Platinum complexes as light promoted anticancer agents: a redefined strategy for controlled activation

Abstract

Site-specific delivery and amenable activation of prodrugs are indispensible criteria for designing novel anticancer agents. Platinum based drugs vanguard the chemotherapeutic regimes and over the years significant attention has been paid to achieve more efficacious drugs with fewer adverse effects. The switch from platinum(ii) drugs to the inert platinum(iv) analogues proved advantageous but the new prodrugs still suffered from unspecific cytotoxic actions. Thus the photoactivation of an inert platinum prodrug specifically within neoplastic cells provided the desired spatio-temporal control over drug activation by means of illumination, thereby limiting the cytotoxic events to only at the targeted tumors. This article collates research on platinum complexes which exhibit potential light mediated anticancer effects and provides insights into the underlying mechanisms of activation. Fine tuning of the coordination sphere results in dramatic alteration of the redox and spectral properties of both ground and excited states and the cellular properties of the molecules. This concise article highlights the various light promoted strategies employed to attain a controlled release of active platinum(ii) and/or reactive oxygen species such as photoreduction, photocaging, photodissociation and photosensitization. Such dual action photoactive metal complexes with improved aqueous solubility and versatility are promising candidates for combination therapy which is likely to be the future of anticancer research.

Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin

“…Doxorubicin acts on three different fronts (i) by altering the fluidity of the cell membrane; (ii) by forming free radicals by enzymatic reduction; and finally (iii) by blocking the DNA and RNA synthesis through the reduction the topoisomerase II activity [24, 26]. Cisplatin’s mechanism is related to the selective inhibition of DNA synthesis because of its alkylating activity [27]. 5-fluorouracyl is considered to be a drug belonging to the antimetabolite class capable of chemically blocking DNA synthesis as it is a base analogue.…”

“…The cisplatin, that acts by selective inhibition of DNA synthesis owing to its alkylating activity [27], presented distinct results for 1 and 2, being an antagonist for the former and additive agent for the latter. It is therefore assumed that the alkylating activity can be influenced by sesquiterpene lactones.…”

A Platinum(II) Complex of Heptamethine Cyanine for Photoenhanced Cytotoxicity and Cellular Imaging in Near‐IR Light

“…Recently, there have been a few successful efforts to photo‐release bioactive Pt II species . Carboplatin and its 7‐azaindole based analogues were shown to form bifunctional Pt‐DNA adducts on UVA light exposure ,.…”

“…Based on the precedent of existing platinum(II) photoactivatable complexes, we posited that a diammine‐bound Pt II system having a photodetachable O^O bidentate donor in direct conjugation with the heptamethine cyanine framework would release an active cisplatin on near‐IR light exposure. To realize our hypothesis, we successfully designed a Pt II conjugate of heptamethine cyanine, which we call IR797‐Platin ( 1 ; Figure a).…”

Photoactive platinum(iv) complex conjugated to a cancer-cell-targeting cyclic peptide

“…Photoactive diazido platinum(IV) prodrugs offer potential for improved treatment of cancer due to their high stability and low toxicity in the dark, potent photocytotoxicity, and novel mechanism of action which has the possibility to overcome cisplatin resistance in cancer cells. [1][2][3][4][5][6] Among them, trans,trans, trans-[Pt(N 3 ) 2 (OH) 2 ( py) 2 ] (FM-190) is a promising prodrug candidate, 7 which can be activated by visible light with a high photocytotoxicity index. Derivatisation of the detachable axial ligands in platinum(IV) prodrugs is now a common strategy to enhance their pharmacological properties.…”