Rapid Synthesis of Near Infrared Polymeric Micelles for Real-Time Sentinel Lymph Node Imaging

Abstract

In this manuscript a synthetic methodology for developing sub 20 nm sized polymeric micellar nanoparticles designed for extravascular imaging and therapy is revealed. A simple, one-pot method is followed, which involves a rapid co-self-assembly of an amphiphilic diblock copolymer (PS-b-PAA) and polyoxyethylene (80) sorbitan monooleate in water. Sorbitan monooleate imparts stability to the micelles and helps to drive down the particle size below 20 nm. The particles are incorporated with a water soluble dye ADS832WS, which absorbs in the near infrared range (λ_(ex) = 832 nm) for sensitive detection with optical and photoacoustic imaging techniques. A candidate lipophilic anti-angiogenic therapeutic agent fumagillin was also incorporated with high entrapment (>95%) efficiency. The effectiveness of this theranostic platform for real-time, high-resolution intraoperative photoacoustic imaging for facilitating direct assessment of the sentinel lymph nodes (SLN) in breast cancer staging is demonstrated. The technique offers huge potential providing faster resection of SLN and may minimize complications caused by axillary exploration due to mismarking with dyes or low-resolution imaging techniques. Finally, the biodistribution and organ accumulation of the intravenously and intradermally injected particles are studied in a rodent model by optical imaging. Data suggest that intraveneously injected NIR-polymeric nanoparticles follow a typical bio-distribution clearance path through the reticuloendothelial (RES) system. For the intradermally injected particles, a slower mechanism of clearance is noticed.

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