Abstract

Retinoblastoma is a rare cancer triggered by genetic mutation that forms in the eyes of children. In industrialized countries, 95% of patients are cured by chemotherapy and conservative treatments. However these treatments can increase the risk of secondary tumors in patients with a constitutional alteration of the retinoblastoma gene Rb1. Photodynamic therapy (PDT) represents a therapeutic approach and may reduce the incidence of secondary tumors. PDT is an established cancer treatment based on the light activation of a photosensitizing agent thus generating cytotoxic reactive oxygen species that cause cellular damage. We focused on mesoporous silica nanoparticles (MSN) for one-photon excited PDT combined with drug delivery and carbohydrate targeting applied on retinoblastoma. We demonstrated that bitherapy (camptothecin delivery and PDT) performed with MSN was efficient in inducing retinoblastoma cell death. Alternatively, MSN designed for two-photon excited PDT were also studied and irradiation in near-infrared at low fluency efficiently killed retinoblastoma cancer cells. These data provide new evidences of the potential of functionalized and targeted MSN for treatment of retinoblastoma and could lead to propose a non-invasive therapy with reduced side effects.

Highlights

  • Retinoblastoma is the most common intraocular malignant tumor in childhood with an incidence of 1 for 20,000 births which occurs during the first five years of life

  • We focused on mesoporous silica nanoparticles (MSN) for one-photon excited Photodynamic therapy (PDT) combined with drug delivery and carbohydrate targeting applied on retinoblastoma

  • We demonstrated that bitherapy performed with MSN was efficient in inducing retinoblastoma cell death

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Summary

Introduction

Retinoblastoma is the most common intraocular malignant tumor in childhood with an incidence of 1 for 20,000 births which occurs during the first five years of life. When tumor is exclusively localize into the eye, the majority of patients can be cured by therapeutic treatments including enucleation or conservative treatments using, intravenous and/or intraarterial chemotherapy [4,5], cryotherapy [6], local thermotherapy or brachytherapy. The potential risks of late effects associated with chemotherapy and carboplatin include increased risk of second cancer, as well as short-term important side effects. Due to the lack of blood supply to vitreous seeding, chemotherapy drugs could not reach the vitreous body through blood-retinal barrier. This is one of the important limiting factors which triggered intravenous chemotherapy as a new injection technique for vitreous disease in retinoblastoma [7]

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