PMID- 28557249 OWN - NLM STAT- MEDLINE DCOM- 20180321 LR - 20180321 IS - 2192-2659 (Electronic) IS - 2192-2640 (Linking) VI - 6 IP - 13 DP - 2017 Jul TI - Dendritic Mesoporous Silica Nanoparticles for pH-Stimuli-Responsive Drug Delivery of TNF-Alpha. LID - 10.1002/adhm.201700012 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic immune stimulatory cytokine and natural endotoxin that can induce necrosis and regression in solid tumors. However, systemic administration of TNF-alpha is not feasible due to its short half-life and acute toxicity, preventing its widespread use in cancer treatment. Dendritic mesoporous silica nanoparticles (DMSN) are used coated with a pH-responsive block copolymer gate system combining charged hyperbranched polyethylenimine and nonionic hydrophilic polyethylenglycol to encapsulate TNF-alpha and deliver it into various cancer cell lines and dendritic cells. Half-maximal effective concentration (EC(50) ) for loaded TNF-alpha is reduced by more than two orders of magnitude. Particle stability and premature cargo release are assessed with enzyme-linked immunosorbent assay. TNF-alpha-loaded particles are stable for up to 5 d in medium. Tumor cells are grown in vitro as 3D fluorescent ubiquitination-based cell cycle indicator spheroids that mimic in vivo tumor architecture and microenvironment, allowing real-time cell cycle imaging. DMSN penetrate these spheroids, release TNF-alpha from its pores, preferentially affect cells in S/G2/M phase, and induce cell death in a time- and dose-dependent manner. In conclusion, DMSN encapsulation is demonstrated, which is a promising approach to enhance delivery and efficacy of antitumor drugs, while minimizing adverse side effects. CI - (c) 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Kienzle, Arne AU - Kienzle A AUID- ORCID: 0000-0002-4556-2993 AD - Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1,, 55131, Mainz, Germany. AD - Laboratory of Adaptive and Regenerative Biology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA. AD - The University of Queensland, The University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Brisbane, QLD, 4102, Australia. FAU - Kurch, Sven AU - Kurch S AD - Institute for Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14,, 55128, Mainz, Germany. FAU - Schloder, Janine AU - Schloder J AD - Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1,, 55131, Mainz, Germany. FAU - Berges, Carsten AU - Berges C AD - Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1,, 55131, Mainz, Germany. FAU - Ose, Robert AU - Ose R AD - Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1,, 55131, Mainz, Germany. FAU - Schupp, Jonathan AU - Schupp J AD - Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1,, 55131, Mainz, Germany. FAU - Tuettenberg, Andrea AU - Tuettenberg A AD - Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1,, 55131, Mainz, Germany. FAU - Weiss, Henning AU - Weiss H AD - Max Planck Institute for Polymer Research, Ackermannweg 10,, 55128, Mainz, Germany. FAU - Schultze, Jennifer AU - Schultze J AD - Max Planck Institute for Polymer Research, Ackermannweg 10,, 55128, Mainz, Germany. FAU - Winzen, Svenja AU - Winzen S AD - Max Planck Institute for Polymer Research, Ackermannweg 10,, 55128, Mainz, Germany. FAU - Schinnerer, Meike AU - Schinnerer M AD - Institute for Physical Chemistry, Johannes Gutenberg-University Mainz, Welder Weg 11, 55099, Mainz, Germany. FAU - Koynov, Kaloian AU - Koynov K AD - Max Planck Institute for Polymer Research, Ackermannweg 10,, 55128, Mainz, Germany. FAU - Mezger, Markus AU - Mezger M AD - Max Planck Institute for Polymer Research, Ackermannweg 10,, 55128, Mainz, Germany. FAU - Haass, Nikolas K AU - Haass NK AD - The University of Queensland, The University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Brisbane, QLD, 4102, Australia. FAU - Tremel, Wolfgang AU - Tremel W AD - Institute for Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14,, 55128, Mainz, Germany. FAU - Jonuleit, Helmut AU - Jonuleit H AD - Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1,, 55131, Mainz, Germany. LA - eng PT - Journal Article DEP - 20170529 PL - Germany TA - Adv Healthc Mater JT - Advanced healthcare materials JID - 101581613 RN - 0 (Tumor Necrosis Factor-alpha) RN - 7631-86-9 (Silicon Dioxide) SB - IM MH - Cell Cycle/*drug effects MH - Cell Line, Tumor MH - Dose-Response Relationship, Drug MH - Drug Delivery Systems/*methods MH - Humans MH - *Nanoparticles/chemistry/therapeutic use MH - Neoplasms/*drug therapy/metabolism MH - Porosity MH - *Silicon Dioxide/chemistry/pharmacokinetics/pharmacology MH - *Tumor Necrosis Factor-alpha/chemistry/pharmacokinetics/pharmacology OTO - NOTNLM OT - mesoporous silica nanoparticles OT - pH-triggered release OT - proinflammatory cytokine OT - stimuli-responsive drug delivery OT - tumor necrosis factor-alpha EDAT- 2017/05/31 06:00 MHDA- 2018/03/22 06:00 CRDT- 2017/05/31 06:00 PHST- 2017/01/04 00:00 [received] PHST- 2017/03/01 00:00 [revised] PHST- 2017/05/31 06:00 [pubmed] PHST- 2018/03/22 06:00 [medline] PHST- 2017/05/31 06:00 [entrez] AID - 10.1002/adhm.201700012 [doi] PST - ppublish SO - Adv Healthc Mater. 2017 Jul;6(13). doi: 10.1002/adhm.201700012. Epub 2017 May 29.