期刊
ACS NANO
卷 7, 期 12, 页码 10671-10680出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn403370e
关键词
microfluidics; nanoparticle; nanomedicine; rapid synthesis; mixing
类别
资金
- Koch-Prostate Cancer Foundation Award in Nanotherapeutics
- National Cancer Institute (NCI) Center of Cancer Nanotechnology Excellence at MIT-Harvard [U54-CA151884]
- National Heart, Lung, and Blood Institute (NHLBI) Programs of Excellence in Nanotechnology [HHSN268201000045C]
- National Science Foundation (NSF)
- NDSEG graduate research fellowship
- Center of Cancer Nanotechnology Excellence graduate research fellowship [5 U54 CA151884-02]
Taking a nanoparticle (NP) from discovery to clinical translation has been slow compared to small molecules, in part by the lack of systems that enable their precise engineering and rapid optimization. In this work we have developed a microfluidic platform for the rapid, combinatorial synthesis and optimization of NPs. The system takes in a number of NP precursors from which a library of NPs with varying size, surface charge, target ligand density, and drug load is produced in a reproducible manner. We rapidly synthesized 45 different formulations of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) NPs of different size and surface composition and screened and ranked the NPs for their ability to evade macrophage uptake in Comparison of the results to pharmacokinetic studies in vivo in mice revealed a correlation between in vitro screen and in vivo Next, we selected NP synthesis parameters that resulted in longer blood half-life and used the microfluidic platform to targeted NPs with varying targeting ligand density (using a model targeting ligand against cancer cells). We screened NPs in vitro prostate cancer cells as well as macrophages, identifying one formulation that exhibited high uptake by cancer cells yet similar uptake compared to nontargeted NPs. In vivo, the selected targeted NPs showed a 3.5-fold increase in tumor accumulation in mice compared to nontargeted NPs. The developed microfluidic platform in this work represents a tool that could potentially accelerate the discovery and clinical translation of NPs.
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