Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes

Mariarosa Mazza; Hassan Ahmad; Marilena Hadjidemetriou; Giulia Agliardi; Omar N Pathmanaban; Andrew T King; Brian W Bigger; Sandra Vranic; Kostas Kostarelos

doi:10.2217/nnm-2019-0298

Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes

Mariarosa Mazza, Hassan Ahmad, Marilena Hadjidemetriou, Giulia Agliardi, Omar N Pathmanaban, Andrew T King, Brian W Bigger, Sandra Vranic, Kostas Kostarelos

The Manchester Metropolitan University

Research output: Contribution to journal › Article › peer-review

Abstract

Aim: To develop a nonviral tool for the delivery of siRNA to brain tumor cells using peptide nanofibers (PNFs). Materials & methods: Uptake of PNFs was evaluated by confocal microscopy and flow cytometry. Gene silencing was determined by RT-qPCR and cell invasion assay. Results: PNFs enter phagocytic (BV-2) and nonphagocytic (U-87 MG) cells via endocytosis and passive translocation. siPLK1 delivered using PNFs reduced the expression of polo-like kinase 1 mRNA and induced cell death in a panel of immortalized and glioblastoma-derived stem cells. Moreover, targeting MMP2 using PNF:siMMP2 reduced the invasion capacity of U-87 MG cells. We show that stereotactic intra-tumoral administration of PNF:siPLK1 significantly extends the survival of tumor bearing mice comparing with the untreated tumor bearing animals. Conclusion: Our results suggest that this nanomedicine-based RNA interference approach deserves further investigation as a potential brain tumor therapeutic tool.

Original language	English
Pages (from-to)	3127-3142
Number of pages	16
Journal	nanomedicine
Volume	14
Issue number	24
Early online date	19 Dec 2019
DOIs	https://doi.org/10.2217/nnm-2019-0298 https://doi.org/10.2217/nnm-2019-0298
Publication status	Published - Dec 2019

Keywords

Animals
Brain Neoplasms/metabolism
Cell Cycle Proteins/genetics
Cell Line, Tumor
Cell Movement/genetics
Cell Proliferation/genetics
Flow Cytometry
Genetic Therapy/methods
Humans
Matrix Metalloproteinase 2/genetics
Mice
Mice, Nude
Microscopy, Confocal
Nanofibers/chemistry
Nanomedicine/methods
Peptides/chemistry
Protein-Serine-Threonine Kinases/genetics
Proto-Oncogene Proteins/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes",

abstract = "Aim: To develop a nonviral tool for the delivery of siRNA to brain tumor cells using peptide nanofibers (PNFs). Materials & methods: Uptake of PNFs was evaluated by confocal microscopy and flow cytometry. Gene silencing was determined by RT-qPCR and cell invasion assay. Results: PNFs enter phagocytic (BV-2) and nonphagocytic (U-87 MG) cells via endocytosis and passive translocation. siPLK1 delivered using PNFs reduced the expression of polo-like kinase 1 mRNA and induced cell death in a panel of immortalized and glioblastoma-derived stem cells. Moreover, targeting MMP2 using PNF:siMMP2 reduced the invasion capacity of U-87 MG cells. We show that stereotactic intra-tumoral administration of PNF:siPLK1 significantly extends the survival of tumor bearing mice comparing with the untreated tumor bearing animals. Conclusion: Our results suggest that this nanomedicine-based RNA interference approach deserves further investigation as a potential brain tumor therapeutic tool.",

keywords = "Animals, Brain Neoplasms/metabolism, Cell Cycle Proteins/genetics, Cell Line, Tumor, Cell Movement/genetics, Cell Proliferation/genetics, Flow Cytometry, Genetic Therapy/methods, Humans, Matrix Metalloproteinase 2/genetics, Mice, Mice, Nude, Microscopy, Confocal, Nanofibers/chemistry, Nanomedicine/methods, Peptides/chemistry, Protein-Serine-Threonine Kinases/genetics, Proto-Oncogene Proteins/genetics",

author = "Mariarosa Mazza and Hassan Ahmad and Marilena Hadjidemetriou and Giulia Agliardi and Pathmanaban, {Omar N} and King, {Andrew T} and Bigger, {Brian W} and Sandra Vranic and Kostas Kostarelos",

year = "2019",

month = dec,

doi = "10.2217/nnm-2019-0298",

language = "English",

volume = "14",

pages = "3127--3142",

journal = "nanomedicine",

issn = "1743-5889",

publisher = "Future Medicine ",

number = "24",

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TY - JOUR

T1 - Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes

AU - Mazza, Mariarosa

AU - Ahmad, Hassan

AU - Hadjidemetriou, Marilena

AU - Agliardi, Giulia

AU - Pathmanaban, Omar N

AU - King, Andrew T

AU - Bigger, Brian W

AU - Vranic, Sandra

AU - Kostarelos, Kostas

PY - 2019/12

Y1 - 2019/12

N2 - Aim: To develop a nonviral tool for the delivery of siRNA to brain tumor cells using peptide nanofibers (PNFs). Materials & methods: Uptake of PNFs was evaluated by confocal microscopy and flow cytometry. Gene silencing was determined by RT-qPCR and cell invasion assay. Results: PNFs enter phagocytic (BV-2) and nonphagocytic (U-87 MG) cells via endocytosis and passive translocation. siPLK1 delivered using PNFs reduced the expression of polo-like kinase 1 mRNA and induced cell death in a panel of immortalized and glioblastoma-derived stem cells. Moreover, targeting MMP2 using PNF:siMMP2 reduced the invasion capacity of U-87 MG cells. We show that stereotactic intra-tumoral administration of PNF:siPLK1 significantly extends the survival of tumor bearing mice comparing with the untreated tumor bearing animals. Conclusion: Our results suggest that this nanomedicine-based RNA interference approach deserves further investigation as a potential brain tumor therapeutic tool.

AB - Aim: To develop a nonviral tool for the delivery of siRNA to brain tumor cells using peptide nanofibers (PNFs). Materials & methods: Uptake of PNFs was evaluated by confocal microscopy and flow cytometry. Gene silencing was determined by RT-qPCR and cell invasion assay. Results: PNFs enter phagocytic (BV-2) and nonphagocytic (U-87 MG) cells via endocytosis and passive translocation. siPLK1 delivered using PNFs reduced the expression of polo-like kinase 1 mRNA and induced cell death in a panel of immortalized and glioblastoma-derived stem cells. Moreover, targeting MMP2 using PNF:siMMP2 reduced the invasion capacity of U-87 MG cells. We show that stereotactic intra-tumoral administration of PNF:siPLK1 significantly extends the survival of tumor bearing mice comparing with the untreated tumor bearing animals. Conclusion: Our results suggest that this nanomedicine-based RNA interference approach deserves further investigation as a potential brain tumor therapeutic tool.

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KW - Cell Cycle Proteins/genetics

KW - Cell Line, Tumor

KW - Cell Movement/genetics

KW - Cell Proliferation/genetics

KW - Flow Cytometry

KW - Genetic Therapy/methods

KW - Humans

KW - Matrix Metalloproteinase 2/genetics

KW - Mice

KW - Mice, Nude

KW - Microscopy, Confocal

KW - Nanofibers/chemistry

KW - Nanomedicine/methods

KW - Peptides/chemistry

KW - Protein-Serine-Threonine Kinases/genetics

KW - Proto-Oncogene Proteins/genetics

U2 - 10.2217/nnm-2019-0298

DO - 10.2217/nnm-2019-0298

M3 - Article

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SN - 1743-5889

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SP - 3127

EP - 3142

JO - nanomedicine

JF - nanomedicine

IS - 24

ER -

Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes

Abstract

Keywords

UN SDGs

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