Format

Send to

Choose Destination
Adv Healthc Mater. 2014 Dec;3(12):2023-31. doi: 10.1002/adhm.201400455. Epub 2014 Nov 11.

π-π Stacking induced enhanced molecular solubilization, singlet oxygen production, and retention of a photosensitizer loaded in thermosensitive polymeric micelles.

Author information

1
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99 P.O. Box 80082, 3508, TB, Utrecht, The Netherlands; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China.

Abstract

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.

KEYWORDS:

molecular solubilization; photodynamic therapy; photosensitizers; polymeric micelles; π-π stacking

PMID:
25388924
DOI:
10.1002/adhm.201400455
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center