title: Molecular-target-based anticancer photosensitizer: synthesis and in vitro photodynamic activity of erlotinib-zinc(II) phthalocyanine conjugates.
abstract: Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR-overexpressing cancer cells owing to the presence of the small molecular-target-based anticancer agent erlotinib. All conjugates were found to be essentially non-cytotoxic in the absence of light (up to 50 μM), but upon illumination, they show significantly high photo-cytotoxicity toward HepG2 cells, with IC50 values as low as 9.61-91.77 nM under a rather low light dose (λ=670 nm, 1.5 J cm(-2) ). Structure-activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular-target-based photodynamic therapy.
authors.affiliation: Fujian Engineering Research Center for Drugs, Diagnoses and Treatment of Photodynamic Therapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108 (P.R. China).
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Liu
authors.forename: Ming-Dong
authors.initials: MD
authors.lastname: Huang
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Xue
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D015195:Drug Design; D066246:ErbB Receptors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D008027:Light; D008113:Liver Neoplasms / Q000188:drug therapy; D018613:Microscopy, Confocal; D009942:Organometallic Compounds / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011799:Quinazolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D017967:Zinc Compounds
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011799:Quinazolines; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: conjugates; erlotinib; molecular targeting; photodynamic therapy; phthalocyanine