A multifunctional theranostic contrast agent for ultrasound/near infrared fluorescence imaging-based tumor diagnosis and ultrasound-triggered combined photothermal and gene therapy.

Abstract

PURPOSE:

Encapsulated microbubbles (MBs) have been reported as new theranostic carriers for simultaneous imaging and ultrasound (US)-triggered therapy. Here, we designed a dual-modality US/NIRF contrast agent and extended its applications from image contrast enhancement to combined diagnosis and therapy with US-directed and site-specific targeting.

METHODS:

Gold nanorods (AuNRs) resonant at 880 nm together with the NIR797 dye were first encapsulated in lipid-shelled MBs to construct fluorescent gold microbubbles (NIR797/AuMBs) via thin film hydration and mechanical shaking in the presence of sulfur hexafluoride (SF6) gas. Then, polyethylenimine (PEI)-DNA complexes were electrostatically conjugated onto the surface of the NIR797/AuMBs, forming theranostic encapsulated MBs (PEI-DNA/NIR797/AuMBs). The potential of the PEI-DNA/NIR797/AuMBs for use as a dual-modality contrast enhancement agent was evaluated in vitro and in vivo. The antitumor effect of US/NIR laser irradiation mediating double-fusion suicide gene and photothermal therapy was also investigated using Bel-7402 cells and xenografts.

RESULTS:

The developed theranostic AuMB complexes could not only provide excellent US and NIRF imaging to detect tumors but also serve as an efficient US-triggered carrier for gene delivery and photothermal ablation of tumors in xenografted nude mice. And US + laser exposure group showed a much higher rate of cell inhibition, apoptosis and necrosis as well as a higher Bel-7402 xenograft inhibition rate than the single gene therapy or single exposure (US or laser) group.

CONCLUSIONS:

PEI-DNA/NIR797/AuMBs would be of great value for providing more comprehensive diagnostic information and to guide more accurate and effective synergistic cancer therapy.

STATEMENT OF SIGNIFICANCE:

This is an original paper focusing on developing a dual-modality US/NIRF contrast agent and extended its applications from image contrast enhancement to combined diagnosis and therapy with US-directed and site-specific targeting. The developed theranostic AuMB complexes could not only provide excellent US and NIRF imaging to detect tumors but also serve as an efficient US-triggered carrier for gene delivery and photothermal ablation of tumors in xenografted nude mice. PEI-DNA/NIR797/AuMBs would be of great value for providing more comprehensive diagnostic information and to guide more accurate and effective synergistic cancer therapy.

• Authors: Ling Wang, Hangqing Lu, Qi Gao, Chenyan Yuan, Fengan Ding, Jia Li, Dongsheng Zhang, Xilong Ou
• Journal: Acta biomaterialia (Acta Biomater) Vol. 99 Pg. 373-386 (11 2019) ISSN: 1878-7568 [Electronic] England
• PMID: 31525534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Coloring Agents
• Contrast Media
• Gold
• Polyethyleneimine
• DNA

Topics

• Animals
• Cell Line, Tumor
• Coloring Agents (chemistry)
• Contrast Media (pharmacology)
• DNA (chemistry)
• Female
• Genetic Therapy (methods)
• Gold (chemistry)
• Humans
• Image Processing, Computer-Assisted
• Lasers
• Metal Nanoparticles (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms (diagnostic imaging, therapy)
• Optical Imaging
• Phototherapy (methods)
• Plasmids (metabolism)
• Polyethyleneimine (chemistry)
• Static Electricity
• Theranostic Nanomedicine (methods)
• Transfection
• Ultrasonics
• Ultrasonography