Cargando…

Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer

Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this...

Descripción completa

Detalles Bibliográficos
Autores principales: Ni, Jiang, Mi, Yuanyuan, Wang, Bei, Zhu, Yuting, Ding, Yang, Ding, Yongjuan, Li, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404723/
https://www.ncbi.nlm.nih.gov/pubmed/36004889
http://dx.doi.org/10.3390/bioengineering9080363
_version_ 1784773702414499840
author Ni, Jiang
Mi, Yuanyuan
Wang, Bei
Zhu, Yuting
Ding, Yang
Ding, Yongjuan
Li, Xia
author_facet Ni, Jiang
Mi, Yuanyuan
Wang, Bei
Zhu, Yuting
Ding, Yang
Ding, Yongjuan
Li, Xia
author_sort Ni, Jiang
collection PubMed
description Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this work, urinary exosomes (UEs) with high expression of CD9 and CD47 were extracted from breast cancer patients by a non−invasive method. Here, a nanotechnology approach is reported for tumor homologous targeting via CD9 and phagocytosis escape via CD47 through UE−coated poly (2−ethyl−2−oxazoline)−poly (D, L−lactide) (PEOz−PLA) nanoparticles (UEPP NPs). The cytotoxic agent doxorubicin (DOX)−loaded UEPP (UEPP−D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment. In vitro experiments revealed that UEPP−D NPs exhibited significantly improved cellular uptake, cytotoxicity, and apoptosis in MCF−7 cell lines as compared to DOX−loaded PEOz−PLA nanoparticles (PP−D NPs) and free DOX. More importantly, anti−phagocytosis and pharmacokinetic studies confirmed that UEPP−D NPs had superior immune escape ability and significantly prolonged the drug’s bloodstream circulation in vivo. Finally, UEPP−D NPs showed a markedly higher antitumor efficacy and lower side−toxicity in MCF−7 tumor bearing nude mice model. Thus, this versatile nano−system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment.
format Online
Article
Text
id pubmed-9404723
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94047232022-08-26 Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer Ni, Jiang Mi, Yuanyuan Wang, Bei Zhu, Yuting Ding, Yang Ding, Yongjuan Li, Xia Bioengineering (Basel) Article Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this work, urinary exosomes (UEs) with high expression of CD9 and CD47 were extracted from breast cancer patients by a non−invasive method. Here, a nanotechnology approach is reported for tumor homologous targeting via CD9 and phagocytosis escape via CD47 through UE−coated poly (2−ethyl−2−oxazoline)−poly (D, L−lactide) (PEOz−PLA) nanoparticles (UEPP NPs). The cytotoxic agent doxorubicin (DOX)−loaded UEPP (UEPP−D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment. In vitro experiments revealed that UEPP−D NPs exhibited significantly improved cellular uptake, cytotoxicity, and apoptosis in MCF−7 cell lines as compared to DOX−loaded PEOz−PLA nanoparticles (PP−D NPs) and free DOX. More importantly, anti−phagocytosis and pharmacokinetic studies confirmed that UEPP−D NPs had superior immune escape ability and significantly prolonged the drug’s bloodstream circulation in vivo. Finally, UEPP−D NPs showed a markedly higher antitumor efficacy and lower side−toxicity in MCF−7 tumor bearing nude mice model. Thus, this versatile nano−system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment. MDPI 2022-08-03 /pmc/articles/PMC9404723/ /pubmed/36004889 http://dx.doi.org/10.3390/bioengineering9080363 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ni, Jiang
Mi, Yuanyuan
Wang, Bei
Zhu, Yuting
Ding, Yang
Ding, Yongjuan
Li, Xia
Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer
title Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer
title_full Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer
title_fullStr Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer
title_full_unstemmed Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer
title_short Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer
title_sort naturally equipped urinary exosomes coated poly (2−ethyl−2−oxazoline)−poly (d, l−lactide) nanocarriers for the pre−clinical translation of breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404723/
https://www.ncbi.nlm.nih.gov/pubmed/36004889
http://dx.doi.org/10.3390/bioengineering9080363
work_keys_str_mv AT nijiang naturallyequippedurinaryexosomescoatedpoly2ethyl2oxazolinepolydllactidenanocarriersforthepreclinicaltranslationofbreastcancer
AT miyuanyuan naturallyequippedurinaryexosomescoatedpoly2ethyl2oxazolinepolydllactidenanocarriersforthepreclinicaltranslationofbreastcancer
AT wangbei naturallyequippedurinaryexosomescoatedpoly2ethyl2oxazolinepolydllactidenanocarriersforthepreclinicaltranslationofbreastcancer
AT zhuyuting naturallyequippedurinaryexosomescoatedpoly2ethyl2oxazolinepolydllactidenanocarriersforthepreclinicaltranslationofbreastcancer
AT dingyang naturallyequippedurinaryexosomescoatedpoly2ethyl2oxazolinepolydllactidenanocarriersforthepreclinicaltranslationofbreastcancer
AT dingyongjuan naturallyequippedurinaryexosomescoatedpoly2ethyl2oxazolinepolydllactidenanocarriersforthepreclinicaltranslationofbreastcancer
AT lixia naturallyequippedurinaryexosomescoatedpoly2ethyl2oxazolinepolydllactidenanocarriersforthepreclinicaltranslationofbreastcancer