title: Enhanced Antimetastatic Activity of the Ruthenium Anticancer Drug RAPTA-C Delivered in Fructose-Coated Micelles.
abstract: The ruthenium complex-dichlororuthenium (II) (p-cymene) (1,3,5-triaza-7-phosphaadamantane) (RAPTA-C)-has shown to be remarkably effective at suppressing the growth of solid tumor metastases. However, poor delivery efficacy and the lack of targeting ability of the common drug delivery system pose significant obstacles to maximize the therapeutic benefit of RAPTA-C. Inspired by the overexpression of GLUT5 transporter on the surface of breast cancer tissues but not the healthy mammary tissues, the use of d-fructose as the targeting moiety of the drug carrier can significantly improve the cellular uptake of nanoparticles, thus further enhancing the therapeutic efficiency of RAPTA-C. In this work, fructose-micelles and 2-hydroxyethyl acrylate (HEA)-micelles are prepared to investigate the difference in cellular uptake. It is found that glycopolymer leads to an increased uptake by breast cancer cells, while the HEA-micelles show less uptake. This behavior is also reflected by the slightly faster movement of fructose-coated micelles in MCF-7 tumor spheroid models using light sheet microscopy as analytical tool. The incorporation of RAPTA-C into micelles can enhance the inhibitory effect of the ruthenium drug demonstrated using invasion, chemotaxis, and haptotaxis assays. As a result, fructose-coated nanoparticles can be a promising drug delivery platform of RAPTA-C for the treatment of metastatic breast cancer.
authors.affiliation: Centre for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Lu
authors.affiliation: Centre for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Centre for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Janina-Miriam
authors.initials: JM
authors.lastname: Noy
authors.affiliation: Centre for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Lu
authors.affiliation: Centre for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Martina H
authors.initials: MH
authors.lastname: Stenzel
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000081007:Cymenes; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D005260:Female; D005632:Fructose / Q000737:chemistry*; D015870:Gene Expression; D051296:Glucose Transporter Type 5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000179:Acrylates; D000970:Antineoplastic Agents; D000081007:Cymenes; D004337:Drug Carriers; D051296:Glucose Transporter Type 5; D008823:Micelles; D009363:Neoplasm Proteins; D009942:Organometallic Compounds; C495726:SLC2A5 protein, human; C530402:dichloro(4-cymene)(1,3,5-triaza-7-phosphatricyclo(3.3.1.1)decane)ruthenium(II); C035957:2-hydroxyethyl acrylate; D005632:Fructose
keywords: micelles; multicellular tumor spheroids; ruthenium drugs; tumor metastasis