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In vivo cation exchange in quantum dots for tumor-specific imaging.

ABSTRACT: In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intravenously delivered into orthotopic breast and pancreas tumors in mice by using the tumor-penetrating iRGD peptide. Subsequent etching quenches excess quantum dots, leaving a highly tumor-specific signal provided by the intact quantum dots remaining in the extravascular tumor cells and fibroblasts. No toxicity is noted. The system also facilitates the detection of peritoneal tumors with high specificity upon intraperitoneal tumor targeting and selective etching of excess untargeted quantum dots. In vivo cation exchange may be a promising strategy to enhance specificity of tumor imaging.The imaging of tumors in vivo using nanoprobes has been challenging due to the lack of sufficient tumor specificity. Here, the authors develop a tumor-specific quantum dot system that permits in vivo cation exchange to achieve selective background quenching and high tumor-specific imaging.

SUBMITTER: Liu X

PROVIDER: S-EPMC5571182 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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In vivo cation exchange in quantum dots for tumor-specific imaging.

Liu Xiangyou X Braun Gary B GB Qin Mingde M Ruoslahti Erkki E Sugahara Kazuki N KN

Nature communications 20170824 1

In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intra ...[more]

PMID: 28839238

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Project description:IntroductionThe detection of circulating tumor cells (CTCs) is very important for cancer diagnosis. CTCs can travel from primary tumors through the circulation to form secondary tumor colonies via bloodstream extravasation. The number of CTCs has been used as an indicator of cancer progress. However, the population of CTCs is very heterogeneous. It is very challenging to identify CTC subpopulations such as cancer stem cells (CSCs) with high metastatic potential, which are very important for cancer diagnostic management.ResultsWe report a study of real-time CTC and CSC imaging in the bloodstreams of living animals using multi-photon microscopy and antibody conjugated quantum dots. We have developed a cancer model for noninvasive imaging wherein pancreatic cancer cells expressing fluorescent proteins were subcutaneously injected into the earlobes of mice and then formed solid tumors. When the cancer cells broke away from the solid tumor, CTCs with fluorescent proteins in the bloodstream at different stages of development could be monitored noninvasively in real time. The number of CTCs observed in the blood vessels could be correlated to the tumor size in the first month and reached a maximum value of approximately 100 CTCs/min after 5 weeks of tumor inoculation. To observe CTC subpopulations, conjugated quantum dots were used. It was found that cluster of differentiation (CD)24+ CTCs can move along the blood vessel walls and migrate to peripheral tissues. CD24+ cell accumulation on the solid tumors' sides was observed, which may provide valuable insight for designing new drugs to target cancer subpopulations with high metastatic potential. We also demonstrated that our system is capable of imaging a minor population of cancer stem cells, CD133+ CTCs, which are found in 0.7% of pancreatic cancer cells and 1%-3% of solid tumors in patients.ConclusionsWith the help of quantum dots, CTCs with higher metastatic potential, such as CD24+ and CD133+ CTCs, have been identified in living animals. Using our approach, it may be possible to investigate detailed metastatic mechanism such as tumor cell extravasation to the blood vessels. In addition, the number of observed CTCs in the blood stream could be correlated with tumor stage in the early stage of cancer.

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In vivo cation exchange in quantum dots for tumor-specific imaging.

Publications

In vivo cation exchange in quantum dots for tumor-specific imaging.

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