RESUMEN
Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound [Zn(DION)2]Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR). Selective delivery of the ZnD nanosystem to cancer cells was achieved by active targeting via cetuximab, NanoZnD, which significantly inhibited cell proliferation and triggered the death of resistant tumor cells, thus improving efficacy. In vivo studies in a colorectal DOX-resistant model corroborated the capability of NanoZnD for the selective targeting of cancer cells, leading to a reduction of tumor growth without systemic toxicity. This approach highlights the potential of gold nanoformulations for the targeting of drug-resistant cancer cells.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Oro/química , Nanopartículas del Metal/química , Zinc/administración & dosificación , Animales , Antineoplásicos/farmacología , Cetuximab/administración & dosificación , Cetuximab/farmacología , Complejos de Coordinación/administración & dosificación , Complejos de Coordinación/farmacología , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Células HCT116 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Zinc/farmacologíaRESUMEN
BACKGROUND: Despite continuous efforts, the treatment of canine cancer has still to deliver effective strategies. For example, traditional chemotherapy with doxorubicin and/or docetaxel does not significantly increase survival in dogs with canine mammary tumors (CMTs). AIMS: Evaluate the efficiency of two metal compounds [Zn(DION)2 ]Cl (TS262, DION = 1,10-phenanthroline-5,6-dione) and [CoCl(H2 O)(DION)2 ][BF4 ] (TS265) and novel nanovectorizations designed to improve the anti-cancer efficacy of these compounds in a new CMT derived cell line (FR37-CMT). MATERIALS AND METHODS: FR37-CMT cells were exposed to different concentrations of TS262 and TS265 and two new nanoparticle systems and cellular viability was determined. These nanosystems are composed of polyethylene-glycol, bovine-serum-albumin and TS262 or TS265 (NanoTS262 or NanoTS265, respectively). RESULTS: In FR37-CMT, TS262 and TS265 displayed IC50 values well below those displayed by doxorubicin and cisplatin. The nanovectorizations further decreased the IC50 values. DISCUSSION: TS262 and TS265 proved to be effective against FR37-CMT cells and more effective than of doxorubicin and cisplatin. The Nanosystems efficiently delivered the cytotoxic cargo inducing a significant reduction of cell viability in FR37-CMT cell line when compared to the free compounds. CONCLUSIONS: TS262 and TS265 are compounds with potential in the treatment of CMTs. NanoTS262 and NanoTS265 demonstrate that such simple nanovectorization via gold nanoparticles shows tremendous potential as anti-cancer formulations, which may easily be expanded to suit other cargo.
Asunto(s)
Antineoplásicos/uso terapéutico , Cobalto/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Oro/uso terapéutico , Neoplasias Mamarias Animales/tratamiento farmacológico , Nanopartículas del Metal/uso terapéutico , Compuestos de Zinc/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Cobalto/administración & dosificación , Perros , FemeninoRESUMEN
The highly efficient eco-friendly synthesis of ketones (yields over 99%) from secondary alcohols is achieved by combination of [FeCl2{η(3)-HC(pz)3}] (pz = pyrazol-1-yl) supported on functionalized multi-walled carbon nanotubes and microwave irradiation, in a solvent-free medium. The carbon homoscorpionate iron(ii) complex is the first one of this class to be used as catalyst for the oxidation of alcohols.