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Web of knowledge for INA - MAT Contract number PCE 186 /2021 National Authority: UEFISCDI |
UNIVERSITATEA BABES BOLYAI FACULTATEA DE CHIMIE SI INGINERIE CHIMICA
Innovative strategies for safe production of advanced materials based on multifunctional ceramic and metallic nanoparticles for medical applications (INA-MAT) |
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· Obtained results:
Phase 1:
Synthesis and characterization of GNPs-ACD, GNPs-AMC and AgNPs-AMC, series of novel nanocomplexes New advanced INA-MAT nanomaterials based on multifunctionalized ceramic and metallic nanoparticles (NPs) were developed by innovative strategies for their safe production and characterized for medical applications. Two types of gold nanoparticles (GNPs) dispersions, with average size of particles under 10 nm and 10-20 nm, two kinds of silver nanoparticles (AgNPs) dispersions, average size about 13 and 40 nm, hydroxyapatite (HAP) and multi-substituted HAPs containing biologically important elements (Mg, Zn, Sr and Si), all with controlled NPs size, were synthesized. The developed manufacturing procedures were optimized. The metallic NPs were functionalized with anti-cancer drugs (ACD), obtaining innovative complexes GNP-ACD with doxorubicin, resveratrol, piperine, icariin, respectively AgNPs complexes with anti-microbial compounds (AMC), e.g. with vancomycin. All obtained INA-MAT materials were characterized by physical and chemical methods (such as XRD, TEM, SEM, EDX, AFM, FTIR, BET, DLS) and biological testing in vitro on HeLa, CaSki, MDA MB231, MCF-7 and GM-1 cancer cell cultures, respectively on bacterial cultures (e.g. Staphylococcus. aureus).
Phase 2:
Obtaining and characterization of new GNPs-ACD/HAP, GNPs-AMC/HAP or AgNPs-AMC/HAP nanomaterials and innovative GNPs-ACD/ms-HAP, GNPs-AMC/ms-HAP or AgNPs-AMC/ms-HAP nanomaterials In phase 2 of INA-MAT project, the development of new advanced nanobiomaterials based on nanoparticles (NPs) of hydroxyapatites (pure stoichiometric hydroxyapatites, HAPs, or multi-substituted hydroxyapatites, msHAPs, of various crystallinity), is crucial for their uses as essential tools in bone regeneration and as carriers for therapeutic metallic NPs (gold nanoparticles, GNPs or argint nanoparticles, AgNPs) functionalized with biomolecules, like anti-cancer drugs (ACD), antimicrobial compounds (AMC), and natural anti-oxydant compounds (NAC), assuring a synergistic effect for medical applications. In this work, gold NPs-loaded HAPs were designed, to giude the osteogenic differentiation of human mesenchimal stem cells (HMSC) through the synergistic effect of HAPs or msHAPs and GNPs, as well as various biomolecules used to functionalized GNPs. Cell viability and proliferation of HMSC were charaterized by MTT, Alamar Blue (AM) and fluoresceine diacetate (FDA) tests. The innovative antimicrobial nanomaterials using AgNPs-loaded HAPs or msHAPs functionalized with antimicrobial compounds are safety and have osteoconductive properties. A series of 40 nanobiomaterials were successfully prepared and well characterized, by several analytical techniques, XRD, FTIR, SEM, TEM. STEM, AFM, BET, as well as by biological activity. -->
Phase 3:
Obtaining and characterization of new HAP/PM/GNPs-ACD, HAP/PM/GNPs-AMC or HAP/PM/AgNPs-AMC composites and ms-HAP/PM/GNPs-ACD, ms-HAP/PM/GNPs-AMC or ms-HAP/PM/AgNPs-AMC composites, for polymers: PM: PLA, PVA or sodium alginate. Recent developments in the innovative production of nanocomposites made of ceramic nanoparticles, CM NPs: HAP and ms-HAP NPs, and metallic NPs: GNPs and/or Ag NPs, functionalized with drugs: ACD or AMC, and /or with natural components with high biological activity, such as anti-cancer, anti-microbial or anti-inflammatory, loaded by polymers, PM, have been realized in project INA-MAT, phase 3. A new approach leading to an efficient strategy of nanocomposites’ safe production was designed with enhanced nucleation and crystallization ability of AgNPs on the surface of ceramic NPs, simultaneously uncovering an increased bioactivity against various pathogens. As proof of concept, CM NPs and metallic NPs of different size and morphology were surface treated with organic molecules realizing modified layered structures able to promote composites’ formation during encapsulation into polymers’ matrix, PM. Further, the nano-biocomposites and their fine aqueous dispersions revealed remarkable bioactivity against various cancer cells and pathogens without cytotoxicity on stem cells. By considering the notable increase in bioactivity of these nano-biocomposites, which is a key parameter to allow their utilisation in medical applications, the future developments of this new approach are expected to lead to substantial improvements in the processing and performances of nano-biocomposites. A series of 42 INA-MAT nanocomposites were effectively prepared and well physical and chemical characterized, by several analytical techniques, XRD, FTIR, SEM-EDX, TEM, STEM-EDX, AFM, as well as by biological activity: agar diffusion antimicrobial tests, as well as MTT and FDA assays for cell proliferation and cytotoxicity. The results were widely disseminated by ISI and BDI articles, communications at national and international scientific conferences and Ph.D. theses. |