Nutlin-3a and Cytokine Co-loaded Spermine-Modified Acetalated Dextran Nanoparticles for Cancer Chemo-Immunotherapy

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Bauleth-Ramos T, Shahbazi MA, Liu DF, Fontana F, Correia A, Figueiredo P, Zhang HB, Martins JP, Hirvonen JT, Granja P, Sarmento B, Santos HA
Publisher: WILEY-V C H VERLAG GMBH
Publication year: 2017
Journal: Advanced Functional Materials
Journal acronym: ADV FUNCT MATER
Volume number: 27
Issue number: 42
Number of pages: 14
ISSN: 1616-301X


Abstract

The combination of chemo- and immunotherapy represents one promising strategy to overcome the existent challenges in the present-day anticancer therapy. Here, spermine-modified acetalated dextran nanoparticles (Sp-AcDEX NPs), co-loaded with the non-genotoxic molecule Nutlin-3a (Nut3a), and the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), are developed to induce cancer cell death and create a specific antitumor immune response. These polymeric NPs release Nut3a in a pH dependent fashion and induce endosomal escape. Due to Nut3a, the loaded NPs exert specific toxicity toward wild-type p53 cancer cells while avoiding toxicity in immune cells. Furthermore, the NPs show intrinsic immune adjuvancy on monocyte derived-dendritic cells, upregulating the expression of cell surface CD83 and CD86 costimulatory markers. Finally, it is examined that by inducing MCF-7 breast cancer cell death and acting as immune adjuvants, the NPs can downregulate the expression of IL-10 and upregulate IL-1 beta, leading to proliferation of CD3(+) and cytotoxic CD8(+) T cells. Overall, the study suggests that Sp-AcDEX NPs loaded with Nut3a and GM-CSF is a promising system for chemo-immunotherapy, capable of inducing tumor cell death and stimulating immune response.


Keywords

acetalated dextran nanoparticles, chemo-immunotherapy, DENDRITIC CELLS, Nutlin-3a, T-cell activation


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Last updated on 2019-19-09 at 08:34