Tumor specificity and therapeutic efficacy of photosensitizer-encapsulated glycol chitosan-based nanoparticles in tumor-bearing mice

초록

We reported the development of new nanoscale drug carriers, chitosan-based nanoparticles (CNPs) that can be used for photodynamic therapy. These carriers could encapsulate a photosensitizer, protophorphyrin IX (PpIX), and deliver it to tumor tissue. We already reported that CNPs presented the enhanced tumor target specificity in cancer therapy and imbibed various water insoluble anticancer agents into the hydrophobic multicores of nanoscale particles. In this study, we prepared photosensitizer-encapsulated CNPs by self-assembling amphiphilic glycol chitosan-5 beta-cholanic acid conjugates in an aqueous environment and then encapsulating the water-insoluble photosensitizer (PpIX), with high drug-loading efficiency (>90%) by using a dialysis method. Freshly prepared PpIX-encapsulated CNPs (PpIX-CNPs) had an average diameter of 290 nm and were stable in aqueous solutions for 1 month. As nanoscale drug carriers, PpIX-CNPs exhibited a sustained release profile in vitro and were non-toxic to tumor cells in the dark. In a cell culture system, we observed rapid cellular uptake of the PpIX-CNPs and the released PpIX from CNPs became highly phototoxic upon visible irradiation. In SCC7 tumor-bearing mice, PpIX-CNPs exhibited enhanced tumor specificity and increased therapeutic efficacy compared to free PpIX. Taken together, our results indicate that PpIX-CNPs have potential as an effective drug delivery system for clinical photodynamic therapy. (C) 2009 Elsevier Ltd. All rights reserved.

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