Journal
JOURNAL OF CONTROLLED RELEASE
Volume 155, Issue 3, Pages 458-464Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.06.005
Keywords
Polyion complex micelle; Photosensitizer; Photochemical internalization; Doxorubicin; Drug resistance
Funding
- Department of Health of the Republic of China [DOH99-TD-I-111-TM028]
- Grants-in-Aid for Scientific Research [23350049] Funding Source: KAKEN
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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. (C) 2011 Elsevier B.V. All rights reserved.
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