Gold nanocages with dual modality for image-guided therapeutics

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• MicroRNAs play a critical role in cancer development and progression.
• The influence of microRNA delivery system size on cellular uptake, biodistribution, and therapeutic efficacy requires further investigation.
• Developing effective non-viral vectors for microRNA delivery is crucial for advancing cancer therapy.

Purpose of the Study:

• To construct and evaluate differently-sized microRNA delivery systems for hepatocellular carcinoma (HCC) therapy.
• To investigate the impact of particle size on the cellular uptake and biodistribution of microRNA delivery systems.
• To assess the therapeutic potential of optimized microRNA delivery systems in HCC models.

Main Methods:

• Fabrication of size-tunable, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs) loaded with miR-26a.
• In vitro evaluation of cellular uptake in BEL-7402 cell lines.
• In vivo assessment of biodistribution and therapeutic efficacy in subcutaneous and orthotopic HCC mouse models.
• Optical monitoring using fluorescence and photoacoustic tomography imaging.

Main Results:

• Particle size significantly affects cellular uptake and biodistribution, with 30 nm PPHAuNCs-TNCs demonstrating optimal performance.
• PPHAuNCs-30-TNCs exhibited enhanced accumulation in the liver of orthotopic HCC mouse models compared to normal mice.
• PPHAuNCs-30-TNCs significantly inhibited tumor growth in orthotopic HCC models under near-infrared irradiation.

Conclusions:

• Particle size is a critical factor in designing efficient microRNA delivery systems for cancer therapy.
• The optimized 30 nm PPHAuNCs-TNCs show significant potential for hepatocellular carcinoma diagnosis and treatment.
• This study provides valuable insights for the development of novel non-viral microRNA vectors for oncological applications.