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Nanomedicine. 2017 May;13(4):1447-1458. doi: 10.1016/j.nano.2017.02.002. Epub 2017 Feb 16.

Near-infrared activatable phthalocyanine-poly-L-glutamic acid conjugate: increased cellular uptake and light-dark toxicity ratio toward an effective photodynamic cancer therapy.

Author information

1
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
2
Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Av. Eduardo Primo Yúfera 3, Valencia, Spain.
3
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
4
Department of Chemistry, Gebze Technical University, P.O Box 141, Gebze, Kocaeli, Turkey.
5
Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
6
Department of Chemistry, Gebze Technical University, P.O Box 141, Gebze, Kocaeli, Turkey. Electronic address: fdumoulin@gtu.edu.tr.
7
Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Av. Eduardo Primo Yúfera 3, Valencia, Spain. Electronic address: mjvicent@cipf.es.
8
Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: chungly@hotmail.com.

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 λmax 675nm 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.

KEYWORDS:

Nano-structure; Near-infrared; Photodynamic therapy; Photosensitizer; Phthalocyanine; Poly-L-glutamic acid

PMID:
28214608
DOI:
10.1016/j.nano.2017.02.002
[Indexed for MEDLINE]

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