Directed molecular assembly into a biocompatible photosensitizing nanocomplex for locoregional photodynamic therapy

Yong Deok Lee, Hong Jun Cho, Mi Hwa Choi, Hoyong Park, Joona Bang, Sangyoup Lee, Ick Chan Kwon, Sehoon Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)12-19
Number of pages8
JournalJournal of Controlled Release
Volume209
DOIs
Publication statusPublished - 2015 Jul 10

Keywords

  • Directed molecular assembly
  • MDA-MB-231 breast cancer cell
  • Methylene blue
  • Photodynamic therapy
  • Polymer nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science

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