intramolecular hydrogen bonding was studied with fluorescence spectroscopy in varying solvent polarities. Based on the functional moieties, compound that is capable of hydrogen donor and acceptor interactions produces predominant photoexcitation in comparison to the responsive dyes that lack these functionalities. These dyes, by the virtue of the presence of long chain acyl groups could be incorporated stably within the phospholipids membrane of core-shell nanoparticles. Nanoparticle was ‘cracked’ to release the dye from a hydrophobic to a hydrophilic environment, A significant change in florescence intensity was then observed, indicating the direct change in effect of intramolecular hydrogen bonding based on solvent polarity changes. This unique study provided implications of many further applications towards nanomedicine and nano-biotechnology.
PMCID: PMC3398693  PMID: 22822276
Fluorescence dye; Bis(imino)isoindole; Responsive dyes; Membrane stable; Nano-biotechnology
2.  Antiangiogenic nanotherapy with lipase-labile Sn-2 fumagillin prodrug 
Nanomedicine (London, England)  2012;7(10):1507-1519.
The chemical instability of antiangiogenic fumagillin, combined with its poor retention during intravascular transit, requires an innovative solution for clinical translation. We hypothesized that an Sn-2 lipase-labile fumagillin prodrug in combination with a contact-facilitated drug delivery mechanism, could be used to address these problems.
αvβ3-targeted and nontargeted nanoparticles with and without fumagillin in the prodrug or native forms were evaluated in vitro and in vivo in the Matrigel™ (BD Biosciences, CA, USA) plug model of angiogenesis in mice.
In vitro experiments demonstrated that the new fumagillin prodrug decreased viability at least as efficacious as the parent compound, on an equimolar basis. In the Matrigel mouse angiogenesis model, αvβ3-fumagillin prodrug decreased angiogenesis as measured by MRI (3T), while the neovasculature was unaffected with the control nanoparticles.
The present approach resolved the previously intractable problems of drug instability and premature release in transit to target sites.
PMCID: PMC3498609  PMID: 22709347
angiogenesis; fumagillin; nanomedicine; nanoparticle; prodrug; therapy
3.  Sensitive Biological Detection with a Soluble and Stable Polymeric Paramagnetic Nano Cluster 
Journal of the American Chemical Society  2012;134(25):10377-10380.
We describe the design, synthesis and biological characterization of manganese oxocluster-based “single molecule magnets (SMMs)”. We demonstrate that polymeric micellar nanoparticles can serve as a carrier and help to stabilize delicate SMM molecules from breaking down easily and thus prevent their property loss. Concentrating thousands of Mn-clusters per micelle provided a high ionic and per-particle relaxivity allowing sensitive MR imaging in vivo. This reports one of the earliest examples of in vivo imaging of a rationally designed polymeric micelles that features SMM.
PMCID: PMC3397310  PMID: 22693958
4.  Influence of Patient Preferences on the Cost-Effectiveness of Screening for Lynch Syndrome 
Journal of Oncology Practice  2012;8(3 Suppl):e24s-e30s.
This cost-utility analysis reports on the effect of quality of life on the value of screening all new patients with colorectal cancer for Lynch syndrome.
Patients and relatives have varying preferences for genetic testing and interventions related to hereditary cancer syndromes. We examined how the impact of these services on quality of life (QoL) affects the cost-effectiveness of screening for Lynch syndrome among probands newly diagnosed with colorectal cancer and their relatives.
We constructed a state-transition model comparing screening strategies (clinical criteria, prediction algorithms, tumor testing, and upfront germline testing) with no screening to identify Lynch syndrome. The model incorporated individuals' health state utilities after screening, germline testing, and risk-reducing surgeries, with utilities persisting for 12 months in the base case. Outcomes consisted of quality-adjusted life-years (QALYs), costs, and cost per QALY gained. Sensitivity analyses assessed how the duration and magnitude of changes in QoL influenced results.
Multiple screening strategies yielded gains in QALYs at acceptable costs compared with no screening. The preferred strategy—immunohistochemistry of tumors followed by BRAF mutation testing (IHC/BRAF)—cost $59,700 per QALY gained in the base case. The duration and magnitude of decreases in QoL after decisions related to germline testing and surgeries were key determinants of the cost-effectiveness of screening. IHC/BRAF cost > $100,000 per QALY gained when decrements to QoL persisted for 21 months.
Screening for Lynch syndrome in the population is likely to yield long-term gains in life expectancy that outweigh any short-term decreases in QoL, at acceptable costs. Counseling for individuals should aim to mitigate potential negative impact of genetic testing and risk-reducing interventions on QoL.
PMCID: PMC3348599  PMID: 22942831

Results 1-4 (4)