A nanomedicine, chemistry and tumor biology therapeutic recipe made @ UK-Portugal to defeat glioblastoma

Cláudia Martins; Catarina Barbosa; Marco Araújo; Stuart J. Smith; Maria Oliveira; Dimitrios Lamprou; Ruman Rahman; Jonathan W. Aylott; Bruno Sarmento

A nanomedicine, chemistry and tumor biology therapeutic recipe made @ UK-Portugal to defeat glioblastoma

Cláudia Martins, Catarina Barbosa, Marco Araújo, Stuart J. Smith, Maria Oliveira, Dimitrios Lamprou, Ruman Rahman, Jonathan W. Aylott, Bruno Sarmento

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Abstract

The 5-year survival of glioblastoma (GBM) patients is limited to a dismal
5%, highlighting the need to advance more effective therapies. GBM tissue abnormally overexpresses the L-type amino acid transporter 1 (LAT1), for which L-histidine (His) is an inexpensive and powerful targeting ligand. Thus, we propose the chemical modification of a conventional chemo-immunogenic drug, docetaxel, into a nanomedicine with surface-His (nano-DTX-His) to target GBM tissue via LAT1 adhesive binding and further augment localized cell death. Since nano-DTX-His cannot be used for IV therapies due its inability to cross the blood-brain barrier (BBB) per se, we further propose its modification with an
acid-cleavable Angiopep-2 layer (nano-DTX-His-clv-Angiopep2) to favor BBB
translocation. It is of important note that the choice of DTX is based on its IC50, which is around 20.000-times lower than the standard temozolomide (in https://www.cancerrxgene.org/).

Original language	English
Publication status	Accepted - 01 Sept 2021
Event	2021 UKICRS Virtual Symposium - Duration: 13 Oct 2021 → 13 Oct 2021 https://www.ukicrs.org/2021-virtual-symposium.html

Conference

Conference	2021 UKICRS Virtual Symposium
Period	13/10/2021 → 13/10/2021
Internet address	https://www.ukicrs.org/2021-virtual-symposium.html

Keywords

Nanomedicine
Microfluidics
TUMOR
Glioblastoma

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A nanomedicine, chemistry and tumor biology therapeutic recipe made @ UK-Portugal to defeat glioblastoma
Copyright 2021 the Author.
Accepted author manuscript, 116 KBLicence: Unspecified

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title = "A nanomedicine, chemistry and tumor biology therapeutic recipe made @ UK-Portugal to defeat glioblastoma",

abstract = "The 5-year survival of glioblastoma (GBM) patients is limited to a dismal5%, highlighting the need to advance more effective therapies. GBM tissue abnormally overexpresses the L-type amino acid transporter 1 (LAT1), for which L-histidine (His) is an inexpensive and powerful targeting ligand. Thus, we propose the chemical modification of a conventional chemo-immunogenic drug, docetaxel, into a nanomedicine with surface-His (nano-DTX-His) to target GBM tissue via LAT1 adhesive binding and further augment localized cell death. Since nano-DTX-His cannot be used for IV therapies due its inability to cross the blood-brain barrier (BBB) per se, we further propose its modification with anacid-cleavable Angiopep-2 layer (nano-DTX-His-clv-Angiopep2) to favor BBBtranslocation. It is of important note that the choice of DTX is based on its IC50, which is around 20.000-times lower than the standard temozolomide (in https://www.cancerrxgene.org/).",

keywords = "Nanomedicine, Microfluidics, TUMOR, Glioblastoma",

author = "Cl{\'a}udia Martins and Catarina Barbosa and Marco Ara{\'u}jo and Smith, {Stuart J.} and Maria Oliveira and Dimitrios Lamprou and Ruman Rahman and Aylott, {Jonathan W.} and Bruno Sarmento",

year = "2021",

month = sep,

day = "1",

language = "English",

note = "2021 UKICRS Virtual Symposium ; Conference date: 13-10-2021 Through 13-10-2021",

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TY - CONF

T1 - A nanomedicine, chemistry and tumor biology therapeutic recipe made @ UK-Portugal to defeat glioblastoma

AU - Martins, Cláudia

AU - Barbosa, Catarina

AU - Araújo, Marco

AU - Smith, Stuart J.

AU - Oliveira, Maria

AU - Lamprou, Dimitrios

AU - Rahman, Ruman

AU - Aylott, Jonathan W.

AU - Sarmento, Bruno

PY - 2021/9/1

Y1 - 2021/9/1

N2 - The 5-year survival of glioblastoma (GBM) patients is limited to a dismal5%, highlighting the need to advance more effective therapies. GBM tissue abnormally overexpresses the L-type amino acid transporter 1 (LAT1), for which L-histidine (His) is an inexpensive and powerful targeting ligand. Thus, we propose the chemical modification of a conventional chemo-immunogenic drug, docetaxel, into a nanomedicine with surface-His (nano-DTX-His) to target GBM tissue via LAT1 adhesive binding and further augment localized cell death. Since nano-DTX-His cannot be used for IV therapies due its inability to cross the blood-brain barrier (BBB) per se, we further propose its modification with anacid-cleavable Angiopep-2 layer (nano-DTX-His-clv-Angiopep2) to favor BBBtranslocation. It is of important note that the choice of DTX is based on its IC50, which is around 20.000-times lower than the standard temozolomide (in https://www.cancerrxgene.org/).

AB - The 5-year survival of glioblastoma (GBM) patients is limited to a dismal5%, highlighting the need to advance more effective therapies. GBM tissue abnormally overexpresses the L-type amino acid transporter 1 (LAT1), for which L-histidine (His) is an inexpensive and powerful targeting ligand. Thus, we propose the chemical modification of a conventional chemo-immunogenic drug, docetaxel, into a nanomedicine with surface-His (nano-DTX-His) to target GBM tissue via LAT1 adhesive binding and further augment localized cell death. Since nano-DTX-His cannot be used for IV therapies due its inability to cross the blood-brain barrier (BBB) per se, we further propose its modification with anacid-cleavable Angiopep-2 layer (nano-DTX-His-clv-Angiopep2) to favor BBBtranslocation. It is of important note that the choice of DTX is based on its IC50, which is around 20.000-times lower than the standard temozolomide (in https://www.cancerrxgene.org/).

KW - Nanomedicine

KW - Microfluidics

KW - TUMOR

KW - Glioblastoma

M3 - Abstract

T2 - 2021 UKICRS Virtual Symposium

Y2 - 13 October 2021 through 13 October 2021

ER -

A nanomedicine, chemistry and tumor biology therapeutic recipe made @ UK-Portugal to defeat glioblastoma

Abstract

Conference

Keywords

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Cite this