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Echogenic PEGylated PEI-Loaded Microbubble As Efficient Gene Delivery System.

Chun Liufu¹, Yue Li¹, Jiawei Tu¹

¹Department of Ultrasound Medicine, Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, Experimental Center, The Liwan Hospital of The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, People's Republic of China.

International Journal of Nanomedicine

|December 10, 2019

Summary

This study introduces a novel gene delivery system using ultrasound-stimulated microbubbles (PSP@MB) to effectively target cancer stem cells (CSCs). The system enhances gene delivery to tumors while reducing toxicity, offering a promising therapeutic approach.

Keywords:

PEGylated PEI-loaded microbubble cancer stem cell gene delivery ultrasound

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Area of Science:

Biomedical Engineering
Nanotechnology
Oncology

Background:

Cancer stem cells (CSCs) drive therapeutic resistance and metastasis in ovarian cancer.
Gene delivery offers a potential therapeutic strategy, but tumor heterogeneity poses a challenge.
Ultrasound (US)-stimulated microbubbles (MBs) enable non-invasive targeted gene delivery.

Purpose of the Study:

To demonstrate the utility of poly(ethylene glycol)-SS-polyethylenimine-loaded microbubbles (PSP@MB) as an ultrasound theranostic and redox-responsive agent for gene delivery.
To evaluate the efficacy of PSP@MB in targeting cancer stem cells.

Main Methods:

PSP nanoparticles were conjugated to MBs via biotin-avidin linkage for enhanced gene loading.
Ultrasound exposure significantly increased gene release from PSP@MB complexes.
Morphology, particle size, and zeta potential of PSP@MB were characterized using TEM and DLS.

Main Results:

Ultrasound combined with PSP@MB promoted plasmid cellular uptake and gene transfection efficiency in CSCs.
Reporter genes were successfully delivered to CSCs in vitro and in vivo xenografts.
The system enhanced gene delivery to solid tumors, improving accumulation, extravasation, and penetration while diminishing toxicity to normal tissues.

Conclusions:

The novel PSP@MB and ultrasound-mediated gene delivery system efficiently targets cancer stem cells.
This approach holds promise for improving ovarian cancer therapy by targeting CSCs.