Project NORTH aims at combining lanthanide doped inorganic materials with organosilica materials to form hybrid nanomaterials simultaneously working as luminescence nanothermometers and drug delivery vehicles or delivery vehicles for photodynamic therapy agents.
The project proposal focused efforts on the LiLuF4 host inorganic material, however due earlier observed ion migration issues in this host material, some of the work was shifted to other inorganic host matrixes (NaYF4, LaF3, NaGdF4 and Na3ZrF7), while at the same time further exploring and learning to hinder emissive ion migration in the LiLuF4 host to be able to employ it in further parts of the project. In project NORTH we have carried out a detailed investigation of the ion migration process in LiLuF4:Er,Yb@LiLuF4 core-shell nanoparticles and looked into find solutions to stop this process based on synthesis modifications as well as building a heterogenous shell forming LiLuF4:Er,Yb@LiYF4 core-shell structures (STEM, EDX maps, XRF, and high temperature thermometry were employed for this investigation). We have also investigated how different synthesis routes affect this ion migration process. The gained knowledge is further allowing us to successfully build heterogenous LiLuF4:Ln@LiYF4 core-shell structures containing various thermometry systems, with significantly hindered ion migration, as well as hybrid LiLuF4:Ln-PMO materials.
In a first attempt to combine thermometry and drug delivery in one system HPMO@NaYF4:Er,Yb and HPMO@NaYF4:Er,Yb,Tm nanorattles (where HPMO = hollow PMO), working both as a thermometer and Doxorubicin (DOX) drug delivery capsule were prepared and reported. The hollow PMOs are first filled with inorganic precursors which upon heat treatment convert to nanoparticles building into the HPMO void, yielding nanorattle type structures. Such materials show very good Yb-Er and Yb-Er-Tm upconversion (UC) thermometry in the physiological range (20-50 C). We have also shown that the nanorattle type structures can be used for pH dependent DOX drug delivery without compromising the thermometry properties. We have compared the release of several types of PMO materials and the final nanorattle type structures, and although the PMOs show very good loading, the release time is much faster from the nanorattle materials. Cytotoxicity of human dermal cells was carried out for these materials to show their lack of toxicity to the human body and potential for application in the biomedical field.
To compare our hybrid PMO-inorganic thermometry-drug release vehicles we have also added to the project an investigation of several purely inorganic vehicles, which we prove also show simultaneous thermometry and drug delivery. For this purpose Y2O3 and Y2O2SO4 hollow spheres doped with Yb-Er ions were developed. In a separate study YOF hollow spheres doped with Yb-Er-Gd ions were also prepared. These materials were tested for their UC Boltzmann thermometry, pH-dependant DOX drug delivery and cytotoxicity to human dermal cells. The results show that the purely inorganic vehicles can work as simultaneous thermometers and drug delivery vehicles without compromising their performance. However, the DOX release is slightly better when working with hybrid materials. Also, hybrid materials of the PMO-inorganic type show more promise for further functionalizations and modifications for example for targeting specific cancer cells.
