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. 2024 May 22:19:4651-4665.
doi: 10.2147/IJN.S462917. eCollection 2024.

Construction of a Tumor-Targeting Nanobubble with Multiple Scattering Interfaces and its Enhancement of Ultrasound Imaging

Zhengjun Ma  1 , Yanmei Zhang  1 , Yupu Zhu  2 , Minxuan Cui  2 , Yutao Liu  2 , Yun-You Duan  1 , Li Fan  2 , Li Zhang  1
Affiliations

Construction of a Tumor-Targeting Nanobubble with Multiple Scattering Interfaces and its Enhancement of Ultrasound Imaging

Zhengjun Ma et al. Int J Nanomedicine. .

Abstract

Introduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection.

Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo.

Results: The results show that IR783-SiO2NPs@NB had a "donut-type" composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability.

Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.

Keywords: CEUS; SiO2 NPs; nanobubbles; scattering cross-section; ultrasound contrast agents.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Characteristics and morphology of SiO2 NPs.
Figure 2
Figure 2
Characteristics and morphology of IR783-SiO2NPs@NB.
Figure 3
Figure 3
The diameter (A) and the concentration (B) of IR783-SiO2NPs@NB changes over time at 25°C. (C) The cytotoxicity for various concentrations of IR783-SiO2NPs@NB determined using the CCK-8 assay.
Figure 4
Figure 4
The tumor specific binding efficiency of NBs was evaluated by co-incubation with VX2 cells in vitro.
Figure 5
Figure 5
Evaluation of echogenicity of IR783-SiO2NPs@NB in vitro.
Figure 6
Figure 6
Evaluation of the CEUS imaging capacity of IR783-SiO2NPs@NB in vivo.
Figure 7
Figure 7
(A) The in vivo tumor tissue accumulation of IR783-SiO2NPs@NB (up) and saline (down) at 1 hour evaluated by NIRF imaging. (B) Ex vivo fluorescence imaging of the lung, spleen, kidney, heart, liver, and tumor at different time points after IR783-SiO2NPs@NB injection. (C) H&E staining was conducted on heart, kidney, liver, spleen, and lung sections of nude mice injected with IR783-SiO2NPs@NB (up) and saline (down).
See this image and copyright information in PMC

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