Nanopartículas de upconversionsíntesis y aplicaciones

Laburpena

Abstract In the last decades nanochemistry has reached great interest due to the importance of developing innovative and unique materials at nanometric scale, specifically nanoparticles. The properties of nanomaterials differ from those at a larger scale, so nanochemistry open innovative ways in science to develop materials with new properties and novel performance. Upconversion nanoparticles (UCNPs) are lanthanides inorganic based nanocrystals, such as NaYF4 co-doped with lanthanides cations (such as Er3+, Yb3+, Tm3+…). UCNPs display excellent chemical, thermal and photostability, good biocompatibility, narrow bandwidth, long luminescence times, no photoblinking and no photobleaching. Most importantly, they can emit in the visible after their excitation at the near-infrared (NIR) because of their intra-configurational 4f electron transitions. Hence, UCNPs are of great interest in many fields such as security, photocatalysis or sensing and specially in biomedicine (bioimaging, photodynamic therapy…) due to the high penetration depth of the NIR light in tissues. Nanochemistry plays a crucial role in architecting UCNPs, firstly, in the development of new synthetic routes and/or control of the reaction parameters in order to achieve monodisperse and uniform UCNPs with high UC efficiency. Secondly, nanochemistry is important for surface engineering, since it deals with the convenient modification and functionalization of the UCNPs surface to provide them with desired properties and functionalities. This thesis is focused in the synthesis of new nanomaterials based on NaYF4 co-doped nanoparticles with exceptional properties and their further derivatization. Texture and phase recognition analysis (TPRA) based on electron nanodiffraction technique is used to characterize the geometry of UCNPs synthesized by the high temperature co-precipitation strategy which uses stochiometric amounts of NH4F. Here, we confirmed experimentally that despite the apparently different shapes of samples (hexagons, rods, and cubes), all the nanocrystals are actually β-phase hexagonal prisms. This is of relevance since many biological features of nanostructures, such as cellular internalization and cytotoxicity, are governed by their geometry. In addition, reproducibility in biological experiments is paramount. In addition, water-dispersible, ca. 30 nm-sized NaYF4: Er3+, Yb3+ UCNPs, capped with a polyethylene glycol (PEG) derivative and highly loaded with a singlet oxygen photosensitizer, specifically a diiodo-substituted Bodipy (IBDP), was synthesized. The photosensitizer, bearing a carboxylic group, was anchored to the UCNP surface and, at the same time, embedded in the PEG capping; the combined action of the UCNP surface and PEG facilitated the loading for an effective energy transfer and, additionally, avoided photosensitizer leaching from the nanohybrid (UCNP–IBDP@PEG). The effectiveness of the nanohybrids in generating singlet oxygen after NIR excitation with a continuous wavelength laser was evidenced by using a probe molecule. In vitro assays demonstrated that the UCNP–IBDP@PEG nanohybrid was taken up by the SH-SY5Y human neuroblastoma-derived cells showing low cytotoxicity. Moreover, ca. 50% cancer cell death was observed after NIR irradiation (45 min, 239 mW·cm-2). Steady-state and time-resolved emission studies on this nanohybrid, and on its hydrophobic analogous, shows that the Yb3+ metastable state, formed after absorption of a NIR photon, can decay via two competitive energy transfer processes: sensitization of IBDP after absorption of a second NIR photon and population of Er3+ excited states. Moreover, spontaneous adsorption of cucurbit[n]uril, CB[n] (n = 6, 7, and 8), on the surface of naked NaYF4: Er3+, Yb3+ gave rise to UCNP@CB[n] exclusion complexes. These complexes proved to be highly stable as well as highly emissive under near-infrared excitation. By using two tricyclic basic dyes (specifically, methylene blue and pyronin Y) as a proof of concept, we demonstrate that the UCNP@CB[n] (n = 6, 7) nanohybrids can form exclusion complexes with this type of dyes via the CB carbonyl free portal, i.e., UCNP@CB@dye hybrids, thus making it possible to locate a high concentration of the dyes close to the UCNP and, consequently, leading to efficient energy transfer from the UCNP to the dye. Furthermore, CB[7] was used to assemble two different nanoparticles, UCNPs and CH3NH3PbBr3 perovskite nanoparticles (PK). This innovative strategy allows to anchor the perovskite nanoparticles firmly and closely to the naked UCNPs surface, thus leading to UCn@PKCB nanohybrids. A commercial multiphoton laser scanning confocal microscope is used to demonstrate the successful assembly. This technique proves to be useful to evaluate luminescence lifetime in the range of several tens of μs and allows visualization of the extraordinarily efficient nontrivial resonance energy transfer from the upconversion nanoparticle to the perovskite after NIR excitation of the nanohybrid as well as the homogeneity of the UCn@PKCB sample. The considerable photostability of the perovskite in these nanohybrids is demonstrated by prolonged irradiation of the nanohybrid under UV light as well as under NIR light. Last but not least, UCNPs were capped with a thin polymer shell by replacing the oleate ligand of hydrophobic UCNPs by multidentate thiolate-grafting of P(MEO2MA-co-SEMA) copolymers. The presence of the 2-(2-methoxyethoxy)ethyl side chains of MEO2MA extending out of the nanohybrid made them water-dispersible and thermosensibles. The UCNP@P(MEO2MA-co-SEMA) nanohybrids exhibited an enhanced emission by up to a factor of 10, as compared with that of their hydrophobic precursor in dichloromethane and even in water (a factor of 2). Their thermoresponsiveness was modulated by the pH; this is consistent with the presence of some thiol groups at the nanohybrid periphery. Remarkably, the nanohybrid emission, as well as its stability, was almost independent of the aggregation state (in the basic-acid and temperature range studied here). The formation of stable water-dispersible UCNPs with enhanced emission, together with their amphiphilic and temperature-responsive polymer coating, is promising for building multifunctional nanostructures for intracellular imaging, therapy, and drug delivery.