RESUMO
A new platform constituted by engineered responsive nanoparticles transported by human mesenchymal stem cells is here presented as a proof of concept. Ultrasound-responsive mesoporous silica nanoparticles are coated with polyethylenimine to favor their effective uptake by decidua-derived mesenchymal stem cells. The responsive-release ability of the designed nanoparticles is confirmed, both in vial and in vivo. In addition, this capability is maintained inside the cells used as carriers. The migration capacity of the nanoparticle-cell platform towards mammary tumors is assessed in vitro. The efficacy of this platform for anticancer therapy is shown against mammary tumor cells by inducing the release of doxorubicin only when the cell vehicles are exposed to ultrasound.
Assuntos
Decídua/citologia , Portadores de Fármacos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas , Animais , Células Cultivadas , Doxorrubicina/administração & dosagem , Feminino , Humanos , Camundongos , Porosidade , Ratos Sprague-Dawley , Dióxido de Silício , Ondas UltrassônicasRESUMO
Silicon-substituted hydroxyapatites have been deposited onto Ti6Al4V substrates by sol-gel technology. The Ca(10)(PO(4))(6-x-y)(SiO(4))(x)(CO(3))(y)(OH)(2-x+y) coatings obtained, with silicon contents up to x=1 (2.8 wt.%), show a homogeneous and crack-free surface composed of particles smaller than 20 nm. The silicon enters into the apatite structure in the form of SiO(4)(4-) groups that partially substitute the PO(4)(3-) groups. The Si content and the Ca/P molar ratio of the coatings agree with those originally introduced in the sols. Layers with thicknesses around 600 nm show adhesion strengths superior to 20 MPa as determined by a pull-out test. The formation of an apatite layer onto these coatings after immersion in a simulated body fluid is enhanced by the presence of silicon.
Assuntos
Materiais Revestidos Biocompatíveis/química , Hidroxiapatitas/química , Silício/química , Adesividade , Ligas , Géis , Técnicas In Vitro , Teste de Materiais , Microscopia Eletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio/química , Difração de Raios XRESUMO
The method described in this work, termed GELPOR3D, is characterised by its simplicity of use, low-cost equipment, compositional flexibility, and lack of aggressive or toxic solvents or other thermal treatment. This technique ensures the generation of a three-dimensional network of interconnected pores (300-900 microm); in addition, a random and not necessarily connected porosity is generated, yielding a hierarchical porous architecture from the macro to the molecular scale. The interconnected pores, large enough to ensure an adequate vascularization and new tissue ingrowth, can be obtained by pouring a slurry containing a biodegradable thermogel (such as agarose and gellan) and a ceramic into a mold consisting of a three-dimensional network of rigid filaments. Additional pore distributions in the macropore region can be tailored as a function of the drying/preservation technology (10-100 microm) or the interaction between the inorganic particles coated by the polymeric components (0.1-1 microm). Moreover, porosity in the mesopore range can be created by shaping ceramics such as mesoporous silica or nanocrystalline carbonatehydroxyapatite. In addition to the various bioceramics that have been successfully shaped, this method is flexible enough to allow the introduction of certain substances whose controlled release may help to avoid some negative effects that usually appear with the implantation of a material, i.e. infection, inflammation, etc., or to simplify some of the many steps required for the successful integration of a graft.