The intracellular uptake of CD95 modified paclitaxel-loaded poly(lactic-co-glycolic acid) microparticles.

Autor: Ateh DD; Pathology Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, 4 Newark Street, London E1 2AT, UK. d.d.ateh@qmul.ac.uk, Leinster VH, Lambert SR, Shah A, Khan A, Walklin HJ, Johnstone JV, Ibrahim NI, Kadam MM, Malik Z, Gironès M, Veldhuis GJ, Warnes G, Marino S, McNeish IA, Martin JE
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2011 Nov; Vol. 32 (33), pp. 8538-47. Date of Electronic Publication: 2011 Aug 06.
DOI: 10.1016/j.biomaterials.2011.07.060
Abstrakt: The CD95/CD95L receptor-ligand system is mainly recognised in the induction of apoptosis. However, it has also been shown that CD95L is over-expressed in many cancer types where it modulates immune-evasion and together with its receptor CD95 promotes tumour growth. Here, we show that CD95 surface modification of relatively large microparticles >0.5 μm in diameter, including those made from biodegradable polylactic-co-glycolic acid (PLGA), enhances intracellular uptake by a range of CD95L expressing cells in a process akin to phagocytosis. Using this approach we describe the intracellular uptake of microparticles and agent delivery in neurons, medulloblastoma, breast and ovarian cancer cells in vitro. CD95 modified paclitaxel-loaded PLGA microparticles are shown to be significantly more effective compared to conventional paclitaxel therapy (Taxol) at the same dose in subcutaneous medulloblastoma (∗∗∗P < 0.0001) and orthotopic ovarian cancer xenograft models where a >65-fold reduction in tumour bioluminescence was measured after treatment (∗P = 0.012). This drug delivery platform represents a new way of manipulating the normally advantageous tumour CD95L over-expression towards a therapeutic strategy. CD95 functionalised drug carriers could contribute to the improved function of cytotoxics in cancer, potentially increasing drug targeting and efficacy whilst reducing toxicity.
(Copyright © 2011 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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