Dendrimer phthalocyanine-encapsulated polymeric micelle-mediated photochemical internalization extends the efficacy of photodynamic therapy and overcomes drug-resistance in vivo


    loading  Checking for direct PDF access through Ovid

Abstract

Clinically, the efficacy of chemotherapeutic agents can be dramatically reduced in cancer cells with multiple drug resistance (MDR). In doxorubicin-resistant breast cancer cells, drugs accumulate only within discrete cytosolic organelles that abrogate their therapeutic effects in vitro and in vivo. Photochemical internalization (PCI), a specific branch of photodynamic therapy (PDT), is a novel strategy utilized for the site-specific triggered drug/gene release. The objective of this study was to evaluate the nanoparticle-based PDT/PCI effects on the reversal of drug resistance. Dendrimer phthalocyanine-encapsulated polymeric micelle (DPc/m)-mediated PCI, combined with doxorubicin, was studied in drug-resistant MCF-7 cells and a xenograft model. Our results show that the internalized DPc/m showed unique PCI properties inside the cells and thereby facilitating doxorubicin release from the endo-lysosomes to nuclei after photoirradiation. Moreover, ‘light before’ PCI showed the highest antitumor efficacy and the depth of the proliferating cell nuclear antigen-negative area in tumor sections after DPc/m-mediated PDT was obviously increased by combination therapy with doxorubicin; this indicates the limitation of depth of light penetration in PDT, which may be improved by PCI. We conclude that nanotechnology-based PCI possesses several clinical benefits, such as overcoming drug resistance and treating deeper lesions that are intractable by PDT alone.Graphical abstract

    loading  Loading Related Articles