Desmaële, D. (Didier)
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- Decoration of squalenoyl-gemcitabine nanoparticles with squalenyl-hydroxybisphosphonate for the treatment of bone tumors(Wiley, 2021-12-14) Sebastian, V. (Víctor); Blanco-Prieto, M.J. (María José); Desmaële, D. (Didier); Couvreur, P. (Patrick); Rodriguez-Nogales, C. (Carlos)Therapeutic perspectives of bone tumors such as osteosarcom are main restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancers qualene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was synthetized by chemical conjugation of a 1-hydroxyl-1,1-bi-sphosphonatemoiety to the squalenechain. This amphiphilic compound was inserted onto squalenoyl-gemcitabinenano-particles using the nanoprecipitation method. The co-assemblyled to nanoconstructsof 75 nm, with different morphology and colloidal properties. The presence of squalenyl-hydroxybi-sphosphonate 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 pedia tricoste osarcomacells. Furtherin vivo studies will shed lighton the potential of these nano medicines for the treatment of bones arcomas.
- Combinatorial Nanomedicine Made of Squalenoyl-Gemcitabine and Edelfosine for the Treatment of Osteosarcoma(2020) Blanco-Prieto, M.J. (María José); Desmaële, D. (Didier); Moreno, H. (Haritz); Couvreur, P. (Patrick); Lecanda, F. (Fernando); Rodriguez-Nogales, C. (Carlos); Zandueta, C. (Carolina)Due to chemoresistance and a high propensity to formlungmetastasis, survival ratesin 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