Direct incorporation of lipophilic nanoparticles into monodisperse perfluorocarbon nanodroplets via solvent dissolution from microfluidic-generated precursor microdroplets.

Multifunctional medical agents based on imaging or therapy nanoparticles (NPs) incorporated into perfluorocarbon (PFC) droplets are promising new agents for cancer detection and treatment. For the first time, monodisperse PFC nanodroplets labeled with NPs have been produced. Lipophilic, as-synthesized, hydrocarbon-stabilized NPs are directly miscibilized into lipophobic PFCs using a removable cosolvent, diethyl ether (DEE), which eliminates the need of the typical time-consuming and expertise-specific NP surface modification steps previously required for NP incorporation into PFCs. This NP-DEE/PFC solution is then used to synthesize monodisperse, micrometer-scale, DEE-infused NP-PFC precursor droplets in water using microfluidics. After precursor microdroplet generation, the DEE cosolvent is removed by dissolution and evaporation, resulting in dramatically smaller, monodisperse, NP-labeled nanodroplets, with final droplet sizes far smaller than the minimum droplet size limit of the microfluidic system, and easily controlled by the amount of DEE mixed in the PFC phase prior to precursor droplet synthesis. Using this technique, unmodified lipophilic quantum dot (QD) NPs were integrated into monodisperse and PFC nanodroplets 165 times smaller in volume than the precursor microdroplets, with dimensions down to 470 nm. The final droplet sizes scaled with the PFC concentrations in the precursor microdroplets, and the QDs remain localized within the droplets after DEE is removed from the system. This method is robust and versatile, and it comprises a platform technology for other unmodified lipophilic NPs and molecules to be incorporated into different types of PFC droplets for the production of new NP-PFC hybrid agents for medical imaging and therapy applications.