Coating Nanoparticles with Plant-Produced Transferrin–Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells

Reuter, Lauri; Shahbazi, Mohammad‐Ali; Mäkilä, Ermei; Salonen, Jarno; Saberianfar, Reza; Menassa, Rima; Santos, Hélder A.; Joensuu, Jussi; Ritala, Anneli

doi:10.1021/acs.bioconjchem.7b00075

Cited by 31 publications

(19 citation statements)

References 51 publications

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“…For example, Tf has been widely explored as a targeting ligand for improving BBB penetration of nanocarriers such as micelles 46 , liposomes 47 , and polymersomes 48 . Coating of Tf on pSiNP through hydrophobic interactions was first described by Reuter et al 49 They observed that Tf modification enhanced the internalisation into breast cancer cells. In this work, we studied whether Tf conjugation on pSiNP surface could enhance the internalisation into GBM cancer cells.…”

Section: Discussionmentioning

confidence: 94%

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Sheykhzadeh

Luo

Peng

et al. 2020

Sci Rep

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Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@ pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.Glioblastoma multiforme (GBM) is the most prevalent and biologically aggressive type of primary brain tumour in adults 1 . Standard treatment is maximal surgical resection of a tumour followed by radiotherapy and temozolomide as an adjuvant chemotherapy 2 . Despite these advanced treatments, the survival rate of GBM patients is still less than 5% over five years, with a median overall survival of merely 15-23 months 3 . The factors that contribute to the high mortality are multifactorial. First and foremost, the diffuse invasion of GBM into brain parenchyma precludes complete surgical resection which leads to high recurrence 4 . Recurring GBM are usually multi-drug resistant, rendering chemotherapy ineffective 5 . On rare occasions, the high invasion and migration potential even leads to extracranial metastases 6 .The mechanisms of GBM invasion and migration are complex and encompasses the regulation of tumour microenvironment and of the molecular arrangement within the migrating GBM cells 7 . To enable migration across the small perivascular space, GBM cells have been shown to reduce their volume by releasing cytoplasmic fluid 8 . The reduction in cell size is particularly instrumental to GBM invasion into healthy brain tissue, since www.nature.com/scientificreports www.nature.com/scientificreports/ recombinant human Fibroblast Growth Factor basic (Gibco, PHG0024), and StemPro Neural Supplement (Gibco, A10508-01). The culture media also contained GlutaMAX (Gibco, 35050-061) and penicillin/streptomycin (Gibco, 15140-122). Cells were only used betwe...

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Section: Discussionmentioning

confidence: 94%

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Sheykhzadeh

Luo

Peng

et al. 2020

Sci Rep

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“…Rapid accumulation of biomass and easy transformation has made the BY-2 cells the most frequently used plant cell line for protein production ( Doran, 2013 ). Proteins ranging from antibodies, enzymes, and therapeutic to technical proteins ( Sakamoto et al, 2008 ; Kirchhoff et al, 2012 ; Reuter et al, 2017 ) have been successfully expressed in BY-2 cells. However, when it comes to industrial production, two factors must be specifically ensured: stability of the production host and the cost efficiency of the production process ( Kurppa et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Tobacco BY-2 Media Component Optimization for a Cost-Efficient Recombinant Protein Production

et al. 2018

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Plant cells constitute an attractive platform for production of recombinant proteins as more and more animal-free products and processes are desired. One of the challenges in using plant cells as production hosts has been the costs deriving from expensive culture medium components. In this work, the aim was to optimize the levels of most expensive components in the nutrient medium without compromising the accumulation of biomass and recombinant protein yields. Wild-type BY-2 culture and transgenic tobacco BY-2 expressing green fluorescent protein–Hydrophobin I (GFP-HFBI) fusion protein were used to determine the most inexpensive medium composition. One particularly high-accumulating BY-2 clone, named ‘Hulk,’ produced 1.1 ± 0.2 g/l GFP-HFBI in suspension and kept its high performance during prolonged subculturing. In addition, both cultures were successfully cryopreserved enabling truly industrial application of this plant cell host. With the optimized culture medium, 43–55% cost reduction with regard to biomass and up to 69% reduction with regard to recombinant protein production was achieved.

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“…In fact, size, shape, size distribution and zeta potential of colloidal nanoparticles can affect their fate after systemic injection, and modulate distributions through passive targeting. 19 − 22 Furthermore, surface properties, 23 − 25 and modifications, 26 − 28 of colloidal nanoparticles can affect their potentialities in therapy, control pharmacokinetic and biodistribution, and target selectively cells and tissues.…”

Section: Resultsmentioning

confidence: 99%

Cell Membrane-Based Nanoreactor To Mimic the Bio-Compartmentalization Strategy of a Cell

Balasubramanian

Poillucci

Correia

et al. 2018

ACS Biomater. Sci. Eng.

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Organelles of eukaryotic cells are structures made up of membranes, which carry out a majority of functions necessary for the surviving of the cell itself. Organelles also differentiate the prokaryotic and eukaryotic cells, and are arranged to form different compartments guaranteeing the activities for which eukaryotic cells are programmed. Cell membranes, containing organelles, are isolated from cancer cells and erythrocytes and used to form biocompatible and long-circulating ghost nanoparticles delivering payloads or catalyzing enzymatic reactions as nanoreactors. In this attempt, red blood cell membranes were isolated from erythrocytes, and engineered to form nanoerythrosomes (NERs) of 150 nm. The horseradish peroxidase, used as an enzyme model, was loaded inside the aqueous compartment of NERs, and its catalytic reaction with Resorufin was monitored. The resulting nanoreactor protected the enzyme from proteolytic degradation, and potentiated the enzymatic reaction in situ as demonstrated by maximal velocity (Vmax) and Michaelis constant (Km), thus suggesting the high catalytic activity of nanoreactors compared to the pure enzymes.

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Coating Nanoparticles with Plant-Produced Transferrin–Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells

Cited by 31 publications

References 51 publications

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Tobacco BY-2 Media Component Optimization for a Cost-Efficient Recombinant Protein Production

Cell Membrane-Based Nanoreactor To Mimic the Bio-Compartmentalization Strategy of a Cell

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