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π–π Stacking Induced Enhanced Molecular Solubilization, Singlet Oxygen Production, and Retention of a Photosensitizer Loaded in Thermosensitive Polymeric Micelles
Author(s) -
Shi Yang,
Elkhabaz Ahmed,
Yousef Yengej Fjodor A.,
van den Dikkenberg Joep,
Hennink Wim E.,
van Nostrum Cornelus F.
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201400455
Subject(s) - singlet oxygen , photosensitizer , stacking , micelle , chemistry , photodynamic therapy , phthalocyanine , aromaticity , photochemistry , oxygen , materials science , organic chemistry , aqueous solution , molecule
Cancer photodynamic therapy (PDT) by photosensitizers (PS)‐loaded polymeric micelles (PM) is hampered by the tendency of PS to aggregate in PM and/or by premature release of PS in the blood circulation. In the present study, aromatic thermosensitive PM, characterized by π–π stacking interaction, are used to encapsulate an axially solketal‐substituted silicon phthalocyanine (Si(sol) 2 Pc) with enhanced loading capacity, smaller size, and significantly improved retention of Si(sol) 2 Pc compared with systems based on thermosensitive PM lacking aromatic groups. Interestingly, Si(sol) 2 Pc is much less prone to aggregation in the aromatic PM, i.e., the amount of Si(sol) 2 Pc that could be encapsulated without aggregation is 330 times higher in the aromatic PM than in the nonaromatic PM. Furthermore, Si(sol) 2 Pc in the aromatic PM in a molecularly dissolved (non‐aggregated) form displays three times more efficient singlet oxygen production than Si(sol) 2 Pc aggregated in the non‐aromatic PM. As a result, the photocytotoxicity of Si(sol) 2 Pc‐loaded aromatic PM to B16F10 cells is increased, compared with that of the non‐aromatic PM, while no significant cytotoxicity is observed in the dark. Fluorescence‐activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) analysis shows cell uptake of Si(sol) 2 Pc loaded in the aromatic PM, and the Si(sol) 2 Pc is taken up by the cells together with the micelles. The efficient singlet oxygen production of Si(sol) 2 Pc dissolved in the aromatic PM makes it an interesting formulation for cancer PDT.