While nanoparticles (NPs) show promise as vehicles for targeted drug delivery, rapid clearance from circulation post-intravenous (IV) injection hinders clinical translatability: less than 1% of IV-injected NPs reach destined tumor sites in diseased tissue. By selectively hitchhiking blood components in whole blood after IV injection, it is possible to optimally deliver dramatically larger doses of nanoparticles to only targeted tissue sites, eliminating off target-effects from accumulation in the liver and spleen.
Ionic liquids (ILs) are liquid salts under 100^○C composed of bulky asymmetric cations and anions. We have shown that a choline carboxylic acid-based ILs are able to coat the surface of poly(lactic-co-glycolic acid) [50:50] (PLGA) nanoparticles (NPs). When mixed with blood, the IL-coated nanoparticles selectively attach to membranes of blood components. To understand and engineer this mechanism of hitchhiking in whole blood, we screened 60+ choline-coordinated carboxylic acid anions, varying molar ionic ratio, alkyl chain saturation, and functionalization. These ILs were coated on surfaces of PLGA NPs and the structural relationship between the anion and affinity towards biological membranes were studied ex-vivo in whole BALB/c mouse blood. The degree of hitchhiking was measured both qualitatively (fluorescence activated cell sorting (FACS)) and quantitatively (fluorescent plate reader). We thus present IL candidates that show spontaneous selective affinity towards hitchhiking lymphocytes, monocytes, granulocytes, platelets, and red blood cells in whole blood.

Choline carboxylic acid-based ionic liquids can coat polymeric nanoparticles (cryo-EM image) to enable targeted cellular hitchhiking. Pictured is a red blood cell.

Eden Tanner

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