Document details
Nutlin-3a and Cytokine Co-loaded Spermine-Modified Acetalated Dextran Nanoparticles for Cancer Chemo-Immunotherapy(Article)
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- aDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland
- bInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal
- cInstituto de Engenharia Biomédica (INEB), University of Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal
- dInstituto Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo 228, Porto, 4150-180, Portugal
- eDepartment of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads, Kgs. Lyngby, DK-2800, Denmark
- fDepartment of Pharmaceutical Science, Åbo Akademi University, Turku, FI-20520, Finland
- gCESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, 4585-116, Portugal
- hHelsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, FI-00014, Finland
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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-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. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Indexed keywords
| Engineering controlled terms: | Cell deathCell membranesCytologyDextranDiseasesImmune systemMacrophagesNanoparticlesT-cellsToxicity |
|---|---|
| Engineering uncontrolled terms | Anti-cancer therapiesAnti-tumor immuneChemo-immunotherapyDendritic cellsGranulocyte-macrophage colony stimulating factorsMCF-7 breast cancer cellsNutlin-3aT cell activation |
| Engineering main heading: | Cells |
Funding details
| Funding sponsor | Funding number | Acronym |
|---|---|---|
| Seventh Framework Programme | 310892 | |
| Fuel Cell Technologies Program | ||
| Academy of Finland | 252215,297580,281300 | |
| Fundação para a Ciência e a Tecnologia See opportunities | ||
| European Regional Development Fund | ||
| European Research Council | ||
| Ministério da Ciência, Tecnologia e Inovação | POCI-01-0145-FEDER-007274 | |
| 4704010 | ||
| POCI | ||
| 4704580 |
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1
T.B.-R. acknowledges financial support from the Fundação para a Ciência e a Tecnologia (grant no. SFRH/BD/110859/2015). Financial support from the FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through the FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) is acknowledged. Prof. H.Z. acknowledges financial support from the Jane and Aatos Erkko Foundation (decision no. 4704010) and the Academy of Finland (decision no. 297580). Prof. H.A.S. acknowledges financial support from the Academy of Finland (decision no. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, the Sigrid Jusélius Foundation (decision no. 4704580), the Helsinki Institute of Life Science, and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007−2013, grant no. 310892). The authors thank the Electron Microscopy Unit and the Flow Cytometry Unit of the Institute of Biotechnology, University of Helsinki for providing laboratory facilities and assistance with the measurements.
- ISSN: 1616301X
- CODEN: AFMDC
- Source Type: Journal
- Original language: English
- DOI: 10.1002/adfm.201703303
- Document Type: Article
- Publisher: Wiley-VCH Verlag
Shahbazi, M.-A.; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland;
© Copyright 2017 Elsevier B.V., All rights reserved.
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