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DDC: 610 × Subject: nanoparticle ×

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    Graphene oxide functional nanohybrids with magnetic nanoparticles for improved vectorization of doxorubicin to neuroblastoma cells
    (Basel : MDPI AG, 2019) Lerra, L.; Farfalla, A.; Sanz, B.; Cirillo, G.; Vittorio, O.; Voli, F.; Grand, M.L.; Curcio, M.; Nicoletta, F.P.; Dubrovska, A.; Hampel, S.; Iemma, F.; Goya, G.F.
    With the aim to obtain a site-specific doxorubicin (DOX) delivery in neuroblastoma SH-SY5Y cells, we designed an hybrid nanocarrier combining graphene oxide (GO) and magnetic iron oxide nanoparticles (MNPs), acting as core elements, and a curcumin–human serum albumin conjugate as functional coating. The nanohybrid, synthesized by redox reaction between the MNPs@GO system and albumin bioconjugate, consisted of MNPs@GO nanosheets homogeneously coated by the bioconjugate as verified by SEM investigations. Drug release experiments showed a pH-responsive behavior with higher release amounts in acidic (45% at pH 5.0) vs. neutral (28% at pH 7.4) environments. Cell internalization studies proved the presence of nanohybrid inside SH-SY5Y cytoplasm. The improved efficacy obtained in viability assays is given by the synergy of functional coating and MNPs constituting the nanohybrids: while curcumin moieties were able to keep low DOX cytotoxicity levels (at concentrations of 0.44–0.88 µM), the presence of MNPs allowed remote actuation on the nanohybrid by a magnetic field, increasing the dose delivered at the target site.
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    Silk nanoparticles: proof of lysosomotropic anticancer drug delivery at single-cell resolution
    (Abingdon : Taylor & Francis Group, 2017) Totten, John D.; Wongpinyochit, Thidarat; Seib, F. Philipp
    Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release. MCF-7 human breast cancer cells endocytosed and trafficked drug-loaded native and PEGylated silk nanoparticles (∼100 nm in diameter) to lysosomes, with subsequent drug release from the respective carriers and nuclear translocation within 5 h of dosing. A combination of low pH and enzymatic degradation facilitated drug release from the silk nanoparticles; perturbation of the acidic lysosomal pH and inhibition of serine, cysteine and threonine proteases resulted in a 42% ± 2.2% and 33% ± 3% reduction in nuclear-associated drug accumulation for native and PEGylated silk nanoparticles, respectively. Overall, this study demonstrates the importance of lysosomal activity for anticancer drug release from silk nanoparticles, thereby providing direct evidence for lysosomotropic drug delivery in live cells.