title: Dendrimer phthalocyanine-encapsulated polymeric micelle-mediated photochemical internalization extends the efficacy of photodynamic therapy and overcomes drug-resistance in vivo.
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.
authors.affiliation: Department of Chemistry, College of Science, National Chung Hsing University, Taiwan.
authors.forename: Hsueh-Lin
authors.initials: HL
authors.lastname: Lu
authors.forename: Wei-Jhe
authors.initials: WJ
authors.lastname: Syu
authors.forename: Nobuhoro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.forename: Ping-Shan
authors.initials: PS
authors.lastname: Lai
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004705:Endocytosis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054833:Isoindoles; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D017319:Photosensitizing Agents; D004317:Doxorubicin; C013647:phthalocyanine