TY - JOUR
T1 - Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models
AU - Srivastava, Indrajit
AU - Lew, Benjamin
AU - Wang, Yuhan
AU - Blair, Steven
AU - George, Mebin Babu
AU - Hajek, Brianna Scheid
AU - Bangru, Sushant
AU - Pandit, Subhendu
AU - Wang, Ziwen
AU - Ludwig, Jamie
AU - Flatt, Kristen
AU - Gruebele, Martin
AU - Nie, Shuming
AU - Gruev, Viktor
N1 - Funding Information:
S.N. acknowledges the Grainger College of Engineering and the University of Illinois at Urbana–Champaign for institutional support. V.G. thanks the Congressionally Directed Medical Research Program (grant W81XWH-19-1-0299) and the National Science Foundation (grant 2030421). V.G. and S.N. were supported by National Institute of Health (1P01CA254859). M.G. and Y.W. were supported by NSF MCB-2205665. The authors thank Suyue Lyu for her help in running dot-blot studies and polyacrylamide gel electrophoresis experiments, Nickel Liang for data collection in multiplexing study, and Karen Doty for preparing tumor histopathology and immunofluorescent slides. The authors thank Wilson Poon for discussion and feedback on the manuscript. Transmission electron microscopy and dark-field microscopy imaging were carried out in the Materials Research Laboratory Central Research Facilities, University of Illinois.
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/5/9
Y1 - 2023/5/9
N2 - 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.
AB - 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.
KW - biomarker expression
KW - near-infrared fluorescence
KW - red-blood-cell membranes
KW - semiconducting polymer nanoparticles
KW - single wavelength excitation
KW - tumor delineation
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U2 - 10.1021/acsnano.3c00578
DO - 10.1021/acsnano.3c00578
M3 - Article
C2 - 37126072
AN - SCOPUS:85159121414
SN - 1936-0851
VL - 17
SP - 8465
EP - 8482
JO - ACS Nano
JF - ACS Nano
IS - 9
ER -