Preparation and characterization of new zinc(II) phthalocyanine — Containing poly(l-lactide)-b-poly(ethylene glycol) copolymer micelles for photodynamic therapy
•We developed novel ZnPc-loaded mPEG-b-PLLA micelles to improve the therapeutic effect of PDT.•Encapsulated ZnPc exhibited much better photostability during irradiation than free photosensitizer.•Polymeric micelles efficiently deliver the photosensitizer in metastatic melanoma cells (Me45).•Encapsulated ZnPc was found to be safe for normal keratinocytes, macrophages and endothelial cells.
Poly(l-lactide)-b-poly(ethylene oxide) block copolymer (mPEG-b-PLLA) micelles were fabricated and applied as a new biodegradable and biocompatible nanocarrier for solubilization of hydrophobic zinc (II) phthalocyanine (ZnPc). The nanocarrier demonstrated a good colloidal stability and its in vitro sustained cargo release profile was assessed. Photobleaching of ZnPc, both in its native form and encapsulated in the obtained polymeric micelles, was studied by means of spectroscopic measurements. The photodynamic reaction (PDR) protocol for cyto- and photocytotoxicity was performed on metastatic melanoma cells (Me45), normal human keratinocytes (HaCaT) being used for comparison. The intracellular accumulation of free and encapsulated ZnPc was visualized at various time periods (1, 3 and 24 h). The proapoptotic potential of the encapsulated phthalocyanine was evaluated by monitoring DNA double strand break damage fragmentation (TUNEL assay) and caspase 3/7 activity. In addition, in vitro biocompatibility studies were conducted by determining hemolytic activity of Zn-Pc-loaded mPEG-b-PLLA micelles and their lack of cytotoxicity against macrophages (P388/D1) and endothelial cells (HUV-EC-C). Our results suggest that the PDR using Zn-Pc-loaded mPEG-b-PLLA micelles can be effective in inhibiting tumor cell growth and apoptosis induction with higher responses, observed for Me45 cells. Additionally, the ZnPc-loaded micelles appear to be hemato-biocompatible and safe for normal keratinocytes, macrophages and endothelial cells.
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Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 160, July 2016, Pages 185–197