Ryan M. Williams
Memorial Sloan Kettering Cancer Center
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Publication
Featured researches published by Ryan M. Williams.
Scientific Reports | 2015
Daniel Roxbury; Prakrit V. Jena; Ryan M. Williams; Balázs Enyedi; Philipp Niethammer; Stéphane Marcet; Marc Verhaegen; Sébastien Blais-Ouellette; Daniel A. Heller
The intrinsic near-infrared photoluminescence (fluorescence) of single-walled carbon nanotubes exhibits unique photostability, narrow bandwidth, penetration through biological media, environmental sensitivity, and both chromatic variety and range. Biomedical applications exploiting this large family of fluorophores will require the spectral and spatial resolution of individual (n,m) nanotube species’ fluorescence and its modulation within live cells and tissues, which is not possible with current microscopy methods. We present a wide-field hyperspectral approach to spatially delineate and spectroscopically measure single nanotube fluorescence in living systems. This approach resolved up to 17 distinct (n,m) species (chiralities) with single nanotube spatial resolution in live mammalian cells, murine tissues ex vivo, and zebrafish endothelium in vivo. We anticipate that this approach will facilitate multiplexed nanotube imaging in biomedical applications while enabling deep-tissue optical penetration, and single-molecule resolution in vivo.
Nature Biomedical Engineering | 2017
Jackson Dean Harvey; Prakrit V. Jena; Hanan A. Baker; Gül H. Zerze; Ryan M. Williams; Thomas Vito Galassi; Daniel Roxbury; Jeetain Mittal; Daniel A. Heller
MicroRNAs and other small oligonucleotides in biofluids are promising disease biomarkers, yet conventional assays require complex processing steps that are unsuitable for point-of-care testing or for implantable or wearable sensors. Single-walled carbon nanotubes are an ideal material for implantable sensors, owing to their emission in the near-infrared spectral region, photostability and exquisite sensitivity. Here, we report an engineered carbon-nanotube-based sensor capable of real-time optical quantification of hybridization events of microRNA and other oligonucleotides. The mechanism of the sensor arises from competitive effects between displacement of both oligonucleotide charge groups and water from the nanotube surface, which result in a solvatochromism-like response. The sensor, which allows for detection via single-molecule sensor elements and for multiplexing by using multiple nanotube chiralities, can monitor toehold-based strand-displacement events, which reverse the sensor response and regenerate the sensor complex. We also show that the sensor functions in whole urine and serum, and can non-invasively measure DNA and microRNA after implantation in live mice.
Kidney International | 2016
Ryan M. Williams; Edgar A. Jaimes; Daniel A. Heller
Nanomedicines have been the subject of great interest for the treatment, diagnosis, and research of disease; however, few specifically address kidney disorders. Nanotechnology can confer significant benefits to medicine, such as the targeted delivery of drugs to specific tissues. Nanomedicines in the clinic have increased drug solubility, reduced off-target side effects, and provided novel diagnostic tools. There is an increasing cohort of nanomaterials that may have implications for kidney disease. Here, we review nanomaterial properties that are potentially applicable to kidney research and therapy, and we highlight clinical areas of need that may benefit from kidney nanomedicines.
Science Advances | 2018
Ryan M. Williams; Christopher Lee; Thomas Vito Galassi; Jackson Dean Harvey; Rachel Leicher; Maria Sirenko; Madeline A. Dorso; Janki Shah; Narciso Olvera; Fanny Dao; Douglas A. Levine; Daniel A. Heller
Ovarian cancer biomarker detection using a novel nanosensor implant in live mice. Patients with high-grade serous ovarian carcinoma (HGSC) exhibit poor 5-year survival rates, which may be significantly improved by early-stage detection. The U.S. Food and Drug Administration–approved biomarkers for HGSC—CA-125 (cancer antigen 125) and HE4 (human epididymis protein 4)—do not generally appear at detectable levels in the serum until advanced stages of the disease. An implantable device placed proximal to disease sites, such as in or near the fallopian tube, ovary, uterine cavity, or peritoneal cavity, may constitute a feasible strategy to improve detection of HGSC. We engineered a prototype optical sensor composed of an antibody-functionalized carbon nanotube complex, which responds quantitatively to HE4 via modulation of the nanotube optical bandgap. The complexes measured HE4 with nanomolar sensitivity to differentiate disease from benign patient biofluids. The sensors were implanted into four models of ovarian cancer, within a semipermeable membrane, enabling the optical detection of HE4 within the live animals. We present the first in vivo optical nanosensor capable of noninvasive cancer biomarker detection in orthotopic models of disease.
Hypertension | 2018
Ryan M. Williams; Janki Shah; Helen S. Tian; Xi Chen; Frederic Geissmann; Edgar A. Jaimes; Daniel A. Heller
Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases.
Journal of Materials Chemistry B | 2017
Januka Budhathoki-Uprety; Jackson Dean Harvey; Elizabeth Isaac; Ryan M. Williams; Thomas Vito Galassi; Rachel E Langenbacher; Daniel A. Heller
Carbon nanotube-based molecular probes, imaging agents, and biosensors in cells and in vivo continue to garner interest as investigational tools and clinical devices due to their unique photophysical properties. Surface chemistry modulation of nanotubes plays a critical role in determining stability and interaction with biological systems both in vitro and in vivo. Among the many parameters that influence the biological fate of nanomaterials, surface charge is particularly influential due to direct electrostatic interactions with components of the cell membrane as well as proteins in the serum, which coat the nanoparticle surface in a protein corona and alter nanoparticle-cell interactions. Here, we modulated functional moieties on a helical polycarbodiimide polymer backbone that non-covalently suspended the nanotubes in aqueous media. By derivatizing the polymer with either primary amine or carboxylic acid side chains, we obtained nanotube complexes that present net surface charges of opposite polarity at physiological pH. Using these materials, we found that the uptake of carbon nanotubes in these cells is highly dependent on charge, with cationic nanotubes efficiently internalized into cells compared to the anionic nanotubes. Furthermore, we found that serum proteins drastically influenced cell uptake of the anionic nanotubes, while the effect was not prominent for the cationic nanotubes. Our findings have implications for improved engineering of drug delivery devices, molecular probes, and biosensors.
Proceedings of SPIE | 2016
Daniel A. Heller; Daniel Roxbury; Prakrit V. Jena; Ryan M. Williams; Balázs Enyedi; Philipp Niethammer; Stéphane Marcet; Francesca Mangiarini; Marc Verhaegen; Sebastien Blais-Ouellette
The intrinsic near-infrared photoluminescence (fluorescence) of single-walled carbon nanotubes exhibits unique photostability, narrow bandwidth, penetration through biological media, environmental sensitivity, and both chromatic variety and range. Biomedical applications exploiting this large family of fluorophores will require the spectral and spatial resolution of individual (n,m) nanotube species’ fluorescence and its modulation within live cells and tissues, which is not possible with current microscopy methods. We present a wide-field hyperspectral approach to spatially delineate and spectroscopically measure single nanotube fluorescence in living systems. This approach resolved up to 17 distinct (n,m) species (chiralities) with single nanotube spatial resolution in live mammalian cells, murine tissues ex vivo, and zebrafish endothelium in vivo. We anticipate that this approach will facilitate multiplexed nanotube imaging in biomedical applications while enabling deep-tissue optical penetration, exceptional photostability, and single-molecule resolution in vivo.
Nano Letters | 2015
Ryan M. Williams; Janki Shah; Brandon D. Ng; Denise R. Minton; Lorraine J. Gudas; Christopher Y. Park; Daniel A. Heller
ACS Sensors | 2018
Ryan M. Williams; Christopher Lee; Daniel A. Heller
231st ECS Meeting (May 28 - June 1, 2017) | 2017
Jackson Dean Harvey; Hanan A. Baker; Thomas Vito Galassi; Ryan M. Williams; Daniel A. Heller