Journal
JOURNAL OF CONTROLLED RELEASE
Volume 230, Issue -, Pages 57-63Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.03.040
Keywords
Theranosis; Liposomes; Sonoporation; MRI; US-triggered drug release; Cancer
Funding
- University of Torino/Compagnia San Paolo (project Innovative Nanosized Theranostic Agents) [ORTO114HLF]
- EU-COST Action TD1004 (Theragnostics Imaging and Therapy)
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The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent ( Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T-1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent ( Doxorubicin, liposomes, Gadoteridol) are approved for human use. (C) 2016 Elsevier B.V. All rights reserved.
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