Induction of immunogenic cell death in cancer cells by a photoactivated platinum(<scp>iv</scp>) prodrug

Novohradský, Vojtěch; Prachařová, Jitka; Kašpárková, Jana; Imberti, Cinzia; Bridgewater, Hannah E.; Sadler, Peter J.; Brabec, Viktor

doi:10.1039/d0qi00991a

Cited by 48 publications

(36 citation statements)

References 47 publications

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“…This is in strong agreement with previous studies on photoactivation of the mixed amine ligand complex trans , trans , trans -[Pt IV (N 3 ) 2 (OH) 2 (py)(NH 3 )], for which increased levels of autophagic proteins were detected in cancer cells, implicating autophagy in cell death. Equally, the possible autophagy observed here is consistent with reported chemotherapeutically-stimulated ICD induced in cancer cells by photoactivated Pt1 …”

Section: Discussionsupporting

confidence: 92%

“…Cytoplasmic vacuoles, traditionally associated with ROS damage and non-apoptotic cell death, were visible even at the lowest concentration (0.25× photoIC 50 , 1.6 μM). These observations are in agreement with the production of N 2 and ROS (perhaps arising from chain reactions of released azidyl radicals) upon irradiation of this class of complexes ,,, and with their cell death mechanisms, likely involving autophagy and immunogenic cell death (ICD) . Interestingly, a large nuclear vacuole surrounded by lipid droplets was observed in a cell treated with 0.5× photoIC 50 (3.2 μM) of Pt2 with irradiation (Figure S19, T14 ).…”

Section: Discussionsupporting

confidence: 82%

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Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes

et al. 2021

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The Pt(IV) prodrug trans, trans, trans-[Pt(pyridine) 2 (N 3 ) 2 (OH) 2 ] (Pt1) and its coumarin derivative trans, trans, trans-[Pt(pyridine) 2 (N 3 ) 2 (OH)(coumarin-3-carboxylate)] (Pt2) are promising agents for photoactivated chemotherapy. These complexes are inert in the dark but release Pt(II) species and radicals upon visible light irradiation, resulting in photocytotoxicity toward cancer cells. Here, we have used synchrotron techniques to investigate the in-cell behavior of these prodrugs and visualize, for the first time, changes in cellular morphology and Pt localization upon treatment with and without light irradiation. We show that photoactivation of Pt2 induces remarkable cellular damage with extreme alterations to multiple cellular components, including formation of vacuoles, while also significantly increasing the cellular accumulation of Pt species compared to dark conditions. X-ray absorption near-edge structure (XANES) measurements in cells treated with Pt2 indicate only partial reduction of the prodrug upon irradiation, highlighting that phototoxicity in cancer cells may involve not only Pt(II) photoproducts but also photoexcited Pt(IV) species.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 82%

Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes

et al. 2021

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“…Separately, Brabec et al 47 reported a photoactivable platinum( iv ) prodrug, 2.7 (designated as complex 1 in the original work) (Fig. 12A).…”

Section: Metal Based Complexes As Icd Inducersmentioning

confidence: 99%

“…This study thus provides support for the emerging impression that autophagy may be playing an essential role in promoting the immunogenic release of ATP from dying cells. Unfortunately, in vivo studies to support the putative benefit of this novel photoactivable approach to ICD induction were not included in the original report 47 or, apparently, been the subject of follow-up efforts.…”

Section: Metal Based Complexes As Icd Inducersmentioning

confidence: 99%

Metal-based anticancer agents as immunogenic cell death inducers: the past, present, and future

et al. 2022

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“…Another strategy employed by Pt drugs, namely, immunogenic cell death induced by photoactive Pt complexes, might be important for antimetastatic activity [76].…”

Section: Metallodrugs Against Migration and Metastatic Processesmentioning

confidence: 99%

Metallodrugs: an approach against invasion and metastasis in cancer treatment

2022

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Cancer is a heterogeneous and multifactorial disease that causes high mortality throughout the world; therefore, finding the most effective therapies is a major research challenge. Currently, most anticancer drugs present a limited number of well‐established targets, such as cell proliferation or death; however, it is important to consider that the worse progression of cancer toward pathological stages implies invasion and metastasis processes. Medicinal Inorganic Chemistry (MIC) is a young area that deals with the design, synthesis, characterization, preclinical evaluation, and mechanism of action of new inorganic compounds, called metallodrugs. The properties of metallic ions allow enriching of strategies for the design of new drugs, enabling the adjustment of physicochemical and stereochemical properties. Metallodrugs can adopt geometries, such as tetrahedral, octahedral, square planar, and square planar pyramid, which adjusts their arrangement and facilitates binding with a wide variety of targets. The redox properties of some metal ions can be modulated by the presence of the bound ligands to adjust their interaction, thereby opening a range of mechanisms of action. In this regard, the mechanisms of action that trigger the biological activity of metallodrugs have been generally identified by: (a) coordination of the metal to biomolecules (for instance, cisplatin binds to the N7 in DNA guanine, as Pt‐N via coordination of the inhibition of enzymes); (b) redox‐active; and (c) ROS production. For this reason, a series of metallodrugs can interact with several specific targets in the anti‐invasive processes of cancer and can prevent metastasis. The structural base of several metal compounds shows great anticancer potential by inhibiting the signaling pathways related to cancer progression. In this minireview, we present the advances in the field of antimetastatic effects of metallodrugs.

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Induction of immunogenic cell death in cancer cells by a photoactivated platinum(iv) prodrug

Abstract: Photoactivatable prodrug trans,trans,trans-[Pt(N3)2(OH)2(py)2] has a unique mechanism of action, distinguishing it from other platinum drugs due to its immunomodulating properties, which enhance its anticancer efficacy.

Cited by 48 publications

References 47 publications

Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes

Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes

Metal-based anticancer agents as immunogenic cell death inducers: the past, present, and future

Metallodrugs: an approach against invasion and metastasis in cancer treatment

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