Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models

Indrajit Srivastava, Benjamin Lew, Yuhan Wang, Steven Blair, Mebin Babu George, Brianna Scheid Hajek, Sushant Bangru, Subhendu Pandit, Ziwen Wang, Jamie Ludwig, Kristen Flatt, Martin Gruebele, Shuming Nie, Viktor Gruev

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8465–8482
Number of pages18
JournalACS Nano
Volume17
Issue number9
DOIs
StatePublished - May 9 2023

Keywords

  • biomarker expression
  • near-infrared fluorescence
  • red-blood-cell membranes
  • semiconducting polymer nanoparticles
  • single wavelength excitation
  • tumor delineation

ASJC Scopus subject areas

  • General Engineering
  • General Materials Science
  • General Physics and Astronomy

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