Red light active Pt(iv)–BODIPY prodrug as a mitochondria and endoplasmic reticulum targeted chemo-PDT agent

Abstract

A cisplatin-based platinum(IV) prodrug, [Pt(NH3)2Cl2(OH)(L1)], having L1 as red-light active boron-dipyrromethene (BODIPY) pendant, was synthesized, characterized and its application as a chemo-cum-photodynamic therapy agent studied. Me-L1 as the ligand precursor...

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

“…Here, the BODIPY acts as a photo-activator to initiate the metal reduction process. 29 Red light photo exposure ensured complete reduction within 15 min. The half-life for the complex ( t 1/2 ) upon red-light exposure was observed as 7.5 min (Fig.…”

“…We earlier reported a red-light-active Pt( iv )-BODIPY prodrug showing photocytotoxicity in the PDT window. 29 However, the non-targeting nature of that complex resulted in unwanted photocytotoxicity in normal cells. In continuation of that work to develop a more effective PACT-cum-PDT agent tethered with a targeting moiety, herein, we present the synthesis, characterization and biological properties of a Pt( iv ) prodrug cis , cis , trans -[Pt(NH 3 ) 2 Cl 2 (biotin)( L )] ( 1 ) derived from a cisplatin core, which was initially converted to cis , cis , trans -[Pt(NH 3 ) 2 Cl 2 (OH) 2 ] as the precursor followed by the axial ligation of a red-light active BODIPY ligand H L and biotin (hexahydro-2-oxo-1 H -thieno(3,4- d )imidazole-4-pentanoic acid) as the other axial ligand (PACT, photoactivated chemotherapy).…”

Recent Advances in Light-Controlled Activation of Pt(IV) Prodrugs

“…In a subsequent report, Bera et al used the same approach to functionalize cisplatin with red-light absorbing bodipy moiety [ 66 ]. Log p value 0.06 of the Pt(IV) prodrug 28 was considered optimal for accumulation in mitochondria and endoplasmic reticulum (ER).…”

A Platinum(II) Boron‐dipyrromethene Complex for Cellular Imaging and Mitochondria‐targeted Photodynamic Therapy in Red Light

“…In that respect, photodynamic therapy (PDT) has emerged as a new combination methodology to treat cancer in the presence of a suitable photosensitizer (PS) appended to a potent chemotherapeutic drug candidate that can be activated by light in the presence of molecular oxygen ( 3 O 2 ) to generate singlet oxygen ( 1 O 2 ) as the reactive oxygen species (ROS). [11][12][13][14][15][16] PDT involves the activation of an apparently inactive drug precursor to generate singlet oxygen (as ROS) only on light exposure following its administration or localization at the desired cancer/diseased cell target. The in situ generated singlet oxygen by a type-II photo-process can lead to cellular apoptosis directly or induce tumor vasculature shutdown.…”

“…Therefore, introducing light into cancer therapy provides a new avenue to anticancer drug design to circumvent the problems associated with the conventional drugs belonging to the “platin” family. In that respect, photodynamic therapy (PDT) has emerged as a new combination methodology to treat cancer in the presence of a suitable photosensitizer (PS) appended to a potent chemotherapeutic drug candidate that can be activated by light in the presence of molecular oxygen ( 3 O 2 ) to generate singlet oxygen ( 1 O 2 ) as the reactive oxygen species (ROS) [11–16] …”