New“all-in-one”theranostic systems,combining a magnetic resonance imaging(MRI)contrast agent with a biphotonic photodynamic therapy(2P-PDT)photosensitiser generating cytotoxic singlet oxygen,were envisaged and synth...New“all-in-one”theranostic systems,combining a magnetic resonance imaging(MRI)contrast agent with a biphotonic photodynamic therapy(2P-PDT)photosensitiser generating cytotoxic singlet oxygen,were envisaged and synthesised.They are based on azamacrocycles,regiospecifically functionalised by two-photon PDTπ-conjugated dibromobenzene-picolinate photosensitisers and acetate,able to complex gadolinium(III)and allow an MRI signal.Our approach was to use two different macrocyclic platforms,tacn and pyclen,for modulating simultaneously the structures,properties and solubility of the complexes.Photophysical properties of the ligands and their gadolinium(III)complexes were fully investigated.The Gd^(3+)-pyclen derivative showed the best water solubility and the greatest value of singlet oxygen generation of the series withΦ_(Δ)=0.53 enabling in vitro studies.The biological PDT activity under mono and biphotonic excitation was evaluated in human breast cancer cells(MCF-7).While a very low dark toxicity was observed,an almost total cell death was induced after only 3 successive irradiations of 1.57 s.Finally,its relaxivity was measured in a DMSO/H_(2)O solvent mixture with r_(1p)=11.21 and r_(2p)=24.60 mM^(-1)s^(-1)at 3.0 T and T_(1)-and T_(2)-weighted phantom MR images were obtained highlighting a first generation of“all-in-one”PDT/MRI theranostic agents.展开更多
基金ANR(SADAM ANR-16-CE07-0015-02)Hungarian National Research,Development and Innovation Office(NKFIH K-128201 and 134694 projects)+1 种基金EU and co-financed by the European Regional Development Fund under the project GINOP-2.3.2-15-2016-00008French National Research Agency(ANR-10-INBS-04,«Investments for the future»)。
文摘New“all-in-one”theranostic systems,combining a magnetic resonance imaging(MRI)contrast agent with a biphotonic photodynamic therapy(2P-PDT)photosensitiser generating cytotoxic singlet oxygen,were envisaged and synthesised.They are based on azamacrocycles,regiospecifically functionalised by two-photon PDTπ-conjugated dibromobenzene-picolinate photosensitisers and acetate,able to complex gadolinium(III)and allow an MRI signal.Our approach was to use two different macrocyclic platforms,tacn and pyclen,for modulating simultaneously the structures,properties and solubility of the complexes.Photophysical properties of the ligands and their gadolinium(III)complexes were fully investigated.The Gd^(3+)-pyclen derivative showed the best water solubility and the greatest value of singlet oxygen generation of the series withΦ_(Δ)=0.53 enabling in vitro studies.The biological PDT activity under mono and biphotonic excitation was evaluated in human breast cancer cells(MCF-7).While a very low dark toxicity was observed,an almost total cell death was induced after only 3 successive irradiations of 1.57 s.Finally,its relaxivity was measured in a DMSO/H_(2)O solvent mixture with r_(1p)=11.21 and r_(2p)=24.60 mM^(-1)s^(-1)at 3.0 T and T_(1)-and T_(2)-weighted phantom MR images were obtained highlighting a first generation of“all-in-one”PDT/MRI theranostic agents.
