Combining imaging and anticancer properties with new heterobimetallic Pt(ii)/M(i) (M = Re,99mTc) complexes.
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 by99mTc 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 (99mTc) 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.
Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela LRS, Portugal. apaulo@ctn.tecnico.ulisboa.pt.
Letícia
L
Quental
Paula
P
Raposinho
Filipa
F
Mendes
Isabel
I
Santos
Carmen
C
Navarro-Ranninger
Amparo
A
Alvarez-Valdes
Huaiyi
H
Huang
Hui
H
Chao
Riccardo
R
Rubbiani
Gilles
G
Gasser
Adoración G
AG
Quiroga
António
A
Paulo
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010984:Platinum / Q000737:chemistry*; D011877:Radionuclide Imaging / Q000379:methods*; D012211:Rhenium / Q000737:chemistry*; D026082:Singlet Oxygen / Q000378:metabolism; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D026082:Singlet Oxygen; D010984:Platinum; D012211:Rhenium; D013667:Technetium