High-Contrast Fluorescence Detection of Metastatic Breast Cancer Including Bone and Liver Micrometastases via Size-Controlled pH-Activatable Water-Soluble Probes

Hu Xiong, Hao Zuo, Yunfeng Yan, Gino Occhialini, Kejin Zhou, Yihong Wan, Daniel J. Siegwart

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Breast cancer metastasis is the major cause of cancer death in women worldwide. Early detection would save many lives, but current fluorescence imaging probes are limited in their detection ability, particularly of bone and liver micrometastases. Herein, probes that are capable of imaging tiny (<1 mm) micrometastases in the liver, lung, pancreas, kidneys, and bone, that have disseminated from the primary site, are reported. The influence of the poly(ethylene glycol) (PEG) chain length on the performance of water-soluble, pH-responsive, near-infrared 4,4′-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) probes is systematically investigated to demonstrate that PEG tuning can provide control over micrometastasis tracking with high tumor-to-background contrast (up to 12/1). Optimized probes can effectively visualize tumor boundaries and successfully detect micrometastases with diameters <1 mm. The bone-metastasis-targeting ability of these probes is further enhanced by covalent functionalization with bisphosphonate. This improved detection of both bone and liver micrometastases (<2 mm) with excellent tumor-to-normal contrast (5.2/1). A versatile method is thus introduced to directly synthesize modular water-soluble probes with broad potential utility. Through a single intravenous injection, these materials can image micrometastases in multiple organs with spatiotemporal resolution. They thus hold promise for metastasis diagnosis, image-guided surgery, and theranostic PEGylated drug therapies.

Original languageEnglish (US)
JournalAdvanced Materials
DOIs
StateAccepted/In press - 2017

Fingerprint

Liver
Bone
Fluorescence
Water
Polyethylene glycols
Tumors
Drug therapy
Imaging techniques
Diphosphonates
Chain length
Surgery
Tuning
Infrared radiation
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene

Keywords

  • Fluorescence
  • Imaging
  • Metastasis
  • PH
  • Water-soluble probes

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

Cite this

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title = "High-Contrast Fluorescence Detection of Metastatic Breast Cancer Including Bone and Liver Micrometastases via Size-Controlled pH-Activatable Water-Soluble Probes",
abstract = "Breast cancer metastasis is the major cause of cancer death in women worldwide. Early detection would save many lives, but current fluorescence imaging probes are limited in their detection ability, particularly of bone and liver micrometastases. Herein, probes that are capable of imaging tiny (<1 mm) micrometastases in the liver, lung, pancreas, kidneys, and bone, that have disseminated from the primary site, are reported. The influence of the poly(ethylene glycol) (PEG) chain length on the performance of water-soluble, pH-responsive, near-infrared 4,4′-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) probes is systematically investigated to demonstrate that PEG tuning can provide control over micrometastasis tracking with high tumor-to-background contrast (up to 12/1). Optimized probes can effectively visualize tumor boundaries and successfully detect micrometastases with diameters <1 mm. The bone-metastasis-targeting ability of these probes is further enhanced by covalent functionalization with bisphosphonate. This improved detection of both bone and liver micrometastases (<2 mm) with excellent tumor-to-normal contrast (5.2/1). A versatile method is thus introduced to directly synthesize modular water-soluble probes with broad potential utility. Through a single intravenous injection, these materials can image micrometastases in multiple organs with spatiotemporal resolution. They thus hold promise for metastasis diagnosis, image-guided surgery, and theranostic PEGylated drug therapies.",
keywords = "Fluorescence, Imaging, Metastasis, PH, Water-soluble probes",
author = "Hu Xiong and Hao Zuo and Yunfeng Yan and Gino Occhialini and Kejin Zhou and Yihong Wan and Siegwart, {Daniel J.}",
year = "2017",
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T1 - High-Contrast Fluorescence Detection of Metastatic Breast Cancer Including Bone and Liver Micrometastases via Size-Controlled pH-Activatable Water-Soluble Probes

AU - Xiong, Hu

AU - Zuo, Hao

AU - Yan, Yunfeng

AU - Occhialini, Gino

AU - Zhou, Kejin

AU - Wan, Yihong

AU - Siegwart, Daniel J.

PY - 2017

Y1 - 2017

N2 - Breast cancer metastasis is the major cause of cancer death in women worldwide. Early detection would save many lives, but current fluorescence imaging probes are limited in their detection ability, particularly of bone and liver micrometastases. Herein, probes that are capable of imaging tiny (<1 mm) micrometastases in the liver, lung, pancreas, kidneys, and bone, that have disseminated from the primary site, are reported. The influence of the poly(ethylene glycol) (PEG) chain length on the performance of water-soluble, pH-responsive, near-infrared 4,4′-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) probes is systematically investigated to demonstrate that PEG tuning can provide control over micrometastasis tracking with high tumor-to-background contrast (up to 12/1). Optimized probes can effectively visualize tumor boundaries and successfully detect micrometastases with diameters <1 mm. The bone-metastasis-targeting ability of these probes is further enhanced by covalent functionalization with bisphosphonate. This improved detection of both bone and liver micrometastases (<2 mm) with excellent tumor-to-normal contrast (5.2/1). A versatile method is thus introduced to directly synthesize modular water-soluble probes with broad potential utility. Through a single intravenous injection, these materials can image micrometastases in multiple organs with spatiotemporal resolution. They thus hold promise for metastasis diagnosis, image-guided surgery, and theranostic PEGylated drug therapies.

AB - Breast cancer metastasis is the major cause of cancer death in women worldwide. Early detection would save many lives, but current fluorescence imaging probes are limited in their detection ability, particularly of bone and liver micrometastases. Herein, probes that are capable of imaging tiny (<1 mm) micrometastases in the liver, lung, pancreas, kidneys, and bone, that have disseminated from the primary site, are reported. The influence of the poly(ethylene glycol) (PEG) chain length on the performance of water-soluble, pH-responsive, near-infrared 4,4′-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) probes is systematically investigated to demonstrate that PEG tuning can provide control over micrometastasis tracking with high tumor-to-background contrast (up to 12/1). Optimized probes can effectively visualize tumor boundaries and successfully detect micrometastases with diameters <1 mm. The bone-metastasis-targeting ability of these probes is further enhanced by covalent functionalization with bisphosphonate. This improved detection of both bone and liver micrometastases (<2 mm) with excellent tumor-to-normal contrast (5.2/1). A versatile method is thus introduced to directly synthesize modular water-soluble probes with broad potential utility. Through a single intravenous injection, these materials can image micrometastases in multiple organs with spatiotemporal resolution. They thus hold promise for metastasis diagnosis, image-guided surgery, and theranostic PEGylated drug therapies.

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