Mesoporous Silica Nanoparticles for one and two-photon Photodynamic Therapy

摘要

Covalent attachment of water-soluble monophotonic photosensitizers (Figure 1) into MSN for photodynamic therapy (PDT) applications is described. Those MSN were monodisperse with a diameter of 100 nm, a specific surface area of 860 m~2/g and a pores diameter of 2.2 nm. These MSN were proved to be active on MDA-MB-231 breast cancer cells after endocytosis. Moreover, MSN were functionalized on their surface by mannose using an original pathway with diethyl squarate as the linker. Those mannose-functionalized MSN dramatically improved the efficiency of PDT on breast cancer cells. In addition, the involvement of mannose receptors for the active endocytosis of mannose-functionalized MSN was demonstrated (Figure 2). Furhthermore, PDT combined with two-photon excitation (TPE) in the near infra red (NIR) region offers new perspectives for the ablation of solid tumours due to the increased penetration depth and unique 3D spatial resolution it provides. We present a novel approach based on MSN in which a new two-photon photosensitizer is covalently attached. This photosensitizer has much larger two-photon absorption cross-section (σ_2) than standard ones in the NIR region. In addition, the surface of the MSN is post-functionalized with mannose residues allowing for efficient targeting of lectins over-expressed by cancer cells. These tailored MSN were found to be very active in inducing cancer cell death upon short (typically 3 s) two-photon excitation at 760 nm when incubated with colon (HCT-116), retinoblastoma (Y-79) and breast (MCF-7, MDA-MB-231) cancer cells. These MSN were also tested for in vivo two-photon photodynamic therapy. A 70% regression of tumour size upon single treatment was observed in athymic mice bearing HCT-116 colon tumour xenografts. In addition, this treatment impaired the development of metastases associated with cancer spreading. This therapeutic approach could be particularly suited in the setting of localized small solid tumours whose detection has dramatically increased with routine cancer screening.