当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Photodynamic molecular beacon as an activatable photosensitizer based on protease-controlled singlet oxygen quenching and activation.

Photodynamic molecular beacon as an activatable photosensitizer based on protease-controlled singlet oxygen quenching and activation.

Abstract：

:Molecular beacons are FRET-based target-activatable probes. They offer control of fluorescence emission in response to specific cancer targets, thus are useful tools for in vivo cancer imaging. Photodynamic therapy (PDT) is a cell-killing process by light activation of a photosensitizer (PS) in the presence of oxygen. The key cytotoxic agent is singlet oxygen ((1)O(2)). By combining these two principles (FRET and PDT), we have introduced a concept of photodynamic molecular beacons (PMB) for controlling the PS's ability to generate (1)O(2) and, ultimately, for controlling its PDT activity. The PMB comprises a disease-specific linker, a PS, and a (1)O(2) quencher, so that the PS's photoactivity is silenced until the linker interacts with a target molecule, such as a tumor-associated protease. Here, we report the full implementation of this concept by synthesizing a matrix metalloproteinase-7 (MMP7)-triggered PMB and achieving not only MMP7-triggered production of (1)O(2) in solution but also MMP7-mediated photodynamic cytotoxicity in cancer cells. Preliminary in vivo studies also reveal the MMP7-activated PDT efficacy of this PMB. This study validates the core principle of the PMB concept that selective PDT-induced cell death can be achieved by exerting precise control of the PS's ability to produce (1)O(2) by responding to specific cancer-associated biomarkers. Thus, PDT selectivity will no longer depend solely on how selectively the PS can be delivered to cancer cells. Rather, it will depend on how selective a biomarker is to cancer cells, and how selective the interaction of PMB is to this biomarker.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Zheng G,Chen J,Stefflova K,Jarvi M,Li H,Wilson BC

doi

10.1073/pnas.0611142104

subject

Has Abstract

pub_date

2007-05-22 00:00:00

pages

8989-94

issue

21

eissn

0027-8424

issn

1091-6490

pii

0611142104

journal_volume

104

pub_type

杂志文章

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