Abstract The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high spatial resolution, low background signal, and deep tissue penetration properties, but NIR‐II dyes with adequate in vivo performance and safety profiles are scarce. A novel NIR‐II fluorophore, XW‐03‐66, with a fluorescence quantum yield (QY) of 6.0% in aqueous media is reported. XW‐03‐66 self‐assembles into nanoparticles (≈80 nm) and has a systemic circulation half‐life ( t 1/2 ) of 11.3 h. In mouse models of human papillomavirus (HPV)+ and HPV‐ OSCC, XW‐03‐66 outperformed indocyanine green (ICG), a clinically available NIR dye, and enabled intraoperative NIR‐II image‐guided resection of the tumor and adjacent draining lymph node with negative margins. In vitro and in vivo toxicity assessments revealed minimal safety concerns for in vivo applications.
more »
« less
This content will become publicly available on August 1, 2024
NIR-II Nanoprobes: A Review of Components-Based Approaches to Next-Generation Bioimaging Probes
Fluorescence and photoacoustic imaging techniques offer valuable insights into cell- and tissue-level processes. However, these optical imaging modalities are limited by scattering and absorption in tissue, resulting in the low-depth penetration of imaging. Contrast-enhanced imaging in the near-infrared window improves imaging penetration by taking advantage of reduced autofluorescence and scattering effects. Current contrast agents for fluorescence and photoacoustic imaging face several limitations from photostability and targeting specificity, highlighting the need for a novel imaging probe development. This review covers a broad range of near-infrared fluorescent and photoacoustic contrast agents, including organic dyes, polymers, and metallic nanostructures, focusing on their optical properties and applications in cellular and animal imaging. Similarly, we explore encapsulation and functionalization technologies toward building targeted, nanoscale imaging probes. Bioimaging applications such as angiography, tumor imaging, and the tracking of specific cell types are discussed. This review sheds light on recent advancements in fluorescent and photoacoustic nanoprobes in the near-infrared window. It serves as a valuable resource for researchers working in fields of biomedical imaging and nanotechnology, facilitating the development of innovative nanoprobes for improved diagnostic approaches in preclinical healthcare.
more »
« less
- Award ID(s):
- 2128821
- NSF-PAR ID:
- 10451708
- Date Published:
- Journal Name:
- Bioengineering
- Volume:
- 10
- Issue:
- 8
- ISSN:
- 2306-5354
- Page Range / eLocation ID:
- 954
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
more » « less
Abstract Photoswitchable fluorescent proteins (PFPs) that can change fluorescence color upon excitation have revolutionized many applications of light such as tracking protein movement, super-resolution imaging, identification of circulating cells, and optical data storage. Nevertheless, the relatively weak fluorescence of PFPs limits their applications in biomedical imaging due to strong tissue autofluorecence background. Conversely, plasmonic nanolasers, also called spasers, have demonstrated potential to generate super-bright stimulated emissions even inside single cells. Nevertheless, the development of photoswitchable spasers that can shift their stimulated emission color in response to light is challenging. Here, we introduce the novel concept of spasers using a PFP layer as the active medium surrounding a plasmonic core. The proof of principle was demonstrated by synthesizing a multilayer nanostructure on the surface of a spherical gold core, with a non-absorbing thin polymer shell and the PFP Dendra2 dispersed in the matrix of a biodegradable polymer. We have demonstrated photoswitching of spontaneous and stimulated emission in these spasers below and above the spasing threshold, respectively, at different spectral ranges. The plasmonic core of the spasers serves also as a photothermal (and potentially photoacoustic) contrast agent, allowing for photothermal imaging of the spasers. These results suggest that multimodal photoswitchable spasers could extend the traditional applications of spasers and PFPs in laser spectroscopy, multicolor cytometry, and theranostics with the potential to track, identify, and kill abnormal cells in circulation.
-
more » « less
Optical methods of biomedical tomographic imaging are of considerable interest due to their non-invasive nature and sensitivity to physiologically important markers. Similarly to other imaging modalities, optical methods can be enhanced by utilizing extrinsic contrast agents. Typically, these are fluorescent molecules, which can aggregate in regions of interest due to various mechanisms. In the current approaches to imaging, the intrinsic (related to the tissue) and extrinsic (related to the contrast agent) optical parameters are determined separately. This can result in errors, in particular, due to using simplified heuristic models for the spectral dependence of the optical parameters. Recently, we have developed the theory of non-reciprocal broken-ray tomography (NRBRT) for fluorescence imaging of weakly scattering systems. NRBRT enables simultaneous reconstruction of the fluorophore concentration as well as of the intrinsic optical attenuation coefficient at both the excitation and the emission wavelengths. Importantly, no assumption about the spectral dependence of the tissue optical properties is made in NRBRT. In this study, we perform numerical validation of NRBRT under realistic conditions using the Monte Carlo method to generate forward data. We demonstrate that NRBRT can be used for tomographic imaging of samples of up to four scattering lengths in size. The effects of physical characteristics of the detectors such as the area and the acceptance angle are also investigated.
-
more » « less
Abstract Surfactant‐stripped micelles are formed from a commercially available cyanine fluoroalkylphosphate (CyFaP) salt dye and used for high contrast photoacoustic imaging (PAI) in the second near‐infrared window (NIR‐II). The co‐loading of Coenzyme Q10 into surfactant‐stripped CyFaP (ss‐CyFaP) micelles improves yield, storage stability, and results in a peak absorption wavelength in the NIR‐II window close to the 1064 nm output of Nd‐YAG lasers used for PAI. Aqueous ss‐CyFaP dispersions exhibit intense NIR‐II optical absorption, calculated to be greater than 500 at 1064 nm. ss‐CyFaP is detected through 12 cm of chicken breast tissue with PAI. In preclinical animal models, ss‐CyFaP is visualized in draining lymph nodes of rats through 3.1 cm of overlaid chicken breast tissue. Following intravenous administration, ss‐CyFaP accumulates in neoplastic tissues of mice and rats bearing orthotopic mammary tumors without observation of acute toxic side effects. ss‐CyFaP is imaged through whole compressed human breasts in three female volunteers at depths of 2.6–5.1 cm. Taken together, these data show that ss‐CyFaP is an accessible contrast agent for deep tissue PAI in the NIR‐II window.
-
more » « less
Abstract The photoacoustic effect—the generation of a sound wave upon absorption of light by a sample—was developed over the past decades into photoacoustic imaging (
PAI ), and related technologies. These imaging modalities combine the advantages of optical imaging techniques (high resolution) with those of ultrasonic imaging (deep imaging depth). The light absorption by a tissue sample can be because of endogenous absorbers (such as hemoglobin or melanins). Alternatively—and most advantageously—is the use of exogenous dyes as contrast agents. Borg and Rochford present in thisJournal (Photochem. Photobiol ., 2018,https://doi.org/10.1111/php.12967 ) a comprehensive review of molecular dyes reported as contrast agents forPAI , referred to as molecular photoacoustic contrast agents (MPAC s). Highlighted here isPAI as a most promising biomedical imaging modality and the importance of the rational development of novel, high‐efficiencyMPAC s, an endeavor for which Borg and Rochford provided an excellent resource for novices and experts in the field, and anyone else interested in bioimaging or the interaction of light with chromophores.
