Editors' ChoiceNanomedicine

Finding the Proverbial Needle

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Science Translational Medicine  04 Dec 2013:
Vol. 5, Issue 214, pp. 214ec201
DOI: 10.1126/scitranslmed.3008076

Multifunctional nanoparticles can do many things at once, from targeting tumors to releasing drugs to staving off immune responses. The challenge is to identify optimal combinations of particle properties that enhance therapeutic outcomes. To address this issue, Valencia et al. created a microfluidic system for rapid synthesis and screening of nanoparticles with properties that ensure uptake by cancer cells while limiting clearance by the immune system.

A nanoparticle’s function is to evade the immune system, target tumor cells, and deliver therapeutics—all of which is largely determined by properties such as size, surface charge, ligand density, and drug content. The authors engineered a microfluidic device that mixes various nanoparticle precursors at controllable ratios and then outputs tens of different formulations of polymeric particles with custom-made properties. Valencia and coauthors initially used the device to make nanoparticles with varying weights and densities of poly(ethylene glycol) (PEG) because PEG is known to avoid an immune response. Small (25 to 30 nm) nanoparticles along with high PEG content and longer PEG molecules (10 kD) mostly evaded macrophage uptake in vitro, which was confirmed in a mouse model with extended circulation time. The authors next investigated the effect of different targeting ligand densities on particle uptake by macrophages as well as a prostate cancer cell line. Nanoparticles with less than 200 ligands per particle exhibited significant uptake by the cancer cells with minimal uptake by the macrophages both in vitro and in vivo in a human prostate tumor model, as compared with nanoparticles without a targeting ligand.

Overall, this high-throughput approach offers an important step toward rapid generation and screening of nanoparticles with custom properties. However, before the platform is clinic-ready, a recipe book of precursor concentrations and flow rates should be compiled for reproducibly obtaining a library of nanoparticles with validated property combinations.

P. M. Valencia et al., Microfluidic platform for combinatorial synthesis and optimization of targeted nanoparticles for cancer therapy. ACS Nano, published online 11 November 2013 (10.1021/nn403370e). [Abstract]

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