Engineering of Living Cells with Polyphenol-Functionalized Biologically Active Nanocomplexes

Area of Science:

• Biotechnology
• Cell Engineering
• Nanotechnology

Background:

• Augmenting cellular functions without compromising inherent biological properties is a significant challenge.
• Integrating biologically labile domains into cells requires sophisticated approaches.

Purpose of the Study:

• To establish a versatile strategy for assembling biologically active nanocomplexes on cellular surfaces.
• To create a cell-based hybrid system, termed "Cellnex," for enhanced cellular functions and therapeutic applications.

Main Methods:

• Assembly of nanocomplexes (proteins, DNA, mRNA, viral carriers) onto various cell surfaces (erythrocytes, macrophages, NK cells, T cells).
• In vivo evaluation of Erythrocyte_nex for cargo protein delivery to the lungs.
• Biomimetic microfluidic experiments and modeling to elucidate targeting mechanisms.
• In vivo assessment of Macrophage_nex for enhancing anti-PD-L1 checkpoint inhibitor therapy.

Main Results:

• Cellnex strategy successfully engineered diverse cell types for adoptive cell transfers.
• Erythrocyte_nex demonstrated an 11-fold enhancement in lung cargo protein delivery compared to free cargo.
• Macrophage_nex significantly improved the therapeutic efficiency of anti-PD-L1 checkpoint inhibitors in vivo.

Conclusions:

• The Cellnex approach provides a simple, adaptable platform for generating complex cellular systems.
• This strategy holds potential for rapid development of advanced cell-based therapies.
• Cellnex represents a promising advancement in cell engineering for therapeutic delivery and efficacy.