Micellar formulation of indocyanine green for phototherapy of melanoma.
Phototherapy (PT), a light activated treatment modality, is a potential therapeutic option for the treatment of melanoma. In spite of the excellent safety profile and absorption in the near infrared (NIR) range, clinical potential of indocyanine green (ICG) as PT is limited by its short half-life and inefficient tumor accumulation. In this study, we have covalently conjugated ICG-NH2 to the pendant carboxyl groups of poly (ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate) (PEG-PCC) copolymer using carbodiimide coupling, which self-assembled into micelles with a particle size of 30-50 nm and high ICG loading. These ICG conjugated micelles exhibited significant in vitro photodynamic cytotoxicity. Use of sodium azide and NIR radiate on at 4 °C revealed photodynamic and photothermal as mechanism of cytotoxicity of ICG solution and ICG conjugated micelles, respectively. In vivo NIR imaging demonstrated that ICG conjugated micelles prolonged its circulation and increased tumor accumulation through enhanced permeability and retention (EPR) effect. Enhanced tumor accumulation improved therapeutic efficacy with complete tumor regression in NIR irradiated ICG conjugated micelles compared to ICG solution and control in a A375 human melanoma tumor model in athymic nude mice. These results suggest that ICG conjugated micelles can be potentially utilized for PT and imaging of melanoma.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Vaibhav
V
Mundra
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Yang
Y
Peng
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Sandeep
S
Rana
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Amarnath
A
Natarajan
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: ram.mahato@unmc.edu.
Ram I
RI
Mahato
D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry*; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008823:Micelles; D010789:Phototherapy
D008823:Micelles; D007208:Indocyanine Green
Cellular uptake; Indocyanine green; Micelles; Photodynamic therapy; Phototherapy