Cargando…

Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo

Blocking the PD-1/PD-L1 pathway can diminish immunosuppression and enhance anticancer immunity. PD-1/PD-L1 blockade can be realized by aptamers, which have good biocompatibility and can be synthesized in quantity economically. For in vivo applications, aptamers need to evade renal clearance and nucl...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Ting, Yao, Fengjiao, An, Yacong, Li, Xundou, Duan, Jinhong, Yang, Xian-Da
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921949/
https://www.ncbi.nlm.nih.gov/pubmed/33670583
http://dx.doi.org/10.3390/molecules26041067
_version_ 1783658576483450880
author Li, Ting
Yao, Fengjiao
An, Yacong
Li, Xundou
Duan, Jinhong
Yang, Xian-Da
author_facet Li, Ting
Yao, Fengjiao
An, Yacong
Li, Xundou
Duan, Jinhong
Yang, Xian-Da
author_sort Li, Ting
collection PubMed
description Blocking the PD-1/PD-L1 pathway can diminish immunosuppression and enhance anticancer immunity. PD-1/PD-L1 blockade can be realized by aptamers, which have good biocompatibility and can be synthesized in quantity economically. For in vivo applications, aptamers need to evade renal clearance and nuclease digestion. Here we investigated whether DNA nanostructures could be used to enhance the function of PD-L1 aptamers. Four PD-L1 aptamers (Apt) were built into a Holliday Junction (HJ) to form a tetravalent DNA nanostructure (Apt-HJ). The average size of Apt-HJ was 13.22 nm, which was above the threshold for renal clearance. Apt-HJ also underwent partial phosphorothioate modification and had improved nuclease resistance. Compared with the monovalent PD-L1 aptamer, the tetravalent Apt-HJ had stronger affinity to CT26 colon cancer cells. Moreover, Apt-HJ markedly boosted the antitumor efficacy in vivo vs. free PD-L1 aptamers without raising systemic toxicity. The results indicate that multiple aptamers attached to a DNA nanostructure may significantly improve the function of PD-L1 aptamers in vivo.
format Online
Article
Text
id pubmed-7921949
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79219492021-03-03 Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo Li, Ting Yao, Fengjiao An, Yacong Li, Xundou Duan, Jinhong Yang, Xian-Da Molecules Article Blocking the PD-1/PD-L1 pathway can diminish immunosuppression and enhance anticancer immunity. PD-1/PD-L1 blockade can be realized by aptamers, which have good biocompatibility and can be synthesized in quantity economically. For in vivo applications, aptamers need to evade renal clearance and nuclease digestion. Here we investigated whether DNA nanostructures could be used to enhance the function of PD-L1 aptamers. Four PD-L1 aptamers (Apt) were built into a Holliday Junction (HJ) to form a tetravalent DNA nanostructure (Apt-HJ). The average size of Apt-HJ was 13.22 nm, which was above the threshold for renal clearance. Apt-HJ also underwent partial phosphorothioate modification and had improved nuclease resistance. Compared with the monovalent PD-L1 aptamer, the tetravalent Apt-HJ had stronger affinity to CT26 colon cancer cells. Moreover, Apt-HJ markedly boosted the antitumor efficacy in vivo vs. free PD-L1 aptamers without raising systemic toxicity. The results indicate that multiple aptamers attached to a DNA nanostructure may significantly improve the function of PD-L1 aptamers in vivo. MDPI 2021-02-18 /pmc/articles/PMC7921949/ /pubmed/33670583 http://dx.doi.org/10.3390/molecules26041067 Text en © 2021 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
Li, Ting
Yao, Fengjiao
An, Yacong
Li, Xundou
Duan, Jinhong
Yang, Xian-Da
Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo
title Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo
title_full Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo
title_fullStr Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo
title_full_unstemmed Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo
title_short Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo
title_sort novel complex of pd-l1 aptamer and holliday junction enhances antitumor efficacy in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921949/
https://www.ncbi.nlm.nih.gov/pubmed/33670583
http://dx.doi.org/10.3390/molecules26041067
work_keys_str_mv AT liting novelcomplexofpdl1aptamerandhollidayjunctionenhancesantitumorefficacyinvivo
AT yaofengjiao novelcomplexofpdl1aptamerandhollidayjunctionenhancesantitumorefficacyinvivo
AT anyacong novelcomplexofpdl1aptamerandhollidayjunctionenhancesantitumorefficacyinvivo
AT lixundou novelcomplexofpdl1aptamerandhollidayjunctionenhancesantitumorefficacyinvivo
AT duanjinhong novelcomplexofpdl1aptamerandhollidayjunctionenhancesantitumorefficacyinvivo
AT yangxianda novelcomplexofpdl1aptamerandhollidayjunctionenhancesantitumorefficacyinvivo