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Nutlin‐3a and Cytokine Co‐loaded Spermine‐Modified Acetalated Dextran Nanoparticles for Cancer Chemo‐Immunotherapy
Author(s) -
BaulethRamos Tomás,
Shahbazi MohammadAli,
Liu Dongfei,
Fontana Flavia,
Correia Alexandra,
Figueiredo Patrícia,
Zhang Hongbo,
Martins João Pedro,
Hirvonen Jouni T.,
Granja Pedro,
Sarmento Bruno,
Santos Hélder A.
Publication year - 2017
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201703303
Subject(s) - cancer immunotherapy , immune system , immunotherapy , cytokine , cancer research , materials science , cytotoxic t cell , cancer cell , monocyte , dendritic cell , cd8 , immunogenic cell death , cd86 , t cell , cancer , biology , immunology , biochemistry , in vitro , genetics
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‐1β, 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.