Synthesis of patient-specific nanomaterials

James Lazarovits, Yih Yang Chen, Fayi Song, Wayne Ngo, Anthony J Tavares, Yi-Nan Zhang, Julie Audet, Bo Tang, Qiaochu Lin, Mayra Cruz Tleugabulova, Stefan Wilhelm, Jonathan R Krieger, Thierry Mallevaey, Warren CW Chan

Nano Lett. 2019, 19, 1, 116–123 | DOI:10.1021/acs.nanolett.8b03434

Abstract

Nanoparticles are engineered from materials such as metals, polymers, and different carbon allotropes that do not exist within the body. Exposure to these exogenous compounds raises concerns surrounding toxicity, inflammation, and immune activation. These responses could potentially be mitigated by synthesizing nanoparticles directly from molecules derived from the host. However, efforts to assemble patient-derived macromolecules into structures with the same degree of size and shape tunability as their exogenous counterparts remains a significant challenge. Here we solve this problem by creating a new class of size- and shape-tunable personalized protein nanoparticles (PNP) made entirely from patient-derived proteins. PNPs are built into different sizes and shapes with the same degree of tunability as gold nanoparticles. They are biodegradable and do not activate innate or adaptive immunity following single and repeated administrations in vivo. PNPs can be further modified with specific protein cargos that remain catalytically active even after intracellular delivery in vivo. Finally, we demonstrate that PNPs created from different human patients have unique molecular fingerprints encoded directly into the structure of the nanoparticle. This new class of personalized nanomaterial has the potential to revolutionize how we treat patients and can become an integral component in the diagnostic and therapeutic toolbox.