Homotypic targeting and drug delivery in glioblastoma cells through cell membrane-coated boron nitride nanotubes

Pasquale, Daniele De; Marino, Attilio; Tapeinos, Christos; Pucci, Carlotta; Rocchiccioli, Silvia; Michelucci, Elena; Finamore, Francesco; McDonnell, Liam A.; Scarpellini, Alice; Lauciello, Simone; Prato, Mirko; Larrañaga, Aitor; Drago, Filippo; Ciofani, Gianni

doi:10.1016/j.matdes.2020.108742

Cited by 75 publications

(81 citation statements)

References 91 publications

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“…Drug-based nanomedicine approaches have been recently exploited to kill GB cells [ 64 , 65 , 66 , 67 ]. Apart from those studies, our results suggest that PEI modification imparts a new, intrinsic property to nanoparticles in killing of GSCs without any additional anti-cancer drug treatment when cultured specifically under stem cell conditions.…”

Section: Discussionmentioning

confidence: 99%

Circumventing Drug Treatment? Intrinsic Lethal Effects of Polyethyleneimine (PEI)-Functionalized Nanoparticles on Glioblastoma Cells Cultured in Stem Cell Conditions

Prabhakar

Merisaari

Joncour

et al. 2021

Cancers

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Glioblastoma (GB) is the most frequent malignant tumor originating from the central nervous system. Despite breakthroughs in treatment modalities for other cancer types, GB remains largely irremediable due to the high degree of intratumoral heterogeneity, infiltrative growth, and intrinsic resistance towards multiple treatments. A sub-population of GB cells, glioblastoma stem cells (GSCs), act as a reservoir of cancer-initiating cells and consequently, constitute a significant challenge for successful therapy. In this study, we discovered that PEI surface-functionalized mesoporous silica nanoparticles (PEI-MSNs), without any anti-cancer drug, very potently kill multiple GSC lines cultured in stem cell conditions. Very importantly, PEI-MSNs did not affect the survival of established GB cells, nor other types of cancer cells cultured in serum-containing medium, even at 25 times higher doses. PEI-MSNs did not induce any signs of apoptosis or autophagy. Instead, as a potential explanation for their lethality under stem cell culture conditions, we demonstrate that the internalized PEI-MSNs accumulated inside lysosomes, subsequently causing a rupture of the lysosomal membranes. We also demonstrate blood–brain-barrier (BBB) permeability of the PEI-MSNs in vitro and in vivo. Taking together the recent indications for the vulnerability of GSCs for lysosomal targeting and the lethality of the PEI-MSNs on GSCs cultured under stem cell culture conditions, the results enforce in vivo testing of the therapeutic impact of PEI-functionalized nanoparticles in faithful preclinical GB models.

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Section: Discussionmentioning

confidence: 99%

Circumventing Drug Treatment? Intrinsic Lethal Effects of Polyethyleneimine (PEI)-Functionalized Nanoparticles on Glioblastoma Cells Cultured in Stem Cell Conditions

Prabhakar

Merisaari

Joncour

et al. 2021

Cancers

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“…Therefore, our data confirm this finding and strengthens the theory of the lysosomal vulnerability of GSCs. Our results further suggest that PEI modification imparts a new, inherent property to nanoparticles in selective killing of GSCs without any additional anti-cancer drug treatment, which is contrary to recently reported drug based nanomedicinal approaches to eradicate GB [64][65][66][67]. We also demonstrated the potential of the PEI-MSNs to be directly delivered to GSCs via intranasal or intravenous administration for the successful eradication of GSCs in vivo.…”

Section: Pei-msns Cross the Neurovascular Unit In Vitro And In Vivomentioning

confidence: 46%

Circumventing drug treatment? Polyethylenimine functionalized nanoparticles inherently and selectively kill patient-derived glioblastoma stem cells

Prabhakar

Merisaari

Joncour

et al. 2020

Preprint

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Glioblastoma (GB) is the most frequent malignant tumor originating from the central nervous system. Despite breakthroughs in treatment modalities for other cancer types, GB remains largely irremediable due to its high degree of intratumoral heterogeneity, infiltrative growth, and intrinsic resistance towards multiple treatments. These resistant and aggressive sub-populations of GBs including the glioblastoma stem cells (GSCs) can circumvent treatment. GSCs act as a reservoir of cancer-initiating cells; they are a major challenge for successful therapy. We have discovered, as opposed to well-reported anti-cancer drug based therapeutical approach for GB therapy, the role of polyethylenimine (PEI) in inducing selective death of patient-derived GSCs via lysosomal membrane rupturing. Even at very low doses (1 ug/ml), PEI surface-functionalized mesoporous silica nanoparticles (PEI-MSNs), without any additional anti-cancer drug, very potently and selectively killed multiple GSC lines. Very importantly, PEI-MSNs did not affect the survival of well-established GB cells, or other type of cancer cells even at 25x higher doses. Remarkably, any sign of predominant cell death pathways such as apoptosis and autophagy was absent. Instead, as a potential explanation for their GSC selective killing function, we demonstrate that the internalized PEI-MSNs accumulated inside the lysosomes, subsequently causing a rupture of the vulnerable lysosomal membranes, exclusively in GSCs. As a further evaluation, we observed blood-brain-barrier (BBB) permeability of these PEI-MSNs in vitro and in vivo. Taking together the recent indications for the vulnerability of GSCs for lysosomal targeting, and GSC selectivity of the PEI-MSNs described here, the results suggest that PEI-functionalized nanoparticles could have a potential role in the eradication of GSCs.

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“…The nanoplatform exhibited strong potency for tumor treatment in vivo and magnetic resonance imaging (MRI). Owing to the homotypic recognition of GBM cells, Pasquale’s group exhibited a novel drug delivery system with enhanced targeting features that Dox was loaded in boron nitride nanotubes after which coated with GBM cell membranes (Dox-CM-BNNTs) 83 . In both in vitro multi-cellular culture and dynamic model, Dox-CM-BNNTs presented significant homotypic targeting and selective death in U87 MG cells while no obvious side-effect showed in normal cells.…”

Section: Cell Membrane Vectorsmentioning

confidence: 99%

“…In both in vitro multi-cellular culture and dynamic model, Dox-CM-BNNTs presented significant homotypic targeting and selective death in U87 MG cells while no obvious side-effect showed in normal cells. The excellent internalization efficiency of U87 MG cells can be explained by GBM cell membranes surface protein recognition that triggers mutual interactions in homotypic membranes through multiple internalization pathways 83 , 84 . In another research, Liu et al 85 successfully constructed a core-shell nanostructure for prostate cancer (PC) therapy where MSNs were leveraged as the core to load Dox, CaCO 3 interlayer as sheddable pH-sensitive gatekeepers to sustain drug release, and LNCaP-AI prostate CCM as the outermost layer (shorten as Dox/MSNs@CaCO 3 @CM) to enhance tumoritropic accumulation.…”

Section: Cell Membrane Vectorsmentioning

confidence: 99%

Recent progress in targeted delivery vectors based on biomimetic nanoparticles

Chen

Hong

Ren

et al. 2021

Sig Transduct Target Ther

142

132

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Over the past decades, great interest has been given to biomimetic nanoparticles (BNPs) since the rise of targeted drug delivery systems and biomimetic nanotechnology. Biological vectors including cell membranes, extracellular vesicles (EVs), and viruses are considered promising candidates for targeted delivery owing to their biocompatibility and biodegradability. BNPs, the integration of biological vectors and functional agents, are anticipated to load cargos or camouflage synthetic nanoparticles to achieve targeted delivery. Despite their excellent intrinsic properties, natural vectors are deliberately modified to endow multiple functions such as good permeability, improved loading capability, and high specificity. Through structural modification and transformation of the vectors, they are pervasively utilized as more effective vehicles that can deliver contrast agents, chemotherapy drugs, nucleic acids, and genes to target sites for refractory disease therapy. This review summarizes recent advances in targeted delivery vectors based on cell membranes, EVs, and viruses, highlighting the potential applications of BNPs in the fields of biomedical imaging and therapy industry, as well as discussing the possibility of clinical translation and exploitation trend of these BNPs.

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Homotypic targeting and drug delivery in glioblastoma cells through cell membrane-coated boron nitride nanotubes

Cited by 75 publications

References 91 publications

Circumventing Drug Treatment? Intrinsic Lethal Effects of Polyethyleneimine (PEI)-Functionalized Nanoparticles on Glioblastoma Cells Cultured in Stem Cell Conditions

Circumventing Drug Treatment? Intrinsic Lethal Effects of Polyethyleneimine (PEI)-Functionalized Nanoparticles on Glioblastoma Cells Cultured in Stem Cell Conditions

Circumventing drug treatment? Polyethylenimine functionalized nanoparticles inherently and selectively kill patient-derived glioblastoma stem cells

Recent progress in targeted delivery vectors based on biomimetic nanoparticles

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