Conditionally Activating Optical Contrast Agent with Enhanced Sensitivity Via Gold Nanoparticle Plasmon Energy Transfer: Feasibility Study

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2014 Dec 8

PMID 25481683

Citations 1

Authors

Kyung Aih Kang

Jianting Wang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Recent advances in light-responsive on-demand drug-delivery systems.

Linsley C, Wu B Ther Deliv. 2017; 8(2):89-107.

PMID: 28088880 PMC: 5561969. DOI: 10.4155/tde-2016-0060.

References

Reineck P, Gomez D, Ng S, Karg M, Bell T, Mulvaney P . Distance and wavelength dependent quenching of molecular fluorescence by Au@SiO2 core-shell nanoparticles. ACS Nano. 2013; 7(8):6636-48. DOI: 10.1021/nn401775e. View

Pleijhuis R, Langhout G, Helfrich W, Themelis G, Sarantopoulos A, Crane L . Near-infrared fluorescence (NIRF) imaging in breast-conserving surgery: assessing intraoperative techniques in tissue-simulating breast phantoms. Eur J Surg Oncol. 2010; 37(1):32-9. DOI: 10.1016/j.ejso.2010.10.006. View

Lakowicz J . Radiative decay engineering 5: metal-enhanced fluorescence and plasmon emission. Anal Biochem. 2005; 337(2):171-94. PMC: 2763912. DOI: 10.1016/j.ab.2004.11.026. View

Zimmerman M, Quigley J, ASHE B, Dorn C, Goldfarb R, Troll W . Direct fluorescent assay of urokinase and plasminogen activators of normal and malignant cells: kinetics and inhibitor profiles. Proc Natl Acad Sci U S A. 1978; 75(2):750-3. PMC: 411334. DOI: 10.1073/pnas.75.2.750. View

Achilefu S, Jimenez H, Dorshow R, Bugaj J, Webb E, Wilhelm R . Synthesis, in vitro receptor binding, and in vivo evaluation of fluorescein and carbocyanine peptide-based optical contrast agents. J Med Chem. 2002; 45(10):2003-15. DOI: 10.1021/jm010519l. View

Kato N, Caruso F . Homogeneous, competitive fluorescence quenching immunoassay based on gold nanoparticle/polyelectrolyte coated latex particles. J Phys Chem B. 2006; 109(42):19604-12. DOI: 10.1021/jp052748f. View

Connor E, Mwamuka J, Gole A, Murphy C, Wyatt M . Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small. 2006; 1(3):325-7. DOI: 10.1002/smll.200400093. View

Qian X, Peng X, Ansari D, Yin-Goen Q, Chen G, Shin D . In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol. 2007; 26(1):83-90. DOI: 10.1038/nbt1377. View

Dubertret B, Calame M, Libchaber A . Single-mismatch detection using gold-quenched fluorescent oligonucleotides. Nat Biotechnol. 2001; 19(4):365-70. DOI: 10.1038/86762. View

10.

Duchesne L, Gentili D, Comes-Franchini M, Fernig D . Robust ligand shells for biological applications of gold nanoparticles. Langmuir. 2008; 24(23):13572-80. DOI: 10.1021/la802876u. View

11.

Kang K, Wang J, Jasinski J, Achilefu S . Fluorescence manipulation by gold nanoparticles: from complete quenching to extensive enhancement. J Nanobiotechnology. 2011; 9:16. PMC: 3112388. DOI: 10.1186/1477-3155-9-16. View

12.

Cassidy P, Radda G . Molecular imaging perspectives. J R Soc Interface. 2006; 2(3):133-44. PMC: 1629073. DOI: 10.1098/rsif.2005.0040. View

13.

Kang K, Wang J . Smart dual-mode fluorescent gold nanoparticle agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2014; 6(4):398-409. DOI: 10.1002/wnan.1267. View

14.

Love J, Estroff L, Kriebel J, Nuzzo R, Whitesides G . Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chem Rev. 2005; 105(4):1103-69. DOI: 10.1021/cr0300789. View

15.

Mankoff D . Molecular imaging as a tool for translating breast cancer science. Breast Cancer Res. 2008; 10 Suppl 1:S3. PMC: 2605100. DOI: 10.1186/bcr2126. View

16.

Pakneshan P, Szyf M, Farias-Eisner R, Rabbani S . Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis. J Biol Chem. 2004; 279(30):31735-44. DOI: 10.1074/jbc.M401669200. View

17.

Wang J, Achilefu S, Nantz M, Kang K . Gold nanoparticle-fluorophore complex for conditionally fluorescing signal mediator. Anal Chim Acta. 2011; 695(1-2):96-104. DOI: 10.1016/j.aca.2011.03.058. View

18.

Saha K, Agasti S, Kim C, Li X, Rotello V . Gold nanoparticles in chemical and biological sensing. Chem Rev. 2012; 112(5):2739-79. PMC: 4102386. DOI: 10.1021/cr2001178. View

19.

Acuna G, Bucher M, Stein I, Steinhauer C, Kuzyk A, Holzmeister P . Distance dependence of single-fluorophore quenching by gold nanoparticles studied on DNA origami. ACS Nano. 2012; 6(4):3189-95. DOI: 10.1021/nn2050483. View

20.

Kuhn S, Hakanson U, Rogobete L, Sandoghdar V . Enhancement of single-molecule fluorescence using a gold nanoparticle as an optical nanoantenna. Phys Rev Lett. 2006; 97(1):017402. DOI: 10.1103/PhysRevLett.97.017402. View