Revistas
Revista:
CHEMMEDCHEM
ISSN:
1860-7179
Año:
2021
Vol.:
16
N°:
24
Págs.:
3730 - 3738
Therapeutic perspectives of bone tumors such as osteosarcoma remain restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancer squalene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was synthetized by chemical conjugation of a 1-hydroxyl-1,1-bisphosphonate moiety to the squalene chain. This amphiphilic compound was inserted onto squalenoyl-gemcitabine nanoparticles using the nanoprecipitation method. The co-assembly led to nanoconstructs of 75 nm, with different morphology and colloidal properties. The presence of squalenyl-hydroxybisphosphonate enhanced the nanoparticles binding affinity for hydroxyapatite, a mineral present in the bone. Moreover, the in vitro anticancer activity was preserved when tested in commercial and patient-treated derived pediatric osteosarcoma cells. Further in vivo studies will shed light on the potential of these nanomedicines for the treatment of bone sarcomas.
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN:
0378-5173
Año:
2021
Vol.:
608
Págs.:
121058
Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as alpha v integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to specifically target tumor cells within these altered matrices by employing nanomedicine and combination therapy. Loading the conventional cytotoxic drug etoposide into nanoparticles significantly increased its efficacy in neuroblastoma cells. We noted high synergy between etoposide and cilengitide, a highaffinity cyclic pentapeptide alpha v integrin antagonist. The results of this study highlight the need to characterize cell-extracellular matrix interactions, to improve patient care in high-risk neuroblastoma.
Revista:
CANCERS
ISSN:
2072-6694
Año:
2020
Vol.:
12
N°:
7
Págs.:
1895
Due to chemoresistance and a high propensity to form lung metastasis, survival rates in pediatric osteosarcoma (OS) are poor. With the aim to improve anticancer activity in pediatric OS, a multidrug nanomedicine was designed using the alkyl-lysophospholipid edelfosine (EF) co-assembled with squalenoyl-gemcitabine (SQ-Gem) to form nanoassemblies (NAs) of 50 nm. SQ-Gem/EF NAs modified the total Gem pool exposure in the blood stream in comparison with SQ-Gem NAs, which correlated with a better tolerability and a lower toxicity profile after multiple intravenous administrations in mice. For in vivo preclinical assessment in an orthotopic OS tumor model, P1.15 OS cells were intratibially injected in athymic nude mice. SQ-Gem/EF NAs considerably decreased the primary tumor growth kinetics and reduced the number of lung metastases. Our findings support the candidature of this anticancer nanomedicine as a potential pediatric OS therapy.
Autores:
Rodríguez, Carlos; Mura, S.; Couvreur, P. (Autor de correspondencia); et al.
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN:
0378-5173
Despite the great advances accomplished in the treatment of pediatric cancers, recurrences and metastases still exacerbate prognosis in some aggressive solid tumors such as neuroblastoma and osteosarcoma. In view of the poor efficacy and toxicity of current chemotherapeutic treatments, we propose a single multitherapeutic nanotechnology-based strategy by co-assembling in the same nanodevice two amphiphilic antitumor agents: squalenoyl-gemcitabine and edelfosine. Homogeneous batches of nanoassemblies were easily formulated by the nanoprecipitation method. Their anticancer activity was tested in pediatric cancer cell lines and pharmacokinetic studies were performed in mice. In vitro assays revealed a synergistic effect when gemcitabine was co-administered with edelfosine. Squalenoyl-gemcitabine/edelfosine nanoassemblies were found to be capable of intracellular translocation in patient-derived metastatic pediatric osteosarcoma cells and showed a better antitumor profile than squalenoyl-gemcitabine nanoassemblies alone. The intravenous administration of this combinatorial nanomedicine in mice exhibited a controlled release behavior of gemcitabine and diminished edelfosine plasma peak concentrations. These findings make it a suitable pre-clinical candidate for childhood cancer therapy.
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
ISSN:
0939-6411
Año:
2019
Vol.:
144
Págs.:
165 - 173
Among anticancer nanomedicines, squalenoyl nanocomposites have obtained encouraging outcomes in a great variety of tumors. The prodrug squalenoyl-gemcitabine has been chosen in this study to construct a novel multidrug nanosystem in combination with edelfosine, an alkyl-lysophopholipid with proven anticancer activity. Given their amphiphilic nature, it was hypothesized that both anticancer compounds, with complementary molecular targets, could lead to the formation of a new multitherapy nanomedicine. Nanoassemblies were formulated by the nanoprecipitation method and characterized by dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy. Because free edelfosine is highly hemolytic, hemolysis experiments were performed using human blood erythrocytes and nanoassemblies efficacy was evaluated in a patient-derived metastatic pediatric osteosarcoma cell line. It was observed that these molecules spontaneously self-assembled as stable and monodisperse nanoassemblies of 51 +/- 1 nm in a surfactant/polymer free-aqueous suspension. Compared to squalenoyl-gemcitabine nanoassemblies, the combination of squalenoyl-gemcitabine with edelfosine resulted in smaller pArtículo size and a new supramolecular conformation, with higher stability and drug content, and ameliorated antitumor profile.
Nacionales y Regionales
Título:
Regeneración cerebral mediante células madre y factore neurotróficos incluidos en biomaterailes tridimensionales: apliacación en la enfermedad de parkinson.
Código de expediente:
66-2019
Investigador principal:
María José Blanco Prieto
Financiador:
GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
Convocatoria:
2019 GN Proyectos de Investigación en salud
Fecha de inicio:
19/11/2019
Fecha fin:
18/11/2023
Importe concedido:
80.000,00€
Otros fondos:
Fondos FEDER
Título:
Nueva generación de plataformas teragnósticas contra el cáncer asistidas por partículas superparamagnéticas
Código de expediente:
0011-1383-2019-000005 PC072
Investigador principal:
María José Blanco Prieto
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2019 GN Centros
Fecha de inicio:
01/12/2018
Fecha fin:
30/11/2019
Importe concedido:
113.465,43€
Otros fondos:
-
Título:
Nanovectores para administración directa, loco-regional e intravenosa controlada de fármacos antitumorales. Estrategias para minimizar los efectos adversos y
maximizar la respuesta terapéutica. ONCOLIBERYX
Código de expediente:
CPP2021-008362
Investigador principal:
María José Blanco Prieto
Financiador:
AGENCIA ESTATAL DE INVESTIGACION
Convocatoria:
2021 AEI Proyectos en Colaboración Público Privada
Fecha de inicio:
01/03/2022
Fecha fin:
28/02/2025
Importe concedido:
423.957,00€
Otros fondos:
Fondos MRR
Otros (PIUNA, fundaciones, contratos…)
Título:
Optimización de la quimioterapia en sarcomas óseos pediátricos mediante el uso de nanopartículas lipídicas
Código de expediente:
CI14142069BLAN
Investigador principal:
María José Blanco Prieto
Financiador:
ASOCIACION ESPAÑOLA CONTRA EL CANCER
Convocatoria:
2014 AECC Cancer Infantil
Fecha de inicio:
01/10/2014
Fecha fin:
30/09/2019
Importe concedido:
150.000,00€