DataVXAdvanced Functional MaterialsPaper
journal article·2017-11

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

Tomás Bauleth‐Ramos, Mohammad‐Ali Shahbazi, Dongfei Liu, Flavia Fontana, Alexandra Correia, Patrícia Figueiredo, Hongbo Zhang, João Pedro Martins, Jouni T. Hirvonen, Pedro Granja, Bruno Sarmento, Hélder A. Santos

Advanced Functional Materials· Volume 27· Issue 42
Publisher page
Source abstract

Abstract

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.
Source: crossref · Quality: baseline

Research context

PolymersNanomaterials

OpenAlex topics: RNA Interference and Gene Delivery · Immunotherapy and Immune Responses · Advanced Drug Delivery Systems

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Drug Research Program Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki FI‐00014 Helsinki Finland

Instituto de Investigação e Inovação em Saúde (I3S) University of Porto Rua Alfredo Allen, 208 4200‐135 Porto Portugal

Instituto de Engenharia Biomédica (INEB) University of Porto Rua Alfredo Allen, 208 4200‐135 Porto Portugal

Instituto Ciências Biomédicas Abel Salazar (ICBAS) University of Porto Rua Jorge Viterbo 228 4150‐180 Porto Portugal

Department of Micro‐ and Nanotechnology Technical University of Denmark Ørsteds Plads DK‐2800 Kgs. Lyngby Denmark

Department of Pharmaceutical Science Åbo Akademi University FI‐20520 Turku Finland

CESPU Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde 4585‐116 Gandra Portugal

Helsinki Institute of Life Science (HiLIFE) University of Helsinki FI‐00014 Helsinki Finland

Funding

Fundação para a Ciência e a Tecnologia · Jane ja Aatos Erkon Säätiö · Terveyden Tutkimuksen Toimikunta · Helsingin Yliopisto · Sigrid Juséliuksen Säätiö · European Research Council

References (70)

Show source-provided references
1. 10.1038/nrclinonc.2016.6510.1038/nrclinonc.2016.65 ↗
2. 10.1038/nrc325810.1038/nrc3258 ↗
3. 10.1038/nri217310.1038/nri2173 ↗
4. 10.1016/j.addr.2006.05.00410.1016/j.addr.2006.05.004 ↗
5. 10.1038/nm110010.1038/nm1100 ↗
6. 10.1038/cdd.2013.6710.1038/cdd.2013.67 ↗
7. 10.1111/j.1349-7006.2010.01821.x10.1111/j.1349-7006.2010.01821.x ↗
8. 10.1016/S0959-8049(03)00063-710.1016/S0959-8049(03)00063-7 ↗
9. 10.1126/science.109247210.1126/science.1092472 ↗
10. 10.2174/13816121179522258610.2174/138161211795222586 ↗
11. 10.1186/s40425-015-0053-510.1186/s40425-015-0053-5 ↗
12. 10.1158/1538-7445.AM2017-110.1158/1538-7445.AM2017-1 ↗
13. 10.1016/j.humimm.2012.01.01810.1016/j.humimm.2012.01.018 ↗
14. 10.1007/s00592-013-0476-810.1007/s00592-013-0476-8 ↗
15. 10.1182/blood-2008-12-16400410.1182/blood-2008-12-164004 ↗
16. 10.2217/imt-2016-014110.2217/imt-2016-0141 ↗
17. 10.1021/acs.chemrev.5b0010910.1021/acs.chemrev.5b00109 ↗
18. 10.1038/s41551-017-002910.1038/s41551-017-0029 ↗
19. 10.1021/ja803947s10.1021/ja803947s ↗
20. 10.1016/j.biomaterials.2014.10.07910.1016/j.biomaterials.2014.10.079 ↗
21. 10.1021/mp900311x10.1021/mp900311x ↗
22. 10.1021/mp200378510.1021/mp2003785 ↗
23. 10.1073/pnas.090159210610.1073/pnas.0901592106 ↗
24. 10.1002/adma.20160323910.1002/adma.201603239 ↗
25. 10.1002/adhm.20160140610.1002/adhm.201601406 ↗
26. 10.1021/acs.chemrev.6b0053210.1021/acs.chemrev.6b00532 ↗
27. 10.1021/bc100542r10.1021/bc100542r ↗
28. 10.1081/PDT-12001751710.1081/PDT-120017517 ↗
29. 10.1016/j.cep.2011.05.00610.1016/j.cep.2011.05.006 ↗
30. 10.1016/j.ejps.2009.11.01010.1016/j.ejps.2009.11.010 ↗
31. 10.1371/journal.pone.003292010.1371/journal.pone.0032920 ↗
32. 10.1039/C4CS00487F10.1039/C4CS00487F ↗
33. Oh N. · Int. J. Nanomed. · 2014 · 9 · 51
34. 10.1002/smll.20090115810.1002/smll.200901158 ↗
35. 10.1016/j.jconrel.2006.06.02410.1016/j.jconrel.2006.06.024 ↗
36. 10.1039/C0CS00003E10.1039/C0CS00003E ↗
37. 10.1016/j.biomaterials.2014.05.02010.1016/j.biomaterials.2014.05.020 ↗
38. 10.3389/fonc.2016.0000710.3389/fonc.2016.00007 ↗
39. 10.1038/3504267510.1038/35042675 ↗
40. 10.1371/journal.pone.001858810.1371/journal.pone.0018588 ↗
41. 10.1371/journal.pone.013510110.1371/journal.pone.0135101 ↗
42. 10.1007/s10549-006-9186-z10.1007/s10549-006-9186-z ↗
43. 10.1002/mc.2198510.1002/mc.21985 ↗
44. 10.4049/jimmunol.080352610.4049/jimmunol.0803526 ↗
45. 10.1016/bs.ai.2015.12.00110.1016/bs.ai.2015.12.001 ↗
46. 10.1126/science.768813910.1126/science.7688139 ↗
47. 10.1371/journal.pone.007419810.1371/journal.pone.0074198 ↗
48. 10.1016/j.biomaterials.2014.07.05010.1016/j.biomaterials.2014.07.050 ↗
49. 10.1080/2162402X.2015.111294110.1080/2162402X.2015.1112941 ↗
50. 10.4049/jimmunol.160033910.4049/jimmunol.1600339 ↗
51. 10.1084/jem.2009220310.1084/jem.20092203 ↗
52. 10.1038/sj.cdd.440224710.1038/sj.cdd.4402247 ↗
53. 10.1097/PPO.0b013e3181eb506610.1097/PPO.0b013e3181eb5066 ↗
54. 10.1590/S0100-879X201200750006110.1590/S0100-879X2012007500061 ↗
55. 10.1016/j.molimm.2011.04.01810.1016/j.molimm.2011.04.018 ↗
56. 10.1089/jir.2014.002610.1089/jir.2014.0026 ↗
57. 10.1111/j.1600-065X.2008.00635.x10.1111/j.1600-065X.2008.00635.x ↗
58. 10.3389/fimmu.2011.0003910.3389/fimmu.2011.00039 ↗
59. 10.1146/annurev.immunol.18.1.76710.1146/annurev.immunol.18.1.767 ↗
60. 10.3389/fimmu.2015.0056910.3389/fimmu.2015.00569 ↗
61. 10.1038/nature0552910.1038/nature05529 ↗
62. 10.1073/pnas.090274510610.1073/pnas.0902745106 ↗
63. 10.1084/jem.2012200610.1084/jem.20122006 ↗
64. 10.3389/fimmu.2013.0017710.3389/fimmu.2013.00177 ↗
65. 10.1016/j.cytogfr.2011.10.00110.1016/j.cytogfr.2011.10.001 ↗
66. Mach N. · Cancer Res. · 2000 · 60 · 3239
67. 10.1038/nbt.307110.1038/nbt.3071 ↗
68. 10.1038/ncomms855610.1038/ncomms8556 ↗
69. 10.1002/jcp.104140021910.1002/jcp.1041400219 ↗
70. smart.servier.com published under Creative Commons Attribution License.