TY - JOUR
T1 - Directed molecular assembly into a biocompatible photosensitizing nanocomplex for locoregional photodynamic therapy
AU - Lee, Yong Deok
AU - Cho, Hong Jun
AU - Choi, Mi Hwa
AU - Park, Hoyong
AU - Bang, Joona
AU - Lee, Sangyoup
AU - Kwon, Ick Chan
AU - Kim, Sehoon
N1 - Funding Information:
This work was supported by the Program funded by the National Research Foundation of Korea (No. 2014M3A9E5073316 ), BioNano Health-Guard Research Center funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea as Global Frontier Project ( H-GUARD_2014M3A6B2060522 ), and by the Intramural Research Program of KIST ( 2E25270 ).
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/7/10
Y1 - 2015/7/10
N2 - 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.
AB - 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.
KW - Directed molecular assembly
KW - MDA-MB-231 breast cancer cell
KW - Methylene blue
KW - Photodynamic therapy
KW - Polymer nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=84928499399&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2015.04.011
DO - 10.1016/j.jconrel.2015.04.011
M3 - Article
C2 - 25872152
AN - SCOPUS:84928499399
VL - 209
SP - 12
EP - 19
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -