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Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging.

Fan X, Wang L, Guo Y, Tu Z, Li L, Tong H, Xu Y, Li R, Fang K - PLoS ONE (2015)

Bottom Line: The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence.Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells.Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, China.

ABSTRACT
To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles.

No MeSH data available.


Related in: MedlinePlus

Particle size distributions and in vitro imaging of the Blank NBs and Targeted NBs.A Malvern Zetasizer analyzer was used to examine the particle sizes. Blank NBs (without biotinylated nanobody) had an average diameter of 445.30 ± 32.96 nm (A), whereas Targeted NBs (with biotinylated nanobody) had an average diameter of 487.6 ± 33.55 nm (B). And there is no difference in their in vitro imaging at the same concentrations (C).
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pone.0127419.g003: Particle size distributions and in vitro imaging of the Blank NBs and Targeted NBs.A Malvern Zetasizer analyzer was used to examine the particle sizes. Blank NBs (without biotinylated nanobody) had an average diameter of 445.30 ± 32.96 nm (A), whereas Targeted NBs (with biotinylated nanobody) had an average diameter of 487.6 ± 33.55 nm (B). And there is no difference in their in vitro imaging at the same concentrations (C).

Mentions: The nanobubbles and biotinylated nanobody were conjugated with streptavidin-biotin. A light microscope and Malvern Zetasizer nano ZS90 analyzer were used to study the morphologies and diameters of the Targeted NBs and Blank NBs and revealed that both exhibited regular spherical shapes, and the Targeted NB preparation had an average diameter of 487.60 ± 33.55 nm, whereas the Blank NB preparation had an average diameter of 445.30 ± 32.96 nm; their in vitro imaging effects, namely ultrasound signals, had no differences at the same concentration (P = 0.06, Fig 3). Immunofluorescence later revealed that the targeted NBs emitted green fluorescence signals under the microscope (Fig 4). In contrast, the Blank nanobubbles, which were not labeled with biotinylated nanobody, did not display an apparent fluorescence signal, indicating that the nanobubbles specifically bound the nanobody via biotin-avidin interactions.


Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging.

Fan X, Wang L, Guo Y, Tu Z, Li L, Tong H, Xu Y, Li R, Fang K - PLoS ONE (2015)

Particle size distributions and in vitro imaging of the Blank NBs and Targeted NBs.A Malvern Zetasizer analyzer was used to examine the particle sizes. Blank NBs (without biotinylated nanobody) had an average diameter of 445.30 ± 32.96 nm (A), whereas Targeted NBs (with biotinylated nanobody) had an average diameter of 487.6 ± 33.55 nm (B). And there is no difference in their in vitro imaging at the same concentrations (C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481414&req=5

pone.0127419.g003: Particle size distributions and in vitro imaging of the Blank NBs and Targeted NBs.A Malvern Zetasizer analyzer was used to examine the particle sizes. Blank NBs (without biotinylated nanobody) had an average diameter of 445.30 ± 32.96 nm (A), whereas Targeted NBs (with biotinylated nanobody) had an average diameter of 487.6 ± 33.55 nm (B). And there is no difference in their in vitro imaging at the same concentrations (C).
Mentions: The nanobubbles and biotinylated nanobody were conjugated with streptavidin-biotin. A light microscope and Malvern Zetasizer nano ZS90 analyzer were used to study the morphologies and diameters of the Targeted NBs and Blank NBs and revealed that both exhibited regular spherical shapes, and the Targeted NB preparation had an average diameter of 487.60 ± 33.55 nm, whereas the Blank NB preparation had an average diameter of 445.30 ± 32.96 nm; their in vitro imaging effects, namely ultrasound signals, had no differences at the same concentration (P = 0.06, Fig 3). Immunofluorescence later revealed that the targeted NBs emitted green fluorescence signals under the microscope (Fig 4). In contrast, the Blank nanobubbles, which were not labeled with biotinylated nanobody, did not display an apparent fluorescence signal, indicating that the nanobubbles specifically bound the nanobody via biotin-avidin interactions.

Bottom Line: The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence.Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells.Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, China.

ABSTRACT
To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles.

No MeSH data available.


Related in: MedlinePlus