Thursday, April 28, 2016

PolySciTech mPEG-PLLA used for zinc (II) phthalocyanine delivery as part of photodynamic cancer therapy research

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers including mPEG-PLLA. Recently, researchers in Poland used the product PolyVivo AK004 (mPEG-PLLA 2000-5000) to develop a delivery system for zinc(II) phthalocyanine (ZnPc). ZnPc is a photosensitizer which does not have toxicity towards cells unless it is illuminated with a certain wavelength of light (in the range of 600-800nm). Under illumination this one generates unstable singlet oxygen which is a highly cytotoxic agent that kills the cancer cells. The goal with this therapy is that the photosensitizer is applied systemically but only the tumor sites are illuminated by a clinician so that these are selectively targeted. The use of mPEG-PLLA, AK004 reported to have a critical micelle concentration of 2.8 x 10^− 3 mg/mL, led to a greatly increased stability, blood circulation, solubility, and delivery of ZnPc. This exciting research holds promise for cancer therapy. Read more: Lamch, Łukasz, Julita Kulbacka, Jadwiga Pietkiewicz, Joanna Rossowska, Magda Dubińska-Magiera, Anna Choromańska, and Kazimiera A. Wilk. "Preparation and characterization of new zinc (II) phthalocyanine—Containing poly (l-lactide)-b-poly (ethylene glycol) copolymer micelles for photodynamic therapy." Journal of Photochemistry and Photobiology B: Biology 160 (2016): 185-197. http://www.sciencedirect.com/science/article/pii/S1011134416302603

“Abstract: 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. Highlights: 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. Keywords: Nano-photosensitizer; Human melanoma; Phototoxicity; Apoptosis; Biocompatibility”


Post a Comment