Dataset Information

Novel Peptide NIRF Optical Surgical Navigation Agents for HNSCC.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) survival rates have not improved in a decade, with a 63% 5-year recurrence rate after surgery, making HNSCC a compelling indication for optical surgical navigation (OSN). A promising peptide, HN1, targeted and internalized in human HNSCC cells in multiple laboratories, but was slow (24 h) to accumulate. We modified HN1 and explored structural variables to improve the uptake kinetics and create IRdye800 adducts useful for OSN. Eleven new molecules were synthesized and characterized chemically, in human HNSCC cells (Cal 27), and in HNSCC xenograft mice. Cal 27 flank xenografts in Balb/c nude mice were imaged for 3-48 h after 40 nmol intravenous doses of IR800-labeled molecules. Cell uptake kinetics in the 1-2 h window incubated at 1-10 μM were independent of the dye label (FITC, Cy5, or IR800), but increased markedly with additional N-terminal lipophilic substitution, and after resequencing the peptide to separate polar amino acids and move the lysine-dye more centrally. Microscopy confirmed the strong Cal 27 cell binding and demonstrated primarily cytosolic and membrane localization of the fastest peptide, 4Iphf-HN17. 4Iph-HN17-IR800 showed 26-fold greater rate of uptake in cells than HN1-IR800, and far stronger OSN imaging intensity and tumor to background contrast in mice, suggesting that the new peptide is a promising candidate for OSN of HNSCC.

SUBMITTER: Ding H

PROVIDER: S-EPMC6749330 | biostudies-other | 2019 Aug

REPOSITORIES: biostudies-other

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Novel Peptide NIRF Optical Surgical Navigation Agents for HNSCC.

Ding Haiming H Kothandaraman Shankaran S Gong Li L Wright Chadwick L CL Pan Quintin Q Teknos Theodore T Tweedle Michael F MF

Molecules (Basel, Switzerland) 20190823 17

Head and neck squamous cell carcinoma (HNSCC) survival rates have not improved in a decade, with a 63% 5-year recurrence rate after surgery, making HNSCC a compelling indication for optical surgical navigation (OSN). A promising peptide, HN1, targeted and internalized in human HNSCC cells in multiple laboratories, but was slow (24 h) to accumulate. We modified HN1 and explored structural variables to improve the uptake kinetics and create IRdye800 adducts useful for OSN. Eleven new molecules wer ...[more]

PMID: 31450798

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Project description:PURPOSE:This paper introduces the SciKit-Surgery libraries, designed to enable rapid development of clinical applications for image-guided interventions. SciKit-Surgery implements a family of compact, orthogonal, libraries accompanied by robust testing, documentation, and quality control. SciKit-Surgery libraries can be rapidly assembled into testable clinical applications and subsequently translated to production software without the need for software reimplementation. The aim is to support translation from single surgeon trials to multicentre trials in under 2 years. METHODS:At the time of publication, there were 13 SciKit-Surgery libraries provide functionality for visualisation and augmented reality in surgery, together with hardware interfaces for video, tracking, and ultrasound sources. The libraries are stand-alone, open source, and provide Python interfaces. This design approach enables fast development of robust applications and subsequent translation. The paper compares the libraries with existing platforms and uses two example applications to show how SciKit-Surgery libraries can be used in practice. RESULTS:Using the number of lines of code and the occurrence of cross-dependencies as proxy measurements of code complexity, two example applications using SciKit-Surgery libraries are analysed. The SciKit-Surgery libraries demonstrate ability to support rapid development of testable clinical applications. By maintaining stricter orthogonality between libraries, the number, and complexity of dependencies can be reduced. The SciKit-Surgery libraries also demonstrate the potential to support wider dissemination of novel research. CONCLUSION:The SciKit-Surgery libraries utilise the modularity of the Python language and the standard data types of the NumPy package to provide an easy-to-use, well-tested, and extensible set of tools for the development of applications for image-guided interventions. The example application built on SciKit-Surgery has a simpler dependency structure than the same application built using a monolithic platform, making ongoing clinical translation more feasible.

Dataset Information

Novel Peptide NIRF Optical Surgical Navigation Agents for HNSCC.

Publications

Novel Peptide NIRF Optical Surgical Navigation Agents for HNSCC.

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