title: A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways.
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.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.|Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Bryan Q
authors.initials: BQ
authors.lastname: Spring
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.|Department of Chemistry, Emmanuel College, Boston, Massachusetts 02115, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bryan Sears
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Lei Zak
authors.initials: LZ
authors.lastname: Zheng
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Mai
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Reika
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Sherwood
authors.affiliation: Massachusetts General Hospital and Harvard University, Biostatistics Unit, Boston, Massachusetts 02114, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.affiliation: UCL Institute for Liver and Digestive Health, University College London, Royal Free Hospital Campus, London NW3 2QG, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Pereira
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Villa
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.|Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000813:Anilides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D011725:Pyridines; C504224:benzoporphyrin D; C558660:cabozantinib