title: Directed molecular assembly into a biocompatible photosensitizing nanocomplex for locoregional photodynamic therapy.
abstract: Methylene blue (MB), a water-soluble cationic dye widely used in the clinic, is known to photosensitize the generation of cytotoxic singlet oxygen efficiently, and thus, has attracted interest as a potential drug for photodynamic therapy (PDT). However, its use for the in vivo PDT of cancer has been limited due to the inherently poor cell/tissue accumulation and low biological stability in the free molecular form. Here, we report a simple and biocompatible nanocomplex formulation of MB (NanoMB) that is useful for in vivo locoregional cancer treatment by PDT. NanoMB particles were constructed through the self-assembly of clinically usable molecules (MB, fatty acid and a clinically approved polymer surfactant) directed by the dual (electrostatic and hydrophobic) interactions between the ternary constituents. The nanocomplexed MB showed greatly enhanced cell internalization while keeping the photosensitization efficiency as high as free MB, leading to distinctive phototoxicity toward cancer cells. When administered to human breast cancer xenograft mice by peritumoral injection, NanoMB was capable of facile penetration into the tumor followed by cancer cell accumulation, as examined in vivo and histologically with the near-infrared fluorescence signal of MB. The quintuple PDT treatment by a combination of peritumorally injected NanoMB and selective laser irradiation suppressed the tumor volume efficaciously, demonstrating potential of NanoMB-based PDT as a biocompatible and safe method for adjuvant locoregional cancer treatment.
authors: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea; Department of Chemical and Biological Engineering, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, South Korea.
authors: Yong-Deok
authors: YD
authors: Lee
authors: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors: Hong-Jun
authors: HJ
authors: Cho
authors: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors: Mi-Hwa
authors: MH
authors: Choi
authors: Department of Surgery, Kyungpook National University Hospital, Daegu 700-721, South Korea.
authors: Hoyong
authors: H
authors: Park
authors: Department of Chemical and Biological Engineering, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, South Korea.
authors: Joona
authors: J
authors: Bang
authors: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors: Sangyoup
authors: S
authors: Lee
authors: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors: Ick Chan
authors: IC
authors: Kwon
authors: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea. Electronic address: sehoonkim@kist.re.kr.
authors: Sehoon
authors: S
authors: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008027:Light; D008751:Methylene Blue / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019301:Oleic Acid / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D020442:Poloxamer / Q000737:chemistry; D026082:Singlet Oxygen / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D017319:Photosensitizing Agents; D013501:Surface-Active Agents; D020442:Poloxamer; D026082:Singlet Oxygen; D019301:Oleic Acid; C013173:osteum; D008751:Methylene Blue
keywords: Directed molecular assembly; MDA-MB-231 breast cancer cell; Methylene blue; Photodynamic therapy; Polymer nanoparticles