title: Near-infrared activatable phthalocyanine-poly-L-glutamic acid conjugate: increased cellular uptake and light-dark toxicity ratio toward an effective photodynamic cancer therapy.
abstract: In photodynamic therapy (PDT), the low absorptivity of photosensitizers in an aqueous environment reduces singlet oxygen generation efficiency and thereby decreases photosensitizing efficacy in biological conditions. To circumvent this problem, we designed a phthalocyanine-poly-L-glutamic acid conjugate (1-PG) made from a new phthalocyanine (Pc 1) monofunctionalized to allow adequate conjugation to PGA. The resulting 1-PG conjugate retained high absorptivity in the near-infrared (NIR) region at its λmax675nm in an aqueous environment. The 1-PG conjugate demonstrated good singlet oxygen generation efficiency, increased uptake by 4 T1 breast cancer cells via clathrin-mediated endocytosis, and enhanced photocytotoxic efficacy. The conjugate also displayed a high light-dark toxicity ratio, approximately 1.5-fold greater than zinc phthalocyanine at higher concentration (10 μM), an important feature for the reduction of dark toxicity and unwanted side effects. These results suggest that the 1-PG conjugate could be a useful alternative for deep tissue treatment with enhanced anti-cancer (PDT) efficacy.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lik Voon
authors.initials: LV
authors.lastname: Kiew
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hoay Yan
authors.initials: HY
authors.lastname: Cheah
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Siew Hui
authors.initials: SH
authors.lastname: Voon
authors.affiliation: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Av. Eduardo Primo Yúfera 3, Valencia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gallon
authors.affiliation: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Av. Eduardo Primo Yúfera 3, Valencia, Spain.
authors.forename: Julie
authors.initials: J
authors.lastname: Movellan
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kia Hui
authors.initials: KH
authors.lastname: Ng
authors.affiliation: Department of Chemistry, Gebze Technical University, P.O Box 141, Gebze, Kocaeli, Turkey.
authors.forename: Serkan
authors.initials: S
authors.lastname: Alpugan
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hong Boon
authors.initials: HB
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Gebze Technical University, P.O Box 141, Gebze, Kocaeli, Turkey. Electronic address: fdumoulin@gtu.edu.tr.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dumoulin
authors.affiliation: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Av. Eduardo Primo Yúfera 3, Valencia, Spain. Electronic address: mjvicent@cipf.es.
authors.forename: María J
authors.initials: MJ
authors.lastname: Vicent
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: chungly@hotmail.com.
authors.forename: Lip Yong
authors.initials: LY
authors.lastname: Chung
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004705:Endocytosis; D018698:Glutamic Acid / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D008027:Light; D051379:Mice; D015394:Molecular Structure; D058726:Nanoconjugates / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry
chemical_list: D007211:Indoles; D054833:Isoindoles; D058726:Nanoconjugates; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D018698:Glutamic Acid; C013647:phthalocyanine
keywords: Nano-structure; Near-infrared; Photodynamic therapy; Photosensitizer; Phthalocyanine; Poly-L-glutamic acid