Spring, BQ;
Bryan Sears, R;
Zheng, LZ;
Mai, Z;
Watanabe, R;
Sherwood, ME;
Schoenfeld, DA;
... Hasan, T; + view all
(2016)
A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways.
Nature Nanotechnology
, 11
(4)
10.1038/nnano.2015.311.
Preview |
Text
NNANO.2015.311_auproof.pdf - Accepted Version Download (3MB) | Preview |
Abstract
Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)-a multikinase inhibitor-encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities.
| Type: | Article |
|---|---|
| Title: | A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/nnano.2015.311 |
| Publisher version: | http://dx.doi.org/10.1038/nnano.2015.311 |
| Language: | English |
| Keywords: | Biomedical engineering, Drug delivery, Nanoparticles, Nanotechnology in cancer Photocatalysis |
| 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 Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1477301 |
Archive Staff Only
 |
View Item |
