π-π Stacking induced enhanced molecular solubilization, singlet oxygen production, and retention of a photosensitizer loaded in thermosensitive polymeric micelles.
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.
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.
Yang
Y
Shi
Ahmed
A
Elkhabaz
Fjodor A Yousef
FA
Yengej
Joep
J
van den Dikkenberg
Wim E
WE
Hennink
Cornelus F
CF
van Nostrum
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D007211:Indoles / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008823:Micelles; D017646:Organosilicon Compounds / Q000737:chemistry / Q000633:toxicity; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry*; D026082:Singlet Oxygen / Q000378:metabolism*; D013696:Temperature
D000970:Antineoplastic Agents; D007211:Indoles; D008823:Micelles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; C082854:silicon phthalocyanine; D026082:Singlet Oxygen; D011092:Polyethylene Glycols
molecular solubilization; photodynamic therapy; photosensitizers; polymeric micelles; π-π stacking