Smart Nanoparticle-Based Cellular Transfection Tool for Therapeutic Development

Utilizes Light-Responsive Nanoparticles to Load Exosomes with Cargo Molecules Precisely and Efficiently, Maximizing Their Ability as Therapeutics

This smart nanoparticle-based cellular transfection tool utilizes light-responsive nanoparticles to load therapeutic cargo molecules on demand into extracellular vesicles (EVs), or so-called exosomes, for therapeutic development. Developing therapeutic cancer vaccines to modulate immune responses for cancer treatment is of increasing interest. However, such vaccines suffer from weak immunoactivation, low specificity, and side effects. Developing novel cancer vaccines for precise control of anti-tumor immune responses is necessary.

Exosomes are natural carriers secreted by cells, capable of carrying various molecules like nucleic acids, lipids, and proteins. However, delivering therapeutics via exosomes has drawbacks with limited cargo capacity, in turn, leading to inefficient treatment outcomes. Also, precise therapeutic delivery to specific parts of the body becomes a challenge, due to limited targeting mechanisms from exosomes. Therefore, implementing this smart nano-based cellular conventional exosome-based therapy.

Researchers at the University of Florida have developed smart polymeric micelles to use as a nanoparticle-based cellular transfection tool for enhancing site-specific packaging of exosomes with improved cargo loading capacity. The cargo can be packaged into exosomes by the cells at a large scale and is compatible with GMP manufacturing for therapeutic purposes.

Application

Smart polymeric micelles enhance site-specific packaging of therapeutic cargo into exosomes for targeted delivery

Advantages

• Polymeric micelles are engineered to respond to near-UV light, allowing for precise and on-demand release of therapeutic cargo into exosomes during cell culture
• The photo-controlled release strategy avoids complex manipulations without alteration of cell culture, making it suitable for large-scale exosome production during cell culture process and it is compatible with GMP manufacturing
• Micelles are tagged with specific cellular receptor ligands, promoting rapid internalization
• Site-specific packaging and cargo-loading into exosomes, enabling precise delivery to specified tissues or cells

Technology

The functionalized polymeric micelles transport therapeutic peptides into exosome packaging via a photo-controlled and on-demand release of cargo into the cellular endocytic pathway, once the cellular takes place. Then, the cellular compartments packages these therapeutic cargos into exosomes. The photo-controlled release strategy is a straightforward and efficient way for the mass production of exosomes and EVs from cell culture. These smart nanoparticles also tag to specific cellular receptors, facilitating quick uptake and maximizing cellular internalization, resulting in enhanced capacity for loading cargos into exosomes. This nano-transfection technique stimulates cellular synthesis of cargo-loaded exosomes and EVs, satisfying the need for the efficient manufacture of precisely engineered therapeutic exosomes and EVs for improved drug treatment.