Supramolecular Photoactivatable Anticancer Hydrogels

• Published in: Journal of the American Chemical Society Vol. 139; no. 16; pp. 5656 - 5659
• Main Authors: Venkatesh, V, Mishra, Narendra Kumar, Romero-Canelón, Isolda, Vernooij, Robbin R, Shi, Huayun, Coverdale, James P. C, Habtemariam, Abraha, Verma, Sandeep, Sadler, Peter J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 26.04.2017
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Borates - chemistry; Borates - pharmacology; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Cisplatin - chemistry; Cisplatin - pharmacology; Dopamine - chemistry; Dopamine - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Fibroblasts - drug effects; Humans; Hydrogels - chemistry; Hydrogels - pharmacology; Macromolecular Substances - chemistry; Macromolecular Substances - pharmacology; Molecular Structure; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology; Particle Size; Photochemical Processes; Structure-Activity Relationship; Surface Properties
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.7b00186

A photoactivatable dopamine-conjugated platinum­(IV) anticancer complex (Pt-DA) has been incorporated into G-quadruplex G4K+ borate hydrogels by using borate ester linkages (Pt-G 4 K + B hydrogel). These were characterized by 11B NMR, attenuated total reflection Fourier transform infrared spectroscopy, circular dichroism, scanning electron microscopy and transmission electron microscopy. Microscopy investigations revealed the transformation of an extended fiber assembly into discrete flakes after incorporation of Pt-DA. Pt-DA showed photocytotoxicity against cisplatin-resistant A2780Cis human ovarian cancer cells (IC50 74 μM, blue light) with a photocytotoxic index <2, whereas Pt-G 4 K + B hydrogels exhibited more potent photocytotoxicity (IC50 3 μM, blue light) with a photocytotoxic index >5. Most notably, Pt-DA and Pt-G 4 K + B hydrogels show selective phototoxicity for cancer cells versus normal fibroblast cells (MRC5).