A New Photosensitized Oxidation-Responsive Nanoplatform for Controlled Drug Release and Photodynamic Cancer Therapy

Abstract

Abnormal biochemical alteration such as unbalanced reactive oxygen species (ROS) levels has been considered as a potential disease-specific trigger to deliver therapeutics to target sites. However, in view of their minute variations in concentration, short lifetimes, and limited ranges of action, in situ generation of ROS with specific manipulations should be more effective for ROS-responsive drug delivery. Here we present a new delivery nanoplatform for photodynamic therapy (PDT) with on-demand drug release regulated by light irradiation. Rose bengal (RB) molecules, which exhibit a high yield of ROS generation, were encapsulated in a mixture of chitosan (CTS), poly(vinyl alcohol) (PVA), and branched polyethylenimine ( bPEI) with hydrophobic iron oxide nanoparticles through an oil-in-water emulsion method. The as-prepared magnetic nanoclusters (MNCs) with a tripolymer coating displayed high water dispersibility, efficient cellular uptake, and the cationic groups of CTS and bPEI were effective for RB loading through electrostatic interaction. The encapsulation efficiency of RB in MNCs could be further improved by increasing the amount of short bPEI chains. During the photodynamic process, controlled release of the host molecules (i.e., RB) or guest molecules (i.e., paclitaxel) from the bPEI-based nanoplatform was achieved simultaneously through a photooxidation action sensitized by RB. This approach promises specific payload release and highly effective PDT or PDT combined therapy in various cancer cell lines including breast (MCF-7 and multidrug resistant MCF-7 subline), SKOV-3 ovarian, and Tramp-C1 prostate. In in vivo xenograft studies, the nanoengineered light-switchable carrier also greatly augments its PDT efficacy against multidrug resistant MCF-7/MDR tumor as compared with free drugs. All the above findings suggest that the substantial effects of enhanced drug distribution for efficient cancer therapy was achieved with this smart nanocarrier capable of on demand drug release and delivery, thus exerting its therapeutic activity to a greater extent.

Keywords: Controlled drug release; Multidrug resistance; Photodynamic therapy; Photosensitized oxidation; Stimuli-responsive polymer.