Photoinduced Reduction of Novel Dual-Action Riboplatin Pt(IV) Prodrug

Abstract

Controlled photoreduction of Pt­(IV) prodrugs is a challenging task due to the possibility of targeted light-controlled activation of anticancer agents without affecting healthy tissues. Also, a conjugation of photosensitizers and clinically used platinum drugs into one Pt­(IV) prodrug allows combining photodynamic therapy and chemotherapy approaches into one molecule. Herein, we designed the cisplatin-based Pt­(IV) prodrug Riboplatin with tetraacetylriboflavin in the axial position. A novel Pt­(IV) prodrug is able to act both as a photodynamic therapy (PDT) agent through the conversion of ground-state 3O2 to excited-state 1O2 and as an agent of photoactivated chemotherapy (PACT) through releasing of cisplatin under gentle blue light irradiation, without the requirement of a reducing agent. The light-induced behavior of Riboplatin was investigated using an electrochemical sensor in MCF-7 tumor spheroids. Photocontrolled cisplatin release and ROS generation were detected electrochemically in real time. This appears to be the first confirmation of simultaneous photoactivated release of anticancer drug cisplatin and ROS from a dual-action Pt­(IV) prodrug observed from the inside of living tumor spheroids.

Biotin and boron-dipyrromethene-tagged platinum(iv) prodrug for cellular imaging and mito-targeted photocytotoxicity in red light

“…A photo-triggered ligand release with concomitant metal reduction is well known for the Pt( iv ) complex showing photoactivated chemotherapeutic activity. 35,41,42 Light exposure at the wavelength of BODIPY-based π–π* transition results in photo-induced electron transfer from BODIPY to the Pt( iv ) centre. To rationalise this fact, the complex solution in DMSO/DPBS mixture was irradiated with a 642 nm diode laser and the emission spectra were recorded sequentially (Fig.…”

Light-Responsive Pt(IV) Prodrugs with Controlled Photoactivation and Low Dark Toxicity

“…Electrochemical detection of light-induced cisplatin release can be carried out in real time in the irradiated solution; we have previously reported this technique for electrochemical detection of light-induced cisplatin release from the Riboplatin prodrug. 8 In addition, electrochemical detection is insensitive to possible ligand exchange reactions of cisplatin, and thus, light-induced accumulation of cisplatin could be quantified more accurately. 29,30 Platinized nanoelectrode was prepared as described previously (Figure S37 in the SI).…”

“…7 Recently, we reported a cisplatin-based dualaction Pt(IV) prodrug Riboplatin with tetraacetylriboflavin in the axial position, capable of light-induced cisplatin release and reactive oxygen species (ROS) formation. 8 Boron dipyrromethene derivatives (BODIPY) are a large class of organoboron fluorophores with excellent spectroscopic properties, high molar extinction coefficient, and photostability. 9 These properties made possible various applications of BODIPY dyes, such as fluorescent stains, agents of fluorescent imaging, and laser dyes.…”

Riboflavin Crystals with Extremely High Water Solubility

“…14 Riboplatin, a cisplatin-based Pt(IV) prodrug with tetraacetylriboflavin in an axial position, was designed as a tumor-affine molecule with the photoactivated chemo/photodynamic therapy properties. 15 The large-scale synthesis of poorly water-soluble Rf is exclusively accomplished by microbial fermentation without the involvement of chemical synthesis. 16 The main strains for the industrial production of Rf are derived from the bacteria Bacillus subtilis and the fungus Ashbya gossypii, 17 and for highly water-soluble FMN and FAD synthesis, complex biotechnological and chemical processes are necessary.…”

“…An amphiphilic riboflavin derivative was used for targeted drug delivery in liposomal constructs . Riboplatin, a cisplatin-based Pt­(IV) prodrug with tetraacetylriboflavin in an axial position, was designed as a tumor-affine molecule with the photoactivated chemo/photodynamic therapy properties …”