One-Step Nanoengineering of Hydrophobic Photosensitive Drugs for the Photodynamic Therapy

Nanoengineering of anticancer therapeutic drugs including photosensitizers is highly desired and extremely required for improved therapeutic efficacy. It remains a formidable challenge to achieve nanostructured colloidal particles directly starting from hydrophobic drugs due to their hydrophobic nature and ready aggregation in aqueous ambient. In this work, we report a facile method for a onepot preparation of hydrophobic photosensitizer nanoparticles by coating with different types of polyelectrolyte as stabilizing agents. Regardless of negatively or positively charged polyelectrolyte used, including Poly-L-lysine (PLL, MW=15 k–30 k), PLL (MW=30 k–70 k), heparin, and hyaluronic acid (HA), the hydrophobic photosensitizer BDEA (2,5-Bis(4-(diethylamino)benzylidene)cyclopentanone) as a model drug can be readily manipulated into stable and well-dispersed nanoparticles with size of average 120 nm. Stabilization presumably contributes to electrostatic repulsion of the adsorbed polyelectrolyte layer onto nanoparticles. Their anticancer activity against the HeLa cell line shows that the endocytic internalization of these nanosystems is associated with antiproliferative effects after irradiation with visible light. The one-step preparation strategy may be an alternative approach for the design of nano-formulations of hydrophobic photosensitive drugs, presenting a potential for photodynamic antitumor therapy.