Mitochondria
play a critical role in tumorigenesis. Targeting mitochondria
and disturbing related events have been emerging as a promising way
for chemotherapy. In this work, two binuclear rhenium(I) tricarbonyl
complexes of the general formula [Re2(CO)6(dip)2L](PF6)2 (dip = 4,7-diphenyl-1,10-phenanthroline;
L = 4,4′-azopyridine (ReN) or 4,4′-dithiodipyridine
(ReS)) were synthesized and characterized. ReN and ReS can react with glutathione (GSH). They exhibit
good in vitro anticancer activity against cancer cell lines screened.
Besides, they can target mitochondria, cause oxidative stress, and
disturb GSH metabolism. Both ReN and ReS can induce necroptosis and caspase-dependent apoptosis simultaneously.
We also demonstrate that ReN and ReS can
inhibit tumor growth in nude mice bearing carcinoma xenografts. Our
study shows the potential of Re(I) complexes as chemotherapeutic agents
to kill cancer cells via a mitochondria-to-cellular redox strategy.
Ruthenium complexes are promising photosensitizers (PSs), but their clinical applications have many limitations. Here, a multifunctional nano‐platform PDA‐Pt‐CD@RuFc formed by platinum‐decorated and cyclodextrin (CD)‐modified polydopamine (PDA) nanoparticles (NPs) loaded with a ferrocene‐appended ruthenium complex (RuFc) is reported. The NPs can successfully deliver RuFc to the tumor sites. The release of RuFc from the NPs can be triggered by low pH, photothermal heating, and H2O2. The combined photodynamic and photothermal therapy (PDT‐PTT) mediated by PDA‐Pt‐CD@RuFc NPs can overcome the hypoxic environment of tumors from several aspects. First, the platinum NPs can catalyze H2O2 to produce O2. Second, vasodilation caused by photothermal heating can sustain the oxygen supplement. Third, PDT exerted by RuFc can also occur through the non‐oxygen‐dependent Fenton reaction. Due to the presence of PDA, platinum NPs, and RuFc, the nanosystem can be used in multimodal imaging including photothermal, photoacoustic, and computed tomography imaging. The NPs can be excited by the near‐infrared two‐photon light source. Moreover, the combined treatment can improve the tumor microenvironments to obtain an optimized combined therapeutic effect. In summary, this study presents a tumor‐microenvironment‐adaptive strategy to optimize the potential of ruthenium complexes as PSs from multiple aspects.
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