Development of Biocompatible Photosensitizing Nanocomplex for Photodynamic Therapy Against Retinoblastoma After Intravitreous Injection

Abstract

Purpose : To investigate the therapeutic potential of the biocompatible photosensitizing nanocomplex for photodynamic therapy against retinoblastoma after intravitreous injection.

Methods : The degree of diffusion of the nanocomplex was evaluated in phosphate-buffered saline and porcine vitreous. Fluorescence-activated cell sorting and immunofluorescence analyses provided the data on the degree of endocytosis of the nanocomplex into retinoblastoma cells, Y79, WERI-Rb1, and SNUOT-Rb1. The cytotoxic potential of the nanocomplex was estimated using cell viability assays after the treatment of the nanocomplex and the following laser irradiation. Two weeks after the injection of retinoblastoma cells into the vitreous cavity of Balb/c nude mice to form orthotopic transplantation models, the degree of in vivo endocytosis of the nanocomplex was evaluated by the observation of tumor sections under a fluorescence microscope. The same orthotopic transplantation models were also employed to demonstrate in vivo therapeutic efficacy of the photodynamic therapy after intravitreous injection of the nanocomplex.

Results : The photosensitizing nanocomplex was formed with self-assembly of a photosensitizer and a biocompatible surfactant. In contrast to free methylene blue, which poorly penetrates to tumor cells, the nanocomplexed methylene blue demonstrated effective penetration to retinoblastoma cells. Also, further laser irradiation induced cytotoxicity of retinoblastoma cells after treatment with the nanocomplexed methylene blue. In vivo experiments using an orthotopic transplantation mouse model showed that this photosensitizing nanocomplex penetrated well-formed in vivo tumors after intravitreous injection. Furthermore, photodynamic therapy based on this nanocomplex decreased the degree of tumor formation in the vitreous of mice.

Conclusions : We expect that this photosensitizing nanocomplex based on biocompatible materials can expand the use of photosensitizing materials and photodynamic therapy in the treatment of retinoblastoma.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Diffusion of the photosensitizing nanocomplex in phosphate-buffered saline (PBS) and porcine vitreous. min, minute(s); h, hour(s).

 

Therapeutic efficacy of the photodynamic therapy using the photosensitizing nanocomplex on in vivo tumor formation in orthotopic transplantation models of retinoblastoma.