title: A Micro/Nano Composite for Combination Treatment of Melanoma Lung Metastasis.
abstract: The successful treatment of malignant disease generally requires the use of multiple therapeutic agents that are coordinated in a spatiotemporal manner to enable synergy. Here, a porous silicon-based micro/nano composite (MNC) that is capable of simultaneously delivering chemotherapeutic agents and small interfering RNA (siRNA) to the lungs following intravenous injection is designed. The pores of the silicon microparticles are loaded with B-Raf proto-oncogene serine/threonine kinase (BRAF) siRNA-containing liposomes, while the surface is conjugated with docetaxel-encapsulated polymeric nanoparticles. The synergistic antitumor effect of the MNC is demonstrated in vitro in melanoma cells and in vivo using a mouse model for melanoma lung metastasis. The MNC displays superior therapeutic efficacy and increased accumulation in metastatic melanoma lesions in the lungs in comparison to combination therapy with liposomes and polymers. The results indicate that the MNC can be used as an effective delivery vehicle for simultaneous enrichment of multiple therapeutic agents in the lungs.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Mu
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Wolfram
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Zaian
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Tony Ye
authors.initials: TY
authors.lastname: Hu
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Elvin
authors.initials: E
authors.lastname: Blanco
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.|Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.|Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy*; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy*; D008819:Mice, Nude; D055616:Microtechnology; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D048493:Proto-Oncogene Proteins B-raf
keywords: biomaterials; drug delivery; melanoma lung metastasis; polymeric materials; siRNA delivery; silicon microdisks