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Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model

López-Dávila, V; Magdeldin, T; Welch, H; Dwek, MV; Uchegbu, I; Loizidou, M; (2016) Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model. Nanomedicine , 11 (4) pp. 331-344. 10.2217/nnm.15.206. Green open access

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Abstract

AIM: In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model. MATERIALS & METHODS: We used 3beta-(N-[N',N'-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids). RESULTS: Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids. CONCLUSION: These results support the role of nanoparticles in improving drug delivery and highlight the need to include 3D cancer models in early phases of drug development.

Type: Article
Title: Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model
Open access status: An open access version is available from UCL Discovery
DOI: 10.2217/nnm.15.206
Publisher version: http://dx.doi.org/10.2217/nnm.15.206
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 License To view a copy of this licence, see: http://creativecommons.org/licenses/by/4.0/
Keywords: 3D culture, AZD6244, artificial cancer mass, chemotherapy, colorectal cancer, drug delivery, liposomes, micelles, tumoroids
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/1474308
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