ORCID Profile
0000-0002-4049-4151
Current Organisations
Institut de Cancérologie de Strasbourg Europe
,
Centre Paul Strauss
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Publications
A Novel Near‐IR Absorbing Ruthenium(II) Complex as Photosensitizer for Photodynamic Therapy and its Cetuximab Bioconjugates
Publisher: Wiley
Date: 05-07-2023
Abstract: A novel Ru(II) cyclometalated photosensitizer (PS), Ru‐NH 2 , for photodynamic therapy (PDT) of formula [Ru(appy)(bphen) 2 ]PF 6 (where appy=4‐amino‐2‐phenylpyridine and bphen=bathophenanthroline) and its cetuximab (CTX) bioconjugates, Ru‐Mal‐CTX and Ru‐BAA‐CTX (where Mal=maleimide and BAA=benzoylacrylic acid) were synthesised and characterised. The photophysical properties of Ru‐NH 2 revealed absorption maxima around 580 nm with an absorption up to 725 nm. The generation of singlet oxygen ( 1 O 2 ) upon light irradiation was confirmed with a 1 O 2 quantum yield of 0.19 in acetonitrile. Preliminary in vitro experiments revealed the Ru‐NH 2 was nontoxic in the dark in CT‐26 and SQ20B cell lines but showed outstanding phototoxicity when irradiated, reaching interesting phototoxicity indexes (PI) at 670 nm, and at 740 nm for CT‐26 cells and with NIR light in SQ20B cells. The antibody CTX was successfully attached to the complexes in view of the selective delivery of the PS to cancer cells. Up to four ruthenium fragments were anchored to the antibody (Ab), as confirmed by MALDI‐TOF mass spectrometry. Nonetheless, the bioconjugates were not as photoactive as the Ru‐NH 2 complex.
Antitumor Immune Response Triggered by Metal-Based Photosensitizers for Photodynamic Therapy: Where Are We?
Publisher: MDPI AG
Date: 26-10-2021
DOI: 10.3390/PHARMACEUTICS13111788
Abstract: Metal complexes based on transition metals have rich photochemical and photophysical properties that are derived from a variety of excited state electronic configurations triggered by visible and near-infrared light. These properties can be exploited to produce powerful energy and electron transfer processes that can lead to oxygen-(in)dependent photobiological activity. These principles are the basis of photodynamic therapy (PDT), which is a clinically approved treatment that offers a promising, effective, and noninvasive complementary treatment or even an alternative to treat several types of cancers. PDT is based on a reaction involving a photosensitizer (PS), light, and oxygen, which ultimately generates cytotoxic reactive oxygen species (ROS). However, skin photosensitivity, due to the accumulation of PSs in skin cells, has h ered, among other elements, its clinical development and application. Therefore, these is an increasing interest in the use of (metal-based) PSs that are more specific to tumor cells. This may increase efficacy and corollary decrease side-effects. To this end, metal-containing nanoparticles with photosensitizing properties have recently been developed. In addition, several studies have reported that the use of immunogenic/immunomodulatory metal-based nanoparticles increases the antitumor efficacy of immune-checkpoint inhibitor-based immunotherapy mediated by anti-PD-(L)1 or CTLA-4 antibodies. In this review, we discuss the main metal complexes used as PDT PSs. Lastly, we review the preclinical studies associated with metal-based PDT PSs and immunotherapies. This therapeutic association could stimulate PDT.
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Related Funding Activities
No related grants have been discovered for Alain Jung.