This project will develop a tunable theranostic probe that can support the diagnosis, therapy and therapy guidance in one process in individual specific cells. This will be realized by developing a plasmonic nanobubble (PNB), which is not a particle but an event (transient vapor nanobubble) that is generated on-demand with a short laser pulse around gold nanoparticles targeted to specific cells. Basic biomedical properties of the PNB are related to their optical scattering and mechanical impact and are determined by the PNB diameter that can be tuned starting from 50 nm by varying the energy of the excitation laser pulse. By tuning the size and lifetime of the intracellular PNB, we will realize high-sensitive imaging, controllable delivery, selective cell damage, and optical guidance of the above processes. We will achieve several specific biomedical functions of the PNB: imaging with significantly (100-fold and higher) improved sensitivity and contrast, delivery of molecular loads through controllable localized disrupting of the membrane (of the liposome, of the cell or of the endosome), and cell mechanical (non-thermal) damage with larger PNBs. After determining the mechanisms of biological effects of the PNB, we will combine its different functions into one fast sequence to provide diagnosis, treatment and treatment guidance at the individual cell level. This will be achieved by real-time tuning of the PNB function with several laser pulses and will deliver a cell theranostic process of less than one microsecond duration. Being a stealth, on-demand probe with tunable function, the PNB can be applied to all areas of medicine since the PNB mechanism is universal and can also be employed for detecting and manipulating specific molecules, or for precise microsurgery.

Public Health Relevance

This project is aimed at the development of tunable devices (nanoprobes) called plasmonic nanobubbles that can carry out biomedical diagnosis and therapy in a single fast process at cell level. Such transient bubbles are generated around gold nanoparticles with a short single laser pulse. By tuning dynamically their size we will tune their biological action from a non-invasive sensing, to localized intracellular drug delivery, and to selective elimination of specific cells. Due to their unique tunability of optical and mechanical properties, plasmonic nanobubbles will impact wide areas of research, diagnosis, therapy and micro-surgery by providing the novel universal and efficient nanoprobe.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZGM1-GDB-7 (EU))
Program Officer
Lewis, Catherine D
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Rice University
Schools of Arts and Sciences
United States
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Lukianova-Hleb, Ekaterina Y; Volkov, Alexey N; Lapotko, Dmitri O (2014) Laser pulse duration is critical for the generation of plasmonic nanobubbles. Langmuir 30:7425-34
Park, Mi Seul; Bitto, Eduard; Kim, Kyung Rok et al. (2014) Crystal structure of human protein N-terminal glutamine amidohydrolase, an initial component of the N-end rule pathway. PLoS One 9:e111142
Lukianova-Hleb, Ekaterina Y; Ren, Xiaoyang; Sawant, Rupa R et al. (2014) On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles. Nat Med 20:778-84
Lukianova-Hleb, Ekaterina Y; Campbell, Kelly M; Constantinou, Pamela E et al. (2014) Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria. Proc Natl Acad Sci U S A 111:900-5
Lukianova-Hleb, Ekaterina Y; Lapotko, Dmitri O (2014) Malaria theranostics using hemozoin-generated vapor nanobubbles. Theranostics 4:761-9
Lukianova-Hleb, Ekaterina Y; Volkov, Alexey N; Wu, Xiangwei et al. (2013) Transient enhancement and spectral narrowing of the photothermal effect of plasmonic nanoparticles under pulsed excitation. Adv Mater 25:772-6
Lapotko, Dmitri O (2013) Nanophotonics and theranostics: will light do the magic? Theranostics 3:138-40
Lukianova-Hleb, Ekaterina Y; Sassaroli, Elisabetta; Jones, Alicia et al. (2012) Transient photothermal spectra of plasmonic nanobubbles. Langmuir 28:4858-66
Lukianova-Hleb, Ekaterina Y; Ren, Xiaoyang; Constantinou, Pamela E et al. (2012) Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems. PLoS One 7:e34537
Lukianova-Hleb, Ekaterina Y; Wagner, Daniel S; Brenner, Malcolm K et al. (2012) Cell-specific transmembrane injection of molecular cargo with gold nanoparticle-generated transient plasmonic nanobubbles. Biomaterials 33:5441-50

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