title: Multifunctional gold-nanoparticles: A nanovectorization tool for the targeted delivery of novel chemotherapeutic agents.
abstract: Due to their small size and unique properties, multifunctional nanoparticles arise as versatile delivery systems easily grafted with a vast array of functional moieties, such as anticancer cytotoxic chemotherapeutics and targeting agents. Here, we formulated a multifunctional gold-nanoparticle (AuNP) system composed of a monoclonal antibody against epidermal growth factor receptor (EGFR) (anti-EGFR D-11) for active targeting and a Co(II) coordination compound [CoCl(H2O)(phendione)2][BF4] (phendione=1,10-phenanthroline-5,6-dione) (TS265) with proven antiproliferative activity towards cancer cells (designated as TargetNanoTS265). The efficacy of this nanoformulation, and the non-targeted counterpart (NanoTS265), were evaluated in vitro using cancer cell models and in vivo using mice xenografts. Compared to the free compound, both nanoformulations (TargetNanoTS265 and NanoTS265) efficiently delivered the cytotoxic cargo in a controlled selective manner due to the active targeting, boosting tumor cytotoxicity. Treatment of HCT116-derived xenografts tumors with TargetNanoTS265 led to 93% tumor reduction. This simple conceptual nanoformulation demonstrates the potential of nanovectorization of chemotherapeutics via simple assembly onto AuNPs of BSA/HAS-drug conjugates that may easily be expanded to suit other cargo of novel compounds that require optimized controlled delivery to cancer target.
authors.affiliation: UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Campus de Caparica, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; CQE, Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: ma.fernandes@fct.unl.pt.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Fernandes
authors.affiliation: UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Campus de Caparica, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Jesus
authors.affiliation: UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Campus de Caparica, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Martins
authors.affiliation: UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Campus de Caparica, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Figueiredo
authors.affiliation: UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Campus de Caparica, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rosa
authors.affiliation: CQE, Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal; Área Departamental de Engenharia Química, Instituto Superior de Engenharia de Lisboa, R. Conselheiro Emídio Navarro, 1959-007 Lisboa, Portugal.
authors.forename: Luísa M R D R S
authors.initials: LM
authors.lastname: Martins
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Maria Luísa
authors.initials: ML
authors.lastname: Corvo
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Manuela C
authors.initials: MC
authors.lastname: Carvalheiro
authors.affiliation: MARE - Marine and Environmental Sciences Centre, Departamento de Ciências e Engenharia do Ambiente, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Costa
authors.affiliation: UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Campus de Caparica, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. Electronic address: pmvb@fct.unl.pt.
authors.forename: Pedro V
authors.initials: PV
authors.lastname: Baptista
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D056831:Coordination Complexes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005347:Fibroblasts; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004337:Drug Carriers; D058726:Nanoconjugates; D012709:Serum Albumin; D003035:Cobalt; D011092:Polyethylene Glycols; D006046:Gold; D066246:ErbB Receptors; D017239:Paclitaxel
keywords: Cancer therapy; Colorectal cancer; Gold nanoparticles; Lung cancer; Metal complexes; Nanomedicine; Targeting