Photodynamic Therapy of Ovarian Carcinoma Cells with Curcumin-Loaded Biodegradable Polymeric Nanoparticles

载姜黄素的可生物降解聚合物纳米粒子对卵巢癌细胞进行光动力治疗

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作者:Lili Duse, Michael Rene Agel, Shashank Reddy Pinnapireddy, Jens Schäfer, Mohammed A Selo, Carsten Ehrhardt, Udo Bakowsky

Abstract

Accumulation of photosensitisers in photodynamic therapy in healthy tissues is often the cause of unwanted side effects. Using nanoparticles, improved bioavailability and site-specific drug uptake can be achieved. In this study, curcumin, a natural product with anticancer properties, albeit with poor aqueous solubility, was encapsulated in biodegradable polymeric poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CUR-NP). Dynamic light scattering, laser Doppler anemometry and atomic force microscopy were used to characterise the formulations. Using haemolysis, serum stability and activated partial thromboplastin time tests, the biocompatibility of CUR-NP was assessed. Particle uptake and accumulation were determined by confocal laser scanning microscopy. Therapeutic efficacy of the formulation was tested in SK-OV-3 human ovarian adenocarcinoma cells post low level LED irradiation by determining the generation of reactive oxygen species and cytotoxicity. Pharmacologic inhibitors of cellular uptake pathways were used to identify the particle uptake mechanism. CUR-NP exhibited better physicochemical properties such as stability in the presence of light and improved serum stability compared to free curcumin. In addition, the novel nanoformulation facilitated the use of higher amounts of curcumin and showed strong apoptotic effects on tumour cells.

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