Following nanomedicine activation with magnetic resonance imaging: why, how, and what’s next?

Abstract

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Transition Metal Complexes and Photodynamic Therapy from a Tumor-Centered Approach: Challenges, Opportunities, and Highlights from the Development of TLD1433

“…The large quantum yields for triplet state formation and the characteristic reactivities of the different excited-state configurations offer the opportunity to rationally design transition metal complexes with desirable photobiological mechanisms that are simply not possible with organic photosensitizers. The most studied transition metal complexes for this purpose are based on Pt(IV), Ru(II), and Rh(III), [52][53][54][55][56][57][58][59] followed more recently by Ir(III), 60,61 and finally Os(II). 62 The mode of light-controlled cytotoxicity generally falls into one of the following categories: (1) photosensitization reactions that involve ROS (PDT), (2) photosensitization reactions that do not involve ROS, (3) photothermal processes (photothermal therapy, PTT), and (4) photodissociation reactions involving the metal or photocleavage reactions on the ligand.…”

“…The field is too large to cover in a single review, but a few recent accounts have covered a lot of ground. [53][54][55][56][72][73][74][75] For this review, we have focused on a few examples to demonstrate the structural features that control the nature of the lowest-energy triplet excited states in Ru(II) complexes (see Chart 1 and the corresponding jablonski diagrams in Scheme 3). We also limit the discussion to the family of tris-bidentate diimine chelates of Ru(II), of which our own TLD1433 is a member, and the aspects of designing these complexes.…”

“…It is worth noting that there are a number other elegant examples of oxygen-independent light-responsive Ru(II) complexes, where the metal center itself participates in the photochemical reaction through 3 MC states (as discussed above) as well as those where the photochemical reaction can take place on a ligand through organic photochemical reactions. Some of these approaches are highlighted in a recent 2O17 review by Szymanski, 53 and elsewhere. 58,75…”

Photo-controlled delivery of a potent analogue of doxorubicin

“…A more recent alternative to PDT is photoactivated chemotherapy where a standard cancer chemotherapeutic is converted into a light-activatable form. 11,12 A common strategy is to attach the molecule to a photocage, 13 a re-leasable group that blocks the anticancer agent’s activity until illumination. We and others have pursued this strategy by caging conventional anticancer agents such as doxorubicin, cisplatin, etc.…”

“…We and others have pursued this strategy by caging conventional anticancer agents such as doxorubicin, cisplatin, etc. 12,14–21 Each of these advances has focused on delivery of anticancer agents with moderate cytotoxicity. Release of a more potent drug should enable deeper tissue activation as less efficient release should still lead to the cytotoxic effect.…”