Preparation of near-infrared-labeled targeted contrast agents for clinical translation

2011 ◽  
Author(s):  
D. Michael Olive
2020 ◽  
Vol 12 (542) ◽  
pp. eaay0712 ◽  
Author(s):  
Lei G. Wang ◽  
Connor W. Barth ◽  
Catherine H. Kitts ◽  
Mubark D. Mebrat ◽  
Antonio R. Montaño ◽  
...  

Nerve-binding fluorophores with near-infrared (NIR; 650 to 900 nm) emission could reduce iatrogenic nerve injury rates by providing surgeons precise, real-time visualization of the peripheral nervous system. Unfortunately, current systemically administered nerve contrast agents predominantly emit at visible wavelengths and show nonspecific uptake in surrounding tissues such as adipose, muscle, and facia, thus limiting detection to surgically exposed surface-level nerves. Here, a focused NIR fluorophore library was synthesized and screened through multi-tiered optical and pharmacological assays to identify nerve-binding fluorophore candidates for clinical translation. NIR nerve probes enabled micrometer-scale nerve visualization at the greatest reported tissue depths (~2 to 3 mm), a feat unachievable with previous visibly emissive contrast agents. Laparoscopic fluorescent surgical navigation delineated deep lumbar and iliac nerves in swine, most of which were invisible in conventional white-light endoscopy. Critically, NIR oxazines generated contrast against all key surgical tissue classes (muscle, adipose, vasculature, and fascia) with nerve signal-to-background ratios ranging from ~2 (2- to 3-mm depth) to 25 (exposed nerve). Clinical translation of NIR nerve-specific agents will substantially reduce comorbidities associated with surgical nerve damage.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 756
Author(s):  
Manoj Kumar Mahata ◽  
Ranjit De ◽  
Kang Taek Lee

Due to the unique properties of lanthanide-doped upconverting nanoparticles (UCNP) under near-infrared (NIR) light, the last decade has shown a sharp progress in their biomedicine applications. Advances in the techniques for polymer, dye, and bio-molecule conjugation on the surface of the nanoparticles has further expanded their dynamic opportunities for optogenetics, oncotherapy and bioimaging. In this account, considering the primary benefits such as the absence of photobleaching, photoblinking, and autofluorescence of UCNPs not only facilitate the construction of accurate, sensitive and multifunctional nanoprobes, but also improve therapeutic and diagnostic results. We introduce, with the basic knowledge of upconversion, unique properties of UCNPs and the mechanisms involved in photon upconversion and discuss how UCNPs can be implemented in biological practices. In this focused review, we categorize the applications of UCNP-based various strategies into the following domains: neuromodulation, immunotherapy, drug delivery, photodynamic and photothermal therapy, bioimaging and biosensing. Herein, we also discuss the current emerging bioapplications with cutting edge nano-/biointerfacing of UCNPs. Finally, this review provides concluding remarks on future opportunities and challenges on clinical translation of UCNPs-based nanotechnology research.


ACS Nano ◽  
2018 ◽  
Vol 12 (12) ◽  
pp. 11986-11994 ◽  
Author(s):  
Peng Si ◽  
Edwin Yuan ◽  
Orly Liba ◽  
Yonatan Winetraub ◽  
Siavash Yousefi ◽  
...  

2018 ◽  
Author(s):  
Wei Chen ◽  
ChiAn Cheng ◽  
Emily Cosco ◽  
Shyam Ramakrishnan ◽  
Jakob Lingg ◽  
...  

Tissue is translucent to shortwave infrared (SWIR) light, rendering optical imaging superior in this region. However, the widespread use of optical SWIR imaging has been limited, in part, by the lack of bright, biocompatible contrast agents that absorb and emit light above 1000 nm. J-aggregation offers a means to transform stable, near-infrared (NIR) fluorophores into red-shifted SWIR contrast agents. Here we demonstrate that hollow mesoporous silica nanoparticles (HMSNs) can template the J-aggregation of NIR fluorophore IR-140 to result in nanomaterials that absorb and emit SWIR light. The J-aggregates inside PEGylated HMSNs are stable for multiple weeks in buffer and enable high resolution imaging <i>in vivo</i>with 980 nm excitation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Kenneth S. Hettie

Thrombosis within the vasculature arises when pathological factors compromise normal hemostasis. On doing so, arterial thrombosis (AT) and venous thrombosis (VT) can lead to life-threatening cardio-cerebrovascular complications. Unfortunately, the therapeutic window following the onset of AT and VT is insufficient for effective treatment. As such, acute AT is the leading cause of heart attacks and constitutes ∼80% of stroke incidences, while acute VT can lead to fatal therapy complications. Early lesion detection, their accurate identification, and the subsequent appropriate treatment of thrombi can reduce the risk of thrombosis as well as its sequelae. As the success rate of therapy of fresh thrombi is higher than that of old thrombi, detection of the former and accurate identification of lesions as thrombi are of paramount importance. Magnetic resonance imaging, x-ray computed tomography (CT), and ultrasound (US) are the conventional non-invasive imaging modalities used for the detection and identification of AT and VT, but these modalities have the drawback of providing only image-delayed indirect visualization of only late stages of thrombi development. To overcome such limitations, near-infrared (NIR, ca. 700–1,700 nm) fluorescence (NIRF) imaging has been implemented due to its capability of providing non-invasive real-time direct visualization of biological structures and processes. Contrast agents designed for providing real-time direct or indirect visualization of thrombi using NIRF imaging primarily provide peak NIR-I fluorescence emission (ca. 700–1,000 nm), which affords limited tissue penetration depth and suboptimal spatiotemporal resolution. To facilitate the enhancement of the visualization of thrombosis via providing detection of smaller, fresh, and/or deep-seated thrombi in real time, the development of contrast agents with peak NIR-II fluorescence emission (ca. 1000–1,700 nm) has been recently underway. Currently, however, most contrast agents that provide peak NIR-II fluorescence emissions that are purportedly capable of providing direct visualization of thrombi or their resultant occlusions actually afford only the indirect visualization of such because they only provide for the (i) measuring of the surrounding vascular blood flow and/or (ii) simple tracing of the vasculature. These contrast agents do not target thrombi or occlusions. As such, this mini review summarizes the extremely limited number of targeting contrast agents with peak NIR-II fluorescence emission developed for non-invasive real-time direct visualization of thrombosis that have been recently reported.


2016 ◽  
Vol 4 (33) ◽  
pp. 5560-5566 ◽  
Author(s):  
Lesan Yan ◽  
Huiquan Wang ◽  
Anqi Zhang ◽  
Calvin Zhao ◽  
Yongping Chen ◽  
...  

The IR780@NPs exhibited excellent characteristics for in vivo imaging with a long circulation time and high retention in tumor and sentinel lymph node.


Inorganics ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 129
Author(s):  
Sara Lacerda

Molecular magnetic resonance imaging (MRI) provides information non-invasively at cellular and molecular levels, for both early diagnosis and monitoring therapeutic follow-up. This imaging technique requires the development of a new class of contrast agents, which signal changes (typically becomes enhanced) when in presence of the cellular or molecular process to be evaluated. Even if molecular MRI has had a prominent role in the advances in medicine over the past two decades, the large majority of the developed probes to date are still in preclinical level, or eventually in phase I or II clinical trials. The development of novel imaging probes is an emergent active research domain. This review focuses on gadolinium-based specific-targeted contrast agents, providing rational design considerations and examples of the strategies recently reported in the literature.


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