Real-time guidance through fluorescence imaging improves
the surgical
outcomes of tumor resections, reducing the chances of leaving positive
margins behind. As tumors are heterogeneous, it is imperative to interrogate
multiple overexpressed cancer biomarkers with high sensitivity and
specificity to improve surgical outcomes. However, for accurate tumor
delineation and ratiometric detection of tumor biomarkers, current
methods require multiple excitation wavelengths to image multiple
biomarkers, which is impractical in a clinical setting. Here, we have
developed a biomimetic platform comprising near-infrared fluorescent
semiconducting polymer nanoparticles (SPNs) with red blood cell membrane
(RBC) coating, capable of targeting two representative cell-surface
biomarkers (folate, αυβ3 integrins) using a single
excitation wavelength for tumor delineation during surgical interventions.
We evaluate our single excitation ratiometric nanoparticles in in vitro tumor cells, ex vivo tumor-mimicking
phantoms, and in vivo mouse xenograft tumor models.
Favorable biological properties (improved biocompatibility, prolonged
blood circulation, reduced liver uptake) are complemented by superior
spectral features: (i) specific fluorescence enhancement in tumor
regions with high tumor-to-normal tissue (T/NT) ratios in ex vivo samples and (ii) estimation of cell-surface tumor
biomarkers with single wavelength excitation providing insights about
cancer progression (metastases). Our single excitation, dual output
approach has the potential to differentiate between the tumor and
healthy regions and simultaneously provide a qualitative indicator
of cancer progression, thereby guiding surgeons in the operating room
with the resection process.