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Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length

Cell-penetrating peptides (CPPs) are commonly used substances enhancing the cellular uptake of various cargoes that do not easily cross the cellular membrane. CPPs can be either covalently bound directly to the cargo or they can be attached to a transporting system such as a polymer carrier together...

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Autores principales: Böhmová, Eliška, Pola, Robert, Pechar, Michal, Parnica, Jozef, Machová, Daniela, Janoušková, Olga, Etrych, Tomáš
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023232/
https://www.ncbi.nlm.nih.gov/pubmed/31936737
http://dx.doi.org/10.3390/pharmaceutics12010059
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author Böhmová, Eliška
Pola, Robert
Pechar, Michal
Parnica, Jozef
Machová, Daniela
Janoušková, Olga
Etrych, Tomáš
author_facet Böhmová, Eliška
Pola, Robert
Pechar, Michal
Parnica, Jozef
Machová, Daniela
Janoušková, Olga
Etrych, Tomáš
author_sort Böhmová, Eliška
collection PubMed
description Cell-penetrating peptides (CPPs) are commonly used substances enhancing the cellular uptake of various cargoes that do not easily cross the cellular membrane. CPPs can be either covalently bound directly to the cargo or they can be attached to a transporting system such as a polymer carrier together with the cargo. In this work, several CPP–polymer conjugates based on copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) with HIV-1 Tat peptide (TAT), a minimal sequence of penetratin (PEN), IRS-tag (RYIRS), and PTD4 peptide, and the two short hydrophobic peptides VPMLK and PFVYLI were prepared and characterized. Moreover, the biological efficacy of fluorescently labeled polymer carriers decorated with various CPPs was compared. The experiments revealed that the TAT–polymer conjugate and the PEN–polymer conjugate were internalized about 40 times and 15 times more efficiently than the control polymer, respectively. Incorporation of dodeca(ethylene glycol) spacer improved the cell penetration of both studied polymer–peptide conjugates compared to the corresponding spacer-free polymer conjugates, while the shorter tetra(ethylene glycol) spacer improved only the penetration of the TAT conjugate but it did not improve the penetration of the PEN conjugate. Finally, a significantly improved cytotoxic effect of the polymer conjugate containing anticancer drug pirarubicin and TAT attached via a dodeca(ethylene glycol) was observed when compared with the analogous polymer–pirarubicin conjugate without TAT.
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spelling pubmed-70232322020-03-12 Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length Böhmová, Eliška Pola, Robert Pechar, Michal Parnica, Jozef Machová, Daniela Janoušková, Olga Etrych, Tomáš Pharmaceutics Article Cell-penetrating peptides (CPPs) are commonly used substances enhancing the cellular uptake of various cargoes that do not easily cross the cellular membrane. CPPs can be either covalently bound directly to the cargo or they can be attached to a transporting system such as a polymer carrier together with the cargo. In this work, several CPP–polymer conjugates based on copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) with HIV-1 Tat peptide (TAT), a minimal sequence of penetratin (PEN), IRS-tag (RYIRS), and PTD4 peptide, and the two short hydrophobic peptides VPMLK and PFVYLI were prepared and characterized. Moreover, the biological efficacy of fluorescently labeled polymer carriers decorated with various CPPs was compared. The experiments revealed that the TAT–polymer conjugate and the PEN–polymer conjugate were internalized about 40 times and 15 times more efficiently than the control polymer, respectively. Incorporation of dodeca(ethylene glycol) spacer improved the cell penetration of both studied polymer–peptide conjugates compared to the corresponding spacer-free polymer conjugates, while the shorter tetra(ethylene glycol) spacer improved only the penetration of the TAT conjugate but it did not improve the penetration of the PEN conjugate. Finally, a significantly improved cytotoxic effect of the polymer conjugate containing anticancer drug pirarubicin and TAT attached via a dodeca(ethylene glycol) was observed when compared with the analogous polymer–pirarubicin conjugate without TAT. MDPI 2020-01-10 /pmc/articles/PMC7023232/ /pubmed/31936737 http://dx.doi.org/10.3390/pharmaceutics12010059 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Böhmová, Eliška
Pola, Robert
Pechar, Michal
Parnica, Jozef
Machová, Daniela
Janoušková, Olga
Etrych, Tomáš
Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length
title Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length
title_full Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length
title_fullStr Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length
title_full_unstemmed Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length
title_short Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length
title_sort polymer cancerostatics containing cell-penetrating peptides: internalization efficacy depends on peptide type and spacer length
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023232/
https://www.ncbi.nlm.nih.gov/pubmed/31936737
http://dx.doi.org/10.3390/pharmaceutics12010059
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