Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis

Wang, Chung-Hsin; Kang, Shih‐Tsung; Lee, Ya-Hsuan; Luo, Yun-Ling; Huang, Yu‐Fen; Yeh, Chih‐Kuang

doi:10.1016/j.biomaterials.2011.11.036

Cited by 180 publications

(112 citation statements)

References 35 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Moreover, few studies about ultrasound lipid NBs to carry them for use as molecular probes were reported in ultrasound molecular imaging. 12,13,36 Therefore, this study linked the anti-PSMA aptamer A10-3.2 with ultrasound NBs through the amide reaction, and further established its targeted diagnostic performance in PSMApositive prostate cancer. In this study, light microscopy and LSCM results of the NBs with a particle size of 519.4±74.6 nm showed that NBs could enter tissue spaces through vascular gaps in tumors but could not enter myocardial tissue spaces.…”

mentioning

confidence: 92%

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Fan

Guo

Wang

et al. 2016

IJN

View full text Add to dashboard Cite

In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times ( P >0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different ( P <0.05). In PC-3 xenografts, there were no differences in these four indicators. Fluorescent imaging indicated that targeted nanobubbles had an aggregation ability in C4-2 xenograft tumors. In conclusion, targeted nanobubbles carrying the anti-PSMA A10-3.2 aptamer have a targeted imaging effect in prostate cancer.

show abstract

mentioning

confidence: 92%

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Fan

Guo

Wang

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

“…Aptamer-loaded nanobubbles [45] have been described and show potential for targeting specific cell types. Clearly, targeted microbubbles can be of interest for drug-delivery as well as the amount of drug closely located near the target tissue may become enhanced [46].…”

Section: Targeted Microbubbles For Drug Deliverymentioning

confidence: 99%

Crucial factors and emerging concepts in ultrasound-triggered drug delivery

Geers

Dewitte

Smedt

et al. 2012

Journal of Controlled Release

111

View full text Add to dashboard Cite

“…A10-3.2 aptamers functionalized onto NBs play a crucial role in targeting these particles to a specific subset of prostate cancer cells. 35 We discovered that drug-loaded PLGA passively collected in tumor tissue. Ultrasonic irradiation of the tumor stimulated drug discharge from the PLGA and briefly changed the cell membrane permeability, leading to efficient intracellular uptake of the drug by tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-<em>co</em>-glycolic acid) nanobubbles for ultrasound imaging and therapy of prostate cancer

Wu¹,

Wang²,

Wang³

et al. 2017

IJN

View full text Add to dashboard Cite

In the current study, we synthesized prostate cancer-targeting poly(lactide- co -glycolic acid) (PLGA) nanobubbles (NBs) modified using A10-3.2 aptamers targeted to prostate-specific membrane antigen (PSMA) and encapsulated paclitaxel (PTX). We also investigated their impact on ultrasound (US) imaging and therapy of prostate cancer. PTX-A10-3.2-PLGA NBs were developed using water-in-oil-in-water (water/oil/water) double emulsion and carbodiimide chemistry approaches. Fluorescence imaging together with flow cytometry verified that the PTX-A10-3.2-PLGA NBs were successfully fabricated and could specifically bond to PSMA-positive LNCaP cells. We speculated that, in vivo, the PTX-A10-3.2-PLGA NBs would travel for a long time, efficiently aim at prostate cancer cells, and sustainably release the loaded PTX due to the improved permeability together with the retention impact and US-triggered drug delivery. The results demonstrated that the combination of PTX-A10-3.2-PLGA NBs with low-frequency US achieved high drug release, a low 50% inhibition concentration, and significant cell apoptosis in vitro. For mouse prostate tumor xenografts, the use of PTX-A10-3.2-PLGA NBs along with low-frequency US achieved the highest tumor inhibition rate, prolonging the survival of tumor-bearing nude mice without obvious systemic toxicity. Moreover, LNCaP xenografts in mice were utilized to observe modifications in the parameters of PTX-A10-3.2-PLGA and PTX-PLGA NBs in the contrast mode and the allocation of fluorescence-labeled PTX-A10-3.2-PLGA and PTX-PLGA NBs in live small animals and laser confocal scanning microscopy fluorescence imaging. These results demonstrated that PTX-A10-3.2-PLGA NBs showed high gray-scale intensity and aggregation ability and showed a notable signal intensity in contrast mode as well as aggregation ability in fluorescence imaging. In conclusion, we successfully developed an A10-3.2 aptamer and loaded PTX-PLGA multifunctional theranostic agent for the purpose of obtaining US images of prostate cancer and providing low-frequency US-triggered therapy of prostate cancer that was likely to constitute a strategy for both prostate cancer imaging and chemotherapy.

show abstract

Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis

Cited by 180 publications

References 35 publications

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Crucial factors and emerging concepts in ultrasound-triggered drug delivery

Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-<em>co</em>-glycolic acid) nanobubbles for ultrasound imaging and therapy of prostate cancer

Contact Info

Product

Resources

About