Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering


Journal article


Isabella Vasquez, Asma Harun, Robert Posey, Ruhan Reddy, Nikita Gill, Ulrich Bickel, Joshua Tropp, Indrajit Srivastava
ACS Nanosci. Au, ASAP Article, 2025 Oct 6


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APA   Click to copy
Vasquez, I., Harun, A., Posey, R., Reddy, R., Gill, N., Bickel, U., … Srivastava, I. (2025). Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering. ACS Nanosci. Au, ASAP Article. https://doi.org/10.1021/acsnanoscienceau.5c00100


Chicago/Turabian   Click to copy
Vasquez, Isabella, Asma Harun, Robert Posey, Ruhan Reddy, Nikita Gill, Ulrich Bickel, Joshua Tropp, and Indrajit Srivastava. “Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering.” ACS Nanosci. Au ASAP Article (October 6, 2025).


MLA   Click to copy
Vasquez, Isabella, et al. “Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering.” ACS Nanosci. Au, vol. ASAP Article, Oct. 2025, doi:10.1021/acsnanoscienceau.5c00100.


BibTeX   Click to copy

@article{isabella2025a,
  title = {Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering},
  year = {2025},
  month = oct,
  day = {6},
  journal = {ACS Nanosci. Au},
  volume = {ASAP Article},
  doi = {10.1021/acsnanoscienceau.5c00100},
  author = {Vasquez, Isabella and Harun, Asma and Posey, Robert and Reddy, Ruhan and Gill, Nikita and Bickel, Ulrich and Tropp, Joshua and Srivastava, Indrajit},
  month_numeric = {10}
}

Near-infrared (NIR) fluorescence imaging is a powerful, noninvasive tool for cancer diagnosis, enabling real-time, high-resolution visualization of biological systems. While most probes target the first NIR window (NIR-I, 700–900 nm), recent advances focus on the second window (NIR-II, 1000–1700 nm), which offers deeper tissue penetration and reduced interference from scattering and autofluorescence. However, many current NIR-II nanoprobes show suboptimal brightness and limited validation in more human-centric models. Here, we present an orthogonal strategy combining molecular engineering, by modulating the amount and position of thiophene moieties in semiconducting polymers (SPs), with protein nanoengineering to develop ultrabright NIR-II imaging probes optimized for ex vivo bioimaging in large animal models. The molecular tuning amplifies the NIR-II fluorescence brightness while screening endogenous proteins as encapsulating matrices to improve colloidal stability and enable active targeting. Molecular docking identified bovine serum albumin as the effective candidate, and the resulting protein-complexed nanoprobes were characterized for size, colloidal stability under physiological conditions, and optical performance. Imaging performance was evaluated using tumor-mimicking phantoms in porcine lungs, simulating cancer surgery, and injected at clinically relevant concentrations into ovine brains and porcine ovaries for microvascular visualization and tissue discrimination, respectively. In all scenarios, our protein-complexed nanoprobes outperformed the FDA-approved clinical dye indocyanine green in signal-to-background ratios. Initial in vitro assays confirmed their hemocompatibility, biocompatibility, and cellular uptake in ovarian adenocarcinoma cells. This integrated approach offers a promising platform for developing next-generation ultrabright NIR-II nanoprobes with improved brightness and stability, advancing the potential for image-guided surgery and future clinical translation.

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