Spring, BQ; Bryan Sears, R; Zheng, LZ; Mai, Z; Watanabe, R; Sherwood, ME; Schoenfeld, DA; ... Hasan, T; + view all Spring, BQ; Bryan Sears, R; Zheng, LZ; Mai, Z; Watanabe, R; Sherwood, ME; Schoenfeld, DA; Pogue, BW; Pereira, SP; Villa, E; Hasan, T; - view fewer (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.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item