Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1

Glioblastoma (GBM) is the most prevalent primary brain cancer in the pediatric and adult population. It is known as an untreatable tumor in urgent need of new therapeutic approaches. The objective of this work was to develop multifunctional nanomedicines to treat GBM in clinical practice using combi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rameshwar Patil, Tao Sun, Mohammad Harun Rashid, Liron L. Israel, Arshia Ramesh, Saya Davani, Keith L. Black, Alexander V. Ljubimov, Eggehard Holler, Julia Y. Ljubimova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	multifunctional drugs blood–brain barrier receptor-mediated transcytosis brain tumor delivery peptides nanocarriers Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/91053559e30d44f3896a6b91476c46a4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:91053559e30d44f3896a6b91476c46a4
record_format	dspace
spelling	oai:doaj.org-article:91053559e30d44f3896a6b91476c46a42021-11-25T18:30:39ZMultifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-110.3390/nano111128922079-4991https://doaj.org/article/91053559e30d44f3896a6b91476c46a42021-10-01T00:00:00Zhttps://www.mdpi.com/2079-4991/11/11/2892https://doaj.org/toc/2079-4991Glioblastoma (GBM) is the most prevalent primary brain cancer in the pediatric and adult population. It is known as an untreatable tumor in urgent need of new therapeutic approaches. The objective of this work was to develop multifunctional nanomedicines to treat GBM in clinical practice using combination therapy for several targets. We developed multifunctional nanopolymers (MNPs) based on a naturally derived biopolymer, poly(β-L-malic) acid, which are suitable for central nervous system (CNS) treatment. These MNPs contain several anticancer functional moieties with the capacity of crossing the blood–brain barrier (BBB), targeting GBM cells and suppressing two important molecular markers, tyrosine kinase transmembrane receptors EGFR/EGFRvIII and c-Myc nuclear transcription factor. The reproducible syntheses of MNPs where monoclonal antibodies are replaced with AP-2 peptide for effective BBB delivery were presented. The active anticancer inhibitors of mRNA/protein syntheses were Morpholino antisense oligonucleotides (AONs). Two ways of covalent AON-polymer attachments with and without disulfide bonds were explored. These MNPs bearing AONs to <i>EGFR</i>/<i>EGFRvIII</i> and <i>c-Myc</i>, as well as in a combination with the polymer-attached checkpoint inhibitor anti-PD-1 antibody, orchestrated a multi-pronged attack on intracranial mouse GBM to successfully block tumor growth and significantly increase survival of brain tumor-bearing animals.Rameshwar PatilTao SunMohammad Harun RashidLiron L. IsraelArshia RameshSaya DavaniKeith L. BlackAlexander V. LjubimovEggehard HollerJulia Y. LjubimovaMDPI AGarticlemultifunctional drugsblood–brain barrierreceptor-mediated transcytosisbrain tumordelivery peptidesnanocarriersChemistryQD1-999ENNanomaterials, Vol 11, Iss 2892, p 2892 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	multifunctional drugs blood–brain barrier receptor-mediated transcytosis brain tumor delivery peptides nanocarriers Chemistry QD1-999
spellingShingle	multifunctional drugs blood–brain barrier receptor-mediated transcytosis brain tumor delivery peptides nanocarriers Chemistry QD1-999 Rameshwar Patil Tao Sun Mohammad Harun Rashid Liron L. Israel Arshia Ramesh Saya Davani Keith L. Black Alexander V. Ljubimov Eggehard Holler Julia Y. Ljubimova Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1
description	Glioblastoma (GBM) is the most prevalent primary brain cancer in the pediatric and adult population. It is known as an untreatable tumor in urgent need of new therapeutic approaches. The objective of this work was to develop multifunctional nanomedicines to treat GBM in clinical practice using combination therapy for several targets. We developed multifunctional nanopolymers (MNPs) based on a naturally derived biopolymer, poly(β-L-malic) acid, which are suitable for central nervous system (CNS) treatment. These MNPs contain several anticancer functional moieties with the capacity of crossing the blood–brain barrier (BBB), targeting GBM cells and suppressing two important molecular markers, tyrosine kinase transmembrane receptors EGFR/EGFRvIII and c-Myc nuclear transcription factor. The reproducible syntheses of MNPs where monoclonal antibodies are replaced with AP-2 peptide for effective BBB delivery were presented. The active anticancer inhibitors of mRNA/protein syntheses were Morpholino antisense oligonucleotides (AONs). Two ways of covalent AON-polymer attachments with and without disulfide bonds were explored. These MNPs bearing AONs to <i>EGFR</i>/<i>EGFRvIII</i> and <i>c-Myc</i>, as well as in a combination with the polymer-attached checkpoint inhibitor anti-PD-1 antibody, orchestrated a multi-pronged attack on intracranial mouse GBM to successfully block tumor growth and significantly increase survival of brain tumor-bearing animals.
format	article
author	Rameshwar Patil Tao Sun Mohammad Harun Rashid Liron L. Israel Arshia Ramesh Saya Davani Keith L. Black Alexander V. Ljubimov Eggehard Holler Julia Y. Ljubimova
author_facet	Rameshwar Patil Tao Sun Mohammad Harun Rashid Liron L. Israel Arshia Ramesh Saya Davani Keith L. Black Alexander V. Ljubimov Eggehard Holler Julia Y. Ljubimova
author_sort	Rameshwar Patil
title	Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1
title_short	Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1
title_full	Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1
title_fullStr	Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1
title_full_unstemmed	Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1
title_sort	multifunctional nanopolymers for blood–brain barrier delivery and inhibition of glioblastoma growth through egfr/egfrviii, c-myc, and pd-1
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/91053559e30d44f3896a6b91476c46a4
work_keys_str_mv	AT rameshwarpatil multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT taosun multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT mohammadharunrashid multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT lironlisrael multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT arshiaramesh multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT sayadavani multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT keithlblack multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT alexandervljubimov multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT eggehardholler multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1 AT juliayljubimova multifunctionalnanopolymersforbloodbrainbarrierdeliveryandinhibitionofglioblastomagrowththroughegfregfrviiicmycandpd1
_version_	1718411090572869632

Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1

Ejemplares similares