title: The release of Doxorubicin from liposomes monitored by MRI and triggered by a combination of US stimuli led to a complete tumor regression in a breast cancer mouse model.
abstract: 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-T1 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.
authors.affiliation: Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rizzitelli
authors.affiliation: Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Giustetto
authors.affiliation: Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Faletto
authors.affiliation: Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Delli Castelli
authors.affiliation: Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Aime
authors.affiliation: Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy. Electronic address: enzo.terreno@unito.it.
authors.forename: E
authors.initials: E
authors.lastname: Terreno
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D000069453:Ultrasonic Waves
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C506643:liposomal doxorubicin; C062402:gadoteridol; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005682:Gadolinium
keywords: Cancer; Liposomes; MRI; Sonoporation; Theranosis; US-triggered drug release