"Smart" Metalloporphyrins as Truly Dual Photodynamic Therapeutic and Molecular Imaging Agents

Project: Research project

Project Details

Description

Photodynamic therapy (PDT) has received considerable attention as a promising modality for cancer treatment. This therapy requires a photosensitizer, visible light, and molecular oxygen. Upon irradiation with a specific wavelength, the photosensitizer undergoes a transition from its ground state to an excited singlet state, which may return to its ground state with fluorescence emission or undergoes intersystem crossing to its excited triplet state. This excited triplet state can then reacts with molecular oxygen to generate reactive oxygen species (ROS), such as singlet oxygen (1O2), which causes cellular and tissue damage.

Porphyrin-based photosensitizers, such as haematoporphyrin derivatives (HpD), have been studied extensively and used clinically over the past two decades. Recently, we reported a cell-permeable bifunctional porphyrin-ruthenium(II) polypyridyl complex showing visible fluorescent image and a substantial 1O2 yield under near-infrared (two-photon) excitation simultaneously. But these two functional properties of the PDT agent, i.e., its fluorescence emission, which allows us to monitor its uptake by the tumor, and its 1O2 generation, which leads to cancer cell death, depend on distinct pathways in the channeling of the excitation energy received from photo-irradiation. Thus, the exhibition of these two properties occurs at the expense of each other. This partitioning of photo-excitation energy constitutes a major challenge in the current design of a bifunctional PDT agent. In this work, we propose to solve this problem by engineering separate functional elements into the same porphyrin-based organometallic complex where one element emits fluorescence for imaging purposes when excited at one wavelength and the other element for generating the toxic 1O2 when excited at another wavelength. This strategy provides us a truly dual functional molecule for tumor imaging and photodynamic anti-cancer therapy.

Two proof-of-concept experiments have been performed in our preliminary study. First, we have synthesized porphyrin-based ruthenium(II) complexes and demonstrated their fluorescence emission and singlet oxygen generation independently when irradiated by near-infrared laser at two different wavelengths. Second, the luminescence signal of the ruthenium(II) complexes did not cause any significant cell death, indicating that luminescent imaging of the bifunctional PDT agent can be conducted without producing any cell-killing effect. Inspired by these results, we further propose to investigate the internal energy transfer pathways of these molecules in order to improve their imaging and PDT effects. Elements targeting specific cell death pathways will also be engineered into these dual functional PDT agents for optimal drug efficacy.
StatusFinished
Effective start/end date1/10/1130/09/14

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 7 - Affordable and Clean Energy

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