title: Augmented EPR effect by photo-triggered tumor vascular treatment improved therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with low permeable vasculature.
abstract: The effects of photo-triggered tumor vascular treatment (PVT) on the structural and functional properties of tumor vasculature were assessed in Colon-26 (C26) and B16/BL6 (B16) tumor-bearing mice. Furthermore, anti-tumor efficacy of subsequently injected PEG liposomal paclitaxel (PL-PTX) was also evaluated. As a photosensitizer, a hydrophobic porphyrin derivative was used and formulated in polymeric nanoparticle composed of polyethylene glycol-block-polylactic acid to avoid its non-specific in vivo disposition. In the mice bearing C26 with high permeable vasculature, the prominent anti-tumor activity was confirmed by PVT alone, but the subsequently injected PL-PTX did not show any additive effect. PVT itself initially induced apoptotic cell death of tumor vascular endothelial cells and platelet aggregation, which would have subsequently induced apoptosis of C26 tumor cells surrounding the vasculature. On the other hand, in the mice bearing B16 with low permeable vasculature, PVT enhanced the anti-tumor activity of subsequently injected PL-PTX, which would be attributed to the tumor disposition amount and area of PEG liposomes enhanced by PVT. These results clearly indicated that the treatment would have made it possible to provide more efficient extravasation of PL-PTX, leading to its more potent anti-tumor effect.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Araki
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ogawara
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kawai
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, Japan.
authors.forename: Taka-ichi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ono
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan. Electronic address: higaki@pharm.okayama-u.ac.jp.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D008027:Light; D008081:Liposomes; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D017239:Paclitaxel; C041104:dimethyl protoporphyrin IX
keywords: Cancer chemotherapy; Endothelial cell; Liposome; Photodynamic treatment; Vascular permeability