Nanometric particles of titania, brookite and rutile polymorphs were synthesised by thermolysis of TiCl 4 in concentrated HCl solutions. The Cl : Ti molar ratio seems to be the key factor in determining the crystalline phases and their relative proportions as well as the particle size and a large proportion of brookite can be obtained under specific conditions. The complex Ti(OH) 2 (Cl) 2 (OH 2 ) 2 seems to be the precursor of the brookite phase. The presence of chloride ions is also necessary to stabilise brookite in suspension. Depending on the acidity and the ageing conditions, different morphologies of brookite nanoparticles are obtained, namely spheroidal particles or platelets. Stable sols of pure brookite are obtained by peptization of the solid phase.
These findings, supported by good tolerance, provide the basis for developing this new type of nanoparticle as a promising anticancer approach in human patients.
The situation of the COVID-19 pandemic reminds us that we permanently need high-value flexible solutions to urgent clinical needs including simplified diagnostic technologies suitable for use in the field and for delivering targeted therapeutics. From our perspective nanotechnology is revealed as a vital resource for this, as a generic platform of technical solutions to tackle complex medical challenges. It is towards this perspective and focusing on nanomedicine that we take issue with Prof Park's recent editorial published in the Journal of Controlled Release. Prof. Park argued that in the last 15 years nanomedicine failed to deliver the promised innovative clinical solutions to the patients (Park, K. The beginning of the end of the nanomedicine hype. Journal of Controlled Release, 2019; 305, 221–222 [1]. We, the ETPN (European Technology Platform on Nanomedicine) [ 2 ], respectfully disagree. In fact, the more than 50 formulations currently in the market, and the recent approval of 3 key nanomedicine products (e. g. Onpattro, Hensify and Vyxeos), have demonstrated that the nanomedicine field is concretely able to design products that overcome critical barriers in conventional medicine in a unique manner, but also to deliver within the cells new drug-free therapeutic effects by using pure physical modes of action, and therefore make a difference in patients lives. Furthermore, the >400 nanomedicine formulations currently in clinical trials are expecting to bring novel clinical solutions (e.g. platforms for nucleic acid delivery), alone or in combination with other key enabling technologies to the market, including biotechnologies, microfluidics, advanced materials, biomaterials, smart systems, photonics, robotics, textiles, Big Data and ICT (information & communication technologies) more generally. However, we agree with Prof. Park that “ it is time to examine the sources of difficulty in clinical translation of nanomedicine and move forward “. But for reaching this goal, the investments to support clinical translation of promising nanomedicine formulations should increase, not decrease. As recently encouraged by EMA in its roadmap to 2025, we should create more unity through a common knowledge hub linking academia, industry, healthcare providers and hopefully policy makers to reduce the current fragmentation of the standardization and regulatory body landscape. We should also promote a strategy of cross-technology innovation, support nanomedicine development as a high value and low-cost solution to answer unmet medical needs and help the most promising innovative projects of the field to get better and faster to the clinic. This global vision is the one that the ETPN chose to encourage for the last fifteen years. All actions should be taken with a clear clinical view in mind, “ without any fanfare ”, to focus “ on what matters in real life ”, which is the patient and his/her quality of life....
Nanoparticles of anatase with mean size in the range 5-10 nm were prepared by precipitation of TiCl 4 in aqueous medium in the range 2 ¡ pH ¡ 6. Hydroxylation of TiCl 4 at room temperature leads instantaneously to an amorphous titanium oxyhydroxide phase which crystallizes as anatase upon aging at 60 uC in suspension. Small amounts of brookite or rutile are concurrently obtained depending on the acidity. The size of anatase particles was characterized by X-ray diffraction, electron microscopy and Raman spectroscopy. The latter was also used to determine the particle size and to characterize the crystallinity of particles through the phonon confinement effect. The particle size, dependent on the acidity, is closely related to the electrostatic surface charge density of particles. The size variation was interpreted as resulting from a lowering of the interfacial tension due to the protonation of particle surface groups. Composite materials were synthesized by polymerisation of silica in aqueous sols of anatase. The dispersed anatase nanoparticles are stable against the transformation to rutile up to 1000 uC.
BackgroundHafnium oxide, NBTXR3 nanoparticles were designed for high dose energy deposition within cancer cells when exposed to ionizing radiation. The purpose of this study was to assess the possibility of predicting in vitro the biological effect of NBTXR3 nanoparticles when exposed to ionizing radiation.MethodsCellular uptake of NBTXR3 nanoparticles was assessed in a panel of human cancer cell lines (radioresistant and radiosensitive) by transmission electron microscopy. The radioenhancement of NBTXR3 nanoparticles was measured by the clonogenic survival assay.ResultsNBTXR3 nanoparticles were taken up by cells in a concentration dependent manner, forming clusters in the cytoplasm. Differential nanoparticle uptake was observed between epithelial and mesenchymal or glioblastoma cell lines. The dose enhancement factor increased with increase NBTXR3 nanoparticle concentration and radiation dose. Beyond a minimum number of clusters per cell, the radioenhancement of NBTXR3 nanoparticles could be estimated from the radiation dose delivered and the radiosensitivity of the cancer cell lines.ConclusionsOur preliminary results suggest a predictable in vitro biological effect of NBTXR3 nanoparticles exposed to ionizing radiation.
The coordination−insertion ring-opening polymerization of ε-caprolactone was initiated from amine or hydroxyl groups spread over the surface of silica (ca. 30 nm) or cadmium sulfide (ca. 1.5 nm) nanoparticles, respectively. The initiation selectively occurred from the surface functional groups after activation into aluminum alkoxides species. The covalent grafting of the polyester chains was confirmed by the solubilization of the nanoparticles in organic solvents, e.g., CHCl3 and THF for silica nanoparticles and toluene for CdS nanoparticles, at least when the surface-grafted PCL chains were long enough. In the case of silica nanoparticles, the linear dependence of the PCL molar mass as determined by 1H NMR analysis on the initial monomer-to-amine ratio confirmed the controlled character of the polymerization. Transmission electron microscopy of thin films of PCL-grafted CdS revealed an homogeneous dispersion of the semiconducting nanoparticles throughout the polyester matrix.
Radiotherapy has a universal and predictable mode of action, that is, a physical mode of action consisting of the deposit of a dose of energy in tissues. Tumour cell damage is proportional to the energy dose. However, the main limitation of radiotherapy is the lack of spatial control of the deposition of energy, that is, it penetrates the healthy tissues, damages them and renders unfeasible delivery of an efficient energy dose when tumours are close to important anatomical structures. True nanosized radiation enhancers may represent a disruptive approach to broaden the therapeutic window of radiation therapy. They offer the possibility of entering tumour cells and depositing high amounts of energy in the tumour only when exposed to ionizing radiations (on/off activity). They may unlock the potential of radiation therapy by rendering the introduction of a greater energy dose, exactly within the tumour structure without passing through surrounding tissues feasible. Several nanosized radiation enhancers have been studied in in vitro and in vivo models with positive results. One agent has received the authorization to conduct clinical trials for human use. Opportunities to improve outcomes for patients receiving radiotherapy, to create new standards of care and to offer solutions to new patient populations are looked over here.
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