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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: 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
Förläggare: WILEY-V C H VERLAG GMBH
Publiceringsår: 2017
Tidskrift: Advanced Functional Materials
Tidskriftsakronym: ADV FUNCT MATER
Volym: 27
Nummer: 42
Antal sidor: 14
ISSN: 1616-301X


Abstrakt

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.


Nyckelord

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


Dokument


Senast uppdaterad 2019-14-10 vid 05:34