Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant

Williams, R. T.; Lee, Christopher L.; Galassi, Thomas V.; Harvey, Jackson D.; Leicher, Rachel; Sirenko, Maria; Dorso, M.; Shah, Janki; Olvera, Narciso; Dao, Fanny; Levine, Douglas A.; Heller, Daniel A.

doi:10.1126/sciadv.aaq1090

Cited by 144 publications

(195 citation statements)

References 57 publications

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“…Single-walled carbon nanotubes (SWCNTs) with engineered wrappings 1-4 have recently been developed and utilized in various disparate fields ranging from additives that strengthen material composites [5][6][7][8] to biomedical applications including targeted anti-cancer drug delivery [9][10][11] , nearinfrared (NIR) optical biosensing, [12][13][14] and biological imaging. [15][16][17][18] Of significant interest, SWCNTs exhibit intrinsic photoluminescence (fluorescence) that is photostable, tunable, and sensitive to its local environment.…”

Section: Introductionmentioning

confidence: 99%

DNA Sequence Mediates Apparent Length Distribution in Single-Walled Carbon Nanotubes

Safaee

Gravely

Rocchio

et al. 2018

ACS Appl. Mater. Interfaces

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Single-walled carbon nanotubes (SWCNTs) functionalized with short single-stranded DNA have been extensively studied within the last decade for biomedical applications due to the high dispersion efficiency and intrinsic biocompatibility of DNA as well as the photostable and tunable fluorescence of SWCNTs. Characterization of their physical properties, particularly their length distribution, is of great importance regarding their application as a bioengineered research tool and clinical diagnostic agent. Conventionally, atomic force microscopy (AFM) has been used to quantify the length of DNA-SWCNTs by depositing the hybrids onto an electrostatically charged flat surface. Here, we demonstrate that hybrids of DNA-SWCNTs with different oligomeric DNA sequences ((GT)6 and (GT)30) differentially deposit on the AFM substrate, resulting in significant inaccuracies in the reported length distributions of the parent solutions. Using a solution-based surfactant exchange technique, we placed both samples into a common surfactant wrapping and found identical SWCNT length distributions upon surface deposition. Additionally, by spincoating the surfactant wrapped SWCNTs onto a substrate, thus mitigating effects of electrostatic interactions, we found length distributions that did not depend on DNA sequence but were significantly longer than electrostatic deposition methods, illuminating the inherent bias of the surface deposition method. Quantifying the coverage of DNA molecules on each SWCNT through both absorbance spectroscopy and direct observation, we found that the density of DNA per SWCNT was significantly higher in short (GT)6-SWCNTs (length < 100 nm) compared to long (GT)6-SWCNTs (length > 100 nm). In contrast, we found no dependence of the DNA density on SWCNT length in (GT)30-SWCNT hybrids. Thus, we attribute differences in the observed length distributions of DNA-SWCNTs to variations in electrostatic repulsion induced by sequencedependent DNA density.

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Section: Introductionmentioning

confidence: 99%

DNA Sequence Mediates Apparent Length Distribution in Single-Walled Carbon Nanotubes

Safaee

Gravely

Rocchio

et al. 2018

ACS Appl. Mater. Interfaces

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“…Spectra were acquired from rodents non-invasively in vivo using a custom-built reflectance probe-based spectroscopy system 17, 21, 22 . The excitation was provided by injection of a 730 nm diode laser (Frankfurt) into a bifurcated fiber optic reflection probe bundle (Thorlabs).…”

Section: Methodsmentioning

confidence: 99%

Long-Term In Vivo Biocompatibility of Single-Walled Carbon Nanotubes

Galassi

Antman‐Passig

Yaari

et al. 2019

Preprint

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AbstractOver the past two decades, measurements of carbon nanotube toxicity and biodistribution have yielded a wide range of results. Properties such as nanotube type (single-walled vs. multi-walled), purity, length, aggregation state, and functionalization, as well as route of administration, greatly affect both the biocompatibility and biodistribution of carbon nanotubes. These differences suggest that generalizable conclusions may be elusive and that studies must be material- and application-specific. Here, we assess the short- and long-term biodistribution and biocompatibility of a single-chirality DNA-encapsulated single-walled carbon nanotube complex upon intravenous administration that was previously shown to function as an in-vivo reporter of endolysosomal lipid accumulation. Regarding biodistribution and fate, we found bulk specificity to the liver and >90% signal attenuation by 14 days in mice. Using near-infrared hyperspectral microscopy to measure single nanotubes, we found low-level, long-term persistence in organs such as the heart, liver, lung, kidney, and spleen. Measurements of histology, animal weight, complete blood count, and biomarkers of organ function all suggest short- and long-term biocompatibility. This work suggests that carbon nanotubes can be used as preclinical research tools in-vivo without affecting acute or long-term health.

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“…Covalent attachment could be used for the addition of molecular recognition elements such as antibodies and nanobodies, targeting modalities, and therapeutics. 6,33 We explored this dual-functionality of SWCNT through the attachment of biotin as an affinity pair with avidin ( Fig. 4a).…”

Section: Trz-h-swcnt and Sh-swcnt Covalently-functionalized Swcnt Retmentioning

confidence: 99%

Covalent Surface Modification Effects on Single-Walled Carbon Nanotubes for Multimodal Optical Applications

Chio

Pinals

Goh

et al. 2019

Preprint

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Optical nanoscale technologies often implement covalent or noncovalent strategies for the modification of nanoparticles, whereby both functionalizations can affect the intrinsic fluorescence of nanoparticles. Specifically, single-walled carbon nanotubes (SWCNTs) can enable real-time imaging and cellular delivery, however, the introduction of SWCNT sidewall functionalizations attenuates SWCNT fluorescence. Herein, we leverage recent advances in SWCNT covalent functionalization chemistries that preserve the SWCNT's pristine surface lattice and intrinsic fluorescence, and demonstrate that such covalently-functionalized SWCNT can enable fluorescence-based molecular recognition of neurotransmitter and protein analytes.We show that the covalently-modified SWCNT nanosensor fluorescence signal towards its analyte can be preserved only for certain nanosensors, presumably dependent on the steric hindrance of the SWCNT noncovalent coating. We further demonstrate these SWCNT nanosensors can be functionalized via their covalent handles to self-assemble on passivated microscopy slides and discuss future use of these dual-functionalized SWCNT materials for multiplexed applications.

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Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant

Abstract: Ovarian cancer biomarker detection using a novel nanosensor implant in live mice.

Cited by 144 publications

References 57 publications

DNA Sequence Mediates Apparent Length Distribution in Single-Walled Carbon Nanotubes

DNA Sequence Mediates Apparent Length Distribution in Single-Walled Carbon Nanotubes

Long-Term In Vivo Biocompatibility of Single-Walled Carbon Nanotubes

Covalent Surface Modification Effects on Single-Walled Carbon Nanotubes for Multimodal Optical Applications

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