Gold Nanoparticle-Based Fluorescent Contrast Agent with Enhanced Sensitivity.

Gold nanoparticle (GNP) based contrast agents that are highly specific and sensitive for both optical and X-ray/CT imaging modalities are being developed for detecting the cancer expressing nucleolin and matrix metallo-proteinase 14 (MMP-14) on the cell membrane: Nucleolin is normally present in the nucleus. For many cancer cells, however, it is over-expressed on the cell membrane, having it to be a good cancer marker. Aptamer AS1411 is known to be an excellent target for nucleolin and also known to treat several cancer types; and MMP-14 in cancer is involved in tumor angiogenesis, blood vessel re-organization, and metastasis. In the proposed agent, AS1411 is selected as the cancer targeting molecule; and the unique property of GNPs of modulating fluorescence are utilized to allow the agent to trigger its fluorescence upon reacting with MMP-14, at an enhanced fluorescence level. GNPs are also natural X-ray/CT contrast agent. Here, as a part of on-going development of the dual-modality contrast agent, we report that conjugating a safe, NIR fluorophore Cypate at a precisely determined distance from the GNP enhanced the Cypate fluorescence up to two times. In addition, successful conjugation of the nucleolin target AS1411 onto the GNP was confirmed and among the GNPs size range 5-30 nm tested, 10 nm GNPs showed the highest X-ray/CT enhancement.

Conditionally activating optical contrast agent with enhanced sensitivity via gold nanoparticle plasmon energy transfer: feasibility study.

BACKGROUND: Molecular sensing/imaging utilizing fluorophores has been one of the most frequently used techniques in biomedical research. As for any molecular imaging techniques, fluorescence mediated sensing always seeks for greater specificity and sensitivity. Since fluorophores emit fluorescence while their electron energy state changes, manipulating the local electromagnetic field around the fluorophores may be a way to enhance the specificity and sensitivity. Gold nanoparticles (GNPs) are known to form a very strong electromagnetic field on their surface [i.e., surface plasmon field (SPF)], upon receiving photonic energy. The level of fluorescence change by GNP-SPF may range from complete quenching to extensive enhancement, depending upon the SPF strength, excitation and emission wavelengths, and quantum yield of the fluorophore. METHOD: Here, we report a novel design that utilizes BOTH fluorescence quenching and enhancement abilities of the GNP in one single nano-entity, providing high specificity and sensitivity. The construct utilizes a specially designed molecular dual-spacer that places the fluorphore at the location with an appropriate GNP-SFP strength before and after exposed to the biomarker. A model system to test the concept was an optical signal mediator activated by urokinase-type plasminogen activator (uPA; breast cancer secreting enzyme). RESULTS: The resulting contrast agent shows less than 10% of the natural fluorescence but, in the presence of uPA, its fluorescence emission is triggered and emits its fluorescence approximately twice of the natural form. CONCLUSION: This study demonstrated that our novel design of an optical contrast agent can be conditionally activated with enhanced sensitivity, using both quenching and enhancement phenomena of fluorophores in the electromagnetic field of the appropriate strengths (in this case, locally generated by the GNP-SPF). This entity is similar to molecular beacon in terms of specificity but with greater sensitivity. In addition, it is not restricted to only DNA or RNA sensing but for any designs that cause the change in the distance between the fluorophore and GNP, upon the time of encountering biomarker of interest.

Historical observations on the half-century freeze in research between the Bonghan system and the primo vascular system.

This article provides potential reasons for the past 45-year halt in research between the time of the Bonghan system of Bong Han Kim (B.H. Kim) and that of the primo vascular system (PVS) of Kwang-Sup Soh (K.S. Soh), briefly but more accurately in its history. Over the years, numerous questions related to the Bonghan system and the PVS have arisen, especially from researchers interested in pursuing PVS research: When and how did B.H. Kim's study results on the Bonghan system become known to public? Why did B.H. Kim and his publications disappear after 1966? Why was little study performed on the system for almost 50 years after Kim? Why and how was the research on the system reinitiated in 2002 by Kwang-Sup Soh? Why did the Bonghan system become the PVS? These questions, as well as technical difficulties in identifying the system, have discouraged many researchers from becoming involved in research on the system. The motivation for preparing this article was to remove doubts about the existence of this important organ, which might have been caused by its unusual and unclear historical background, by providing an accurate history.