Abstract
Photodynamic therapy for deep-lying lesions needs an appropriate imaging modality, precise evaluation of tissue oxygen and an effective photosensitizer. Gadolinium based metalloporphyrins Gd(III)-HMME is proposed in this study as a potential multifunctional theranostic agent, as photosensitizer, ratiometric oxygen sensor and MRI contrast agent. The time resolved spectroscopy revealed the luminescence peak of Gd(III)-HMME at 710 and 779 nm with a lifetime of 64 μs in oxygen-free methanol to be phosphorescent. This phosphorescence is strongly dependent on dissolved oxygen concentration. Its intensity in oxygen saturated methanol solution is 21% of that in deoxygenated solution. The singlet oxygen quantum yields ΦΔ of HMME and Gd(III)-HMME in air saturated methanol solution were determined to be 0.79 and 0.40 respectively using comparative spectra method. These phenomena indicate that the oxygen sensibility and production of singlet oxygen of Gd(III)-HMME can fulfill the requirement of PDT treatment.
Highlights
Photodynamic therapy (PDT) and fluorescence imaging has long been used for treatment and diagnosis of superficial cancer
When PSs are exposed to light of appropriate wavelength, they produce highly cytotoxic singlet oxygen (1O2) to destruct the diseased tissue and the fluorescence could be used for diagnosis and image guided resection [1]
Clinical applications of PDT treatment are restricted by the limited penetration of light
Summary
Photodynamic therapy (PDT) and fluorescence imaging has long been used for treatment and diagnosis of superficial cancer. MRI guided diffuse optical spectroscopy (DOS) and fluorescence tomography imaging (FTI) [4] have been developed for diagnosis of tumors With these technologies, the three-dimensional (3D) dosimetric planning of interstitial PDT can be realized. Metalloporphyrins are reported to be necrosis-avid rather than tumor-avid, which means that metalloporphyrins based photosensitizers are only suitable for malignant tumors because in premalignant cancer, there are very few necrotic cells This property enables metalloporphyrins to find applications in atherosclerotic plaque imaging [15], myocardial infarction delineation [16], etc. Gadolinium metalated hematoporphyrin methyl ether Gd(III)-HMME was synthesized and characterized with mass spectra and UV-visible spectra Both the molecular weight and the electronic structure confirmed the successful synthesis of the metalloporphyrins. The synergistic effect of oxygen sensing capability, photosensitivity, MRI enhancement, cell permeability and the necrosis affinity would give Gd(III)-HMME a wide potential application prospect
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