title: MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.
abstract: Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Nguyen Quoc
authors.initials: NQ
authors.lastname: Vinh
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Naka
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cabral
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murayama
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kaida
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Nursing, Shiga University of Medical Science, Shiga, Japan;
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Biomedical Innovation Center, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000401:mortality; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000401:mortality; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008823:Micelles; D010984:Platinum / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D010984:Platinum
keywords: Gd-DTPA/DACHPt-loaded micelles; drug delivery; hepatocellular carcinoma; polymeric micelles