Layer-by-layer assembled fluorescent probes in the second near-infrared window for systemic delivery and detection of ovarian cancer

Abstract

Fluorescence imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) features deep tissue penetration, reduced tissue scattering, and diminishing tissue autofluorescence. Here, NIR-II fluorescent probes, including down-conversion nanoparticles, quantum dots, single-walled carbon nanotubes, and organic dyes, are constructed into biocompatible nanoparticles using the layer-bylayer (LbL) platform due to its modular and versatile nature. The LbL platform has previously been demonstrated to enable incorporation of diagnostic agents, drugs, and nucleic acids such as siRNA while providing enhanced blood plasma half-life and tumor targeting. This work carries out head-to-head comparisons of currently available NIR-II probes with identical LbL coatings with regard to their biodistribution, pharmacokinetics, and toxicities. Overall, rare-earth-based down-conversion nanoparticles demonstrate optimal biological and optical performance and are evaluated as a diagnostic probe for high-grade serous ovarian cancer, typically diagnosed at late stage. Successful detection of orthotopic ovarian tumors is achieved by in vivo NIR-II imaging and confirmed by ex vivo microscopic imaging. Collectively, these results indicate that LbL-based NIR-II probes can serve as a promising theranostic platform to effectively and noninvasively monitor the progression and treatment of serous ovarian cancer.second near-infrared window | layer by layer | systemic comparison | ovarian tumor detection | deep penetration

Single-walled carbon nanotubes as optical probes for bio-sensing and imaging

“…31,32,50,88 Compared to normal cells, cancerous cells usually have greater permeability and retention effect. For tumor type specific imaging, several strategies were developed to conjugate recognition elements to SWCNTs including crosslinking to lipids functionalization layer 31,46,63,89 , modifying M13 virus stabilized nanotubes 88 , or through layer-bylayer deposition 90 . 8A).…”

Molecular imaging of biological systems with a clickable dye in the broad 800- to 1,700-nm near-infrared window

“…In vitro molecular imaging of cells and tissues in 2D or 3D space (15)(16)(17) could strongly benefit from the broader spectral imaging window extending into NIR-II, adding more colors and increased multiplexing capability, accompanied by the advantages of increased penetration depth and reduced tissue endogenous autofluorescence levels afforded by molecular NIR-II probes (12,18,19). The increased photon penetration depth allows for visualization of deeper physiological structures, opening the possibility of layer-by-layer fluorescence imaging for 3D molecular imaging using simple one-photon techniques (9,20,21). Furthermore, the low NIR-II tissue autofluorescence that eventually could reach near-zero levels in the NIR-IIb (1,500-1,700 nm) window could facilitate a marked increase in fluorescent probe signal-to-background ratios and imaging specificity for fluorescent probes (22)(23)(24).…”

Over-1000 nm near-infrared fluorescent biodegradable polymer nanoparticles for deep tissue in vivo imaging in the second biological window

“…[12][13][14] Because low-molecular-weight compounds can be cleared from the blood by a renal clearance mechanism, low-molecular-weight dyes are attractive candidates for human clinical applications. Several kinds of laser dyes, such as IR-26, IR-1048 and IR-1061, are known to show OTN-NIR emission.…”

“…12,13 In these studies, dyes are loaded into the hydrophobic layer of polymer nanoparticles, thus allowing OTN-NIR emission in an aqueous environment. However, synthesis of these materials involves the use of several different kinds of polymer materials, a stepwise mixing process and/or formation of a layer-by-layer structure.…”

“…However, synthesis of these materials involves the use of several different kinds of polymer materials, a stepwise mixing process and/or formation of a layer-by-layer structure. 12,13 Therefore, sample preparation requires a complicated procedure and a long preparation time. Furthermore, successful blood circulation of nanoparticles requires an adequate particle size.…”