Combining imaging and anticancer properties with new heterobimetallic Pt(ii)/M(i) (M = Re, ^99mTc) complexes

Abstract

In this article, we report on the development of new metal-based anticancer agents with imaging, chemotherapeutic and photosensitizing properties. Hence, a new heterobimetallic complex (Pt-LQ-Re) was prepared by connecting a non-conventional trans-chlorido Pt(ii) complex to a photoactive Re tricarbonyl unit (LQ-Re), which can be replaced by Tc to allow for in vivo imaging. We describe the photophysical and biological properties of the new complexes, in the dark and upon light irradiation (DNA interaction, cellular localization and uptake, and cytotoxicity). Furthermore, planar scintigraphic images of mice injected with Pt-LQ-Tc clearly showed that the radioactive compound is taken up by the excretory system organs, namely liver and kidneys, without significant retention in other tissues. All in all, the strategy of conjugating a chemotherapeutic compound with a PDT photosensitizer endows the resulting complexes with an intrinsic cytotoxic activity in the dark, driven by the non-classical platinum core, and a selective activity upon light irradiation. Most importantly, the possibility of integrating a SPECT imaging radiometal (Tc) in the structure of these new heterobimetallic complexes might allow for in vivo non-invasive visualization of their tumoral accumulation, a crucial issue to predict therapeutic outcomes.

Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy

“…Meanwhile, Quental et al (2017) designed a heterobimetallic complex consisting of a Re(I) tricarbonyl core and a platinum-iminedipyridyl group. Addition of platinum into the Re(I) complex (complex 7 ) was found to be capable of improving the toxicity of Re(I) by three folds towards HeLa cell lines (IC 50 from 42.8 µM to 13.5 µM, upon 10 min light irradiation at 350 nm and 2.58 J cm −2 ), achieving a similar photo-index value (PI) to that of the Photofrin (PI: average of 5) [ 35 , 102 , 103 ]. This suggests the potential for improving Re(I)’s phototoxicity via attachment of a Pt(II) cytotoxic complex.…”

Synthesis, Reactivity Studies, and Cytotoxicity of Two trans-Iodidoplatinum(II) Complexes. Does Photoactivation Work?

“…Within the design of novel metallodrugs, the use of activation therapies such as the use of UVA light offers a wide fan of possibilities for metallic complexes such as activation of reactivity [8], change in conformation [9], heterobimetallic complexes with PDT ligands [10] and singlet oxygen producing complexes [11]. Photochemical studies on a selected number of trans iodido complexes initially showed that irradiation induces a faster reaction with CT DNA and a higher amount of Pt bound to DNA.…”

Synthesis, Reactivity Studies and Cytotoxicity of Two Iodidoplatinum(II) Complexes. Does Photoactivation Work?

“…[6] The reconsideration of these iodido derivatives have shown a great impact in the field, and the trend and behavior of these complexes is being reevaluated. [7] Within the design of novel metallodrugs, the use of activation therapies such as the use of UVA light offers a wide fan of possibilities for metallic complexes such as activation of reactivity [8], change in conformation [9], heterobimetallic complexes with PDT ligands [10] and singlet oxygen producing complexes. [11] Photochemical studies on a selected number of trans iodido complexes initially showed that irradiation induces a faster reaction with CT DNA and a higher amount of Pt bound to DNA.…”