Human serum albumin nanoparticles loaded with phthalocyanine dyes for potential use in photodynamic therapy for atherosclerotic plaques

摘要

Diseases caused by obstruction or rupture of vulnerable plaques in the arterial walls such as cardiovascular infarction or stroke are the leading cause of death in the world. In the present work, we developed human serum albumin nanoparticles loaded by physisorption with zinc phthalocyanine, TT1, mainly used for industrial application as near-infrared photosensitizer and compared these to HSA NPs loaded with the well-known silicone phthalocyanine (Pc4). The use of NIR light allows for better tissue penetration, while the use of nanoparticles permits high local concentrations. The particles were characterized and tested for toxicity and stability as well as for their potential use as a contrast agent and NIR photosensitizer for photodynamic therapy in cardiovascular disease. We focused on the distribution of the nanoparticles in RAW264.7 macrophage cells and atherosclerotic mice. The nanoparticles had an average size of 120 nm according to dynamic light scattering, good loading capacity for zinc phthalocyanine, and satisfying stability in 50% (v/v) fetal bovine serum for 8 hours and in an aqueous environment at 4°C for 4–6 weeks. Under light irradiation we found a high production of singlet oxygen and the products showed no dark toxicity in vitro with macrophages (the target cells in vulnerable plaques), but at a low microgram/mL nanoparticle concentration killed efficiently the macrophages upon LED illumination. Injection of the contrast agent in atherosclerotic mice led to a visible fluorescence signal of zinc phthalocyanine in the atherosclerotic plaque at 30 minutes and in the lungs with a fast clearance of the nanoparticles. Zinc phthalocyanine loaded human serum albumin nanoparticles present an interesting candidate for the visualization and potentially photodynamic treatment of macrophages in arteriosclerotic plaques.