Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small‐Molecular‐Target‐Based Photodynamic Therapy

• Published in: ChemMedChem 2017-09, Vol.12 (18), p.1504-1511
• Main Authors: Chen, Juan‐Juan, Huang, Yi‐Zhen, Song, Mei‐Ru, Zhang, Zhi‐Hong, Xue, Jin‐Ping
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; antitumor agents; Cancer; Cell culture; Cell Survival - drug effects; Cell Survival - radiation effects; Conjugates; Culture media; Epidermal growth factor receptors; erlotinib; Erlotinib Hydrochloride - chemistry; Hep G2 Cells; Humans; Indoles - chemistry; Isomerization; Light; Liver Neoplasms - drug therapy; Lysosomes; Microscopy, Confocal; Mitochondria; Organosilicon Compounds - chemistry; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - metabolism; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Phototoxicity; phthalocyanines; Polyethylene glycol; Polyethylene Glycols - chemistry; Reactive Oxygen Species - metabolism; Receptor, Epidermal Growth Factor - metabolism; Silicon; Targeted cancer therapy; targeted imaging; Zinc; Zinc - chemistry
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201700384

Small‐molecular‐target‐based photodynamic therapy—a promising targeted anticancer strategy—was developed by conjugating zinc(II) phthalocyanine with a small‐molecular‐target‐based anticancer drug. To prevent self‐aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di‐substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell‐based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC50 values as low as 8 nm under a light dose of 1.5 J cm−2). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR‐overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity. Good aim: A small‐molecular‐target‐based anticancer drug with a simple chemical structure and high stability was found to be ideal for conjugation with photosensitizers to improve targeting of cancer cells. We developed this “smart” targeted therapeutic strategy and synthesized two silicon phthalocyanine–erlotinib conjugates with good biocompatibility, high tumor selectivity, and anticancer activity for photodynamic therapy.