While synthesizing water-soluble amphiphilic phthalocyanines for photodynamic therapy applications is achieved with different substitution patterns (1), it is also of interest to use more hydrophobic derivatives, which then need to be formulated or conjugated to be delivered to cancer cells and tissues. Over the years we have developed several strategies, such as the grafting of photosensitizing phthalocyanines onto biocompatible polymers such as polycaprolactone (2) or poly-L-glutamic acid (3), or their incorporation into silsesquioxane nanoparticles (4). The encapsulation of non-functionalized phthalocyanines into Pluronic-based micelles (5) or other micellar formulations (6) has also been achieved. The design of phthalocyanines’ chemical structures depending the conjugation / encapsulation / formulation will be presented and the different advantages and drawbacks will be discussed.
(1) Synthetic pathways to water-soluble phthalocyanines, Coord. Chem. Rev. 2010, 254, 2792-2847
(2) Aymen Nabeel Yaseen, Atefeh Emami, Haifa Ben Aziza, Merve Dandan Doganci, Ümit İşci, Ayşe Gül Gürek, Erdinc Doganci and Fabienne Dumoulin, J. Porphyrins Phthalocyanines 2024; 28: 107–113.
(3) Lik Voon Kiew, Hoay Yan Cheah, Siew Hui Voon, Elena Gallon, Julie Movellan, Kia Hui Ng, Serkan Alpugan, Hong Boon Lee, Fabienne Dumoulin*, María J. Vicent*, Lip Yong Chung*, Nanomedicine: Nanotechnology, Biology, and Medicine 2017, 13, 1447-1458.
(4) Gülçin Ekineker, Christophe Nguyen, Sumeyra Bayir, Sofia Dominguez-Gil, Umit Isci, Morgane Daurat, Anastasia Godefroy, Laurence Raehm, Clarence Charnay, Erwan Oliviero, Vefa Ahsen, Magali Gary-Bobo*, Jean-Olivier Durand and Fabienne Dumoulin*, Chem. Commun. 2019, 55, 11619-11622
(5) Barbara Pucelik, Ilke Gürol, Vefa Ahsen, Fabienne Dumoulin, Janusz M. Dąbrowski, Eur. J. Med. Chem. 2016, 124, 284-298
(6) Lea P. Gergely, Çiğdem Yüceel, Ümit İşci, Florentin S. Spadin, Lukas Schneider, Bernhard Spingler, Martin Frenz, Fabienne Dumoulin*, and Martina Vermathen*, Mol. Pharmaceutics 2023, 20, 8, 4165–4183