Modified tumor uptake and biodistribution of nanoparticles coated with small extracellular vesicle membranes derived from distinct tumor cell lines

TL;DR

Coating nanoparticles with exosome membranes from tumor cells improves their targeting and heating effects in tumors, but also affects their distribution in the body.

Contribution

The study demonstrates how exosome-coated nanoparticles enhance tumor targeting and thermal therapy efficacy while altering biodistribution.

Findings

Exosome-coated nanoparticles are taken up more rapidly by tumor cells and accumulate in multivesicular bodies.

Exosome coating improves immunoevasion and organ accumulation but limits tumor extravasation.

Magnetic heating with exosome-coated particles significantly reduces tumor cell viability compared to uncoated particles.

Abstract

Targeting tumors with nanoparticles can significantly improve the anti-tumor effect of thermal treatments while sparing normal tissue from nonspecific effects. The surface coating is essential to driving the biological fate of nanomaterials. Exosomes, a type of long-circulating secreted vesicle, are capable of specific cell targeting and present a variety of molecules on the surface.

Differences among physiochemical properties and protein expression of the exosome isolates were quantified based on the origin of the exosomes. Extrusion through polycarbonate membranes was used to coat nanoparticles with these membranes. TEM was used to visualize cell uptake in vitro, and biodistribution was quantified using ICP-MS following intravenous injection in mice bearing 4T1 breast tumors. Alternating magnetic field was used to heat cells after incubation with nanoparticles in vitro.

The exosome coating promoted particle immunoevasion and accumulation in different organs, though it limited extravasation within the tumor as well, independent of the source cell line. TEM of individual tumor cells showed that particles with exosome coating are taken up more rapidly than uncoated particles and these particles accumulate in multivesicular bodies. Particles were incubated in vitro with 4T1 tumor cells and heat treated. The exosome-coated particles combined with magnetic heating led to a greater decrease in tumor cell viability than with uncoated particles.

Significant changes in biodistribution, cellular uptake, and heating induced by alternating magnetic field were observed with these formulations. Studies are ongoing to identify the proteins needed to maximize tumor accumulation and efficacy of thermal therapy.

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