Flash NanoPrecipitation enables the production of nanoparticle drug cocktails and multivalent targeted nanoparticles for imaging and drug delivery

R.K. Prud’homme
Princeton University, US

Keywords: nanoparticle, nano carrier, fluorescence, MRI, up converting phosphor, multimodal

Summary:

We have developed a block-copolymer-directed, kinetically-controlled self-assembly process called Flash NanoPrecipitation (FNP) to produce 50-400 nm nanoparticles. The process involves controlling micromixing to effect supersaturations as high as 10,000 in 1.5 ms, and then controlling nucleation and growth rates to match block copolymer assembly rates. The rapid assembly enables the encapsulation of multiple drugs and imaging agents into the same nanoparticle, and the production of multivalent targeted nanoparticles. The flexibility of the assembly process enables the preparation of imaging nanoparticles based on various modalities: 1) Fluorescent imaging of new hydrophobic long wavelength dyes that have exceptional photostability and are non-quenching, which enables high fluorophore loading. They reside in the core of the nanoparticle and are therefore unaffected by the biological environment, and do not contribute to surface recognition artifacts that may affect most surface-functionalized fluorphors. 2) MRI imaging where the co-encapsulation of SPIO magnetic nanoparticles and therapeutic agents enables into the same nanocarrier enables MRI contrast equivalent to commercial MRI agents, which can not simultaneously delivery therapeutics. 3) Up Converting Phosphors (UCPs) that enable both deep optical penetration of tissue and co-delivery of agents for photodynamic therapy.