Photodynamic therapy with decacationic [60]fullerene monoadducts: Effect of a light absorbing electron-donor antenna and micellar formulation

• Published in: Nanomedicine Vol. 10; no. 4; pp. 795 - 808
• Main Authors: Yin, Rui, MD, PhD, Wang, Min, PhD, Huang, Ying-Ying, MD, Huang, Huang-Chiao, PhD, Avci, Pinar, MD, Chiang, Long Y., PhD, Hamblin, Michael R., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2014
• Subjects: Apoptosis; Decacationic fullerene monoadducts; Fullerenes - chemistry; Fullerenes - pharmacology; HeLa Cells; Humans; Internal Medicine; Light absorbing antenna; Micelles; Nanomedicine; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Photochemotherapy - methods; Photodynamic therapy; Reactive oxygen species; Structure-function relationship; Reactive oxygen species; Photodynamic therapy; Decacationic fullerene monoadducts; Micelles; Light absorbing antenna; Nanomedicine; Structure-function relationship; Apoptosis
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2013.11.014

Abstract We report the synthesis and anticancer photodynamic properties of two new decacationic fullerene (LC14) and red light-harvesting antenna-fullerene conjugated monoadduct (LC15) derivatives. The antenna of LC15 was attached covalently to C60 > with distance of only < 3.0 Ǻ to facilitate ultrafast intramolecular photoinduced-electron-transfer (for type-I photochemistry) and photon absorption at longer wavelengths. Because LC15 was hydrophobic we compared formulation in Cremophor EL micelles with direct dilution from dimethylacetamide. LC14 produced more1 O2 than LC15, while LC15 produced much more HO · than LC14 as measured by specific fluorescent probes. When delivered by DMA, LC14 killed more HeLa cells than LC15 when excited by UVA light, while LC15 killed more cells when excited by white light consistent with the antenna effect. However LC15 was more effective than LC14 when delivered by micelles regardless of the excitation light. Micellar delivery produced earlier apoptosis and damage to the endoplasmic reticulum as well as to lysosomes and mitochondria. From the Clinical Editor This team of authors report the synthesis and the photodynamic properties of two new derivatives for cancer treatment; one is a decacationic fullerene (LC14) and the other is a red light-harvesting antenna-fullerene conjugated monoadduct (LC15) utilizing a HeLa cell model.