Glioblastoma
multiforme is the most aggressive brain tumor, due
to its high invasiveness and genetic heterogeneity. Moreover, the
blood–brain barrier prevents many drugs from reaching a therapeutic
concentration at the tumor site, and most of the chemotherapeutics
lack in specificity toward cancer cells, accumulating in both healthy
and diseased tissues, with severe side effects. Here, we present in
vitro investigations on lipid-based nanovectors encapsulating a drug,
nutlin-3a, and superparamagnetic iron oxide nanoparticles, to combine
the proapoptotic action of the drug and the hyperthermia mediated
by superparamagnetic iron oxide nanoparticles stimulated with an alternating
magnetic field. The nanovectors are functionalized with the peptide
angiopep-2 to induce receptor-mediated transcytosis through the blood–brain
barrier and to target a receptor overexpressed by glioma cells. The
glioblastoma multiforme targeting efficiency and the blood–brain
barrier crossing abilities were tested through in vitro fluidic models,
where different human cell lines were placed to mimic the tumor microenvironment.
These nanovectors successfully cross the blood–brain barrier
model, maintaining their targeting abilities for glioblastoma multiforme
with minimal interaction with healthy cells. Moreover, we showed that
nanovector-assisted hyperthermia induces a lysosomal membrane permeabilization
that not only initiates a caspase-dependent apoptotic pathway, but
also enhances the anticancer efficacy of the drug.
In the typical colloidal synthesis as described by Protesescu et al.
2CsPbBr 3 NCs are stabilized with long chain organic ligands (oleylamine -OlAm -and oleic acid -OlAc -dissolved in octadecene -ODE -, each molecule having an 18 carbon chain). This is not anomalous in the colloidal synthesis of inorganic NCs, but what is peculiar to perovskite NCs is their instability in polar solvents, which makes cleaning of the sample rather difficult. 5,6,26 Therefore, NCs are typically centrifuged without antisolvent and redispersed in toluene after discarding the supernatant. 5,18 This procedure leads to a poor cleaning efficiency, leaving residues of unbound ligands as well as ODE in the final solution, as also noted by others. 5,6,26 A large excess of these residues can result in a drop-cast film that remains partly fluid (gel-like) and not fully dried under ambient conditions. We show herein that annealing causes the removal of organic residues and part of the ligands at the surface of the NCs, which in turn affects the optoelectronic properties of the film. From 50 1C to 200 1C, a drop of the photoluminescence quantum yield (PLQY) is observed, accompanied by faster photoluminescence (PL) decay owing to the creation of trap states at the surface of
Solvent-free mechanochemical synthesis of phase-pure inorganic halide perovskites is investigated in depth revealing several beneficial and detrimental effects of ball-milling.
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