Cargando…

Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer

In this study, the novel carrier materials were screened to structure targeting nano-micelles (named ‘nano-dandelion’) for synchronous delivery of curcumin (Cur) and baicalin (Bai), which could effectively overcome the tumor resistance. Mannose (Man) was found to bind better to CD206 receptors on th...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Bingjie, Zhang, Wei, Zhou, Xiudi, Liu, Mengna, Hou, Xiaoya, Cheng, Ziting, Chen, Daquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896416/
https://www.ncbi.nlm.nih.gov/pubmed/31777307
http://dx.doi.org/10.1080/10717544.2019.1693707
_version_ 1783476774281150464
author Wang, Bingjie
Zhang, Wei
Zhou, Xiudi
Liu, Mengna
Hou, Xiaoya
Cheng, Ziting
Chen, Daquan
author_facet Wang, Bingjie
Zhang, Wei
Zhou, Xiudi
Liu, Mengna
Hou, Xiaoya
Cheng, Ziting
Chen, Daquan
author_sort Wang, Bingjie
collection PubMed
description In this study, the novel carrier materials were screened to structure targeting nano-micelles (named ‘nano-dandelion’) for synchronous delivery of curcumin (Cur) and baicalin (Bai), which could effectively overcome the tumor resistance. Mannose (Man) was found to bind better to CD206 receptors on the surface of tumor-associated macrophages (TAMs), thereby increasing the number of nano-dandelion engulfed by TAMs. Furthermore, oligomeric hyaluronic acid (oHA) was able to target CD44 receptors, resulting in recruitment of a higher number of nano-dandelion to locate and engulf tumor cells. The disulfide bond (S–S) in 3,3′-dithiodipropionic acid (DA) could be broken by the high concentration of glutathione (GSH) in the tumor microenvironment (TME). Based on this, we selected DA to connect hydrophobic fragments (quercetin, Que) and oHA. A reduction-sensitive amphiphilic carrier material, quercetin–dithiodipropionic acid–oligomeric hyaluronic acid–mannose–ferulic acid (Que–S–S–oHA–Man–FA; QHMF) was fabricated and synthesized by (1)H NMR. Next, QHMF self-assembled into nano-dandelion, i.e. encapsulated Cur and Bai in water. Critical experimental conditions in the preparation process of nano-dandelion that could affect its final properties were explored. Nano-dandelion with a small particle size (121.0 ± 15 nm) and good normal distribution (PI = 0.129) could easily enter tumor tissue through vascular barrier. In addition, nano-dandelion with a suitable surface potential (–20.33 ± 4.02 mV) could remain stable for a long duration. Furthermore, good cellular penetration and tumor cytotoxicity of nano-dandelion were demonstrated through in vitro cellular studies. Finally, effective antitumor activity and reduced side effects were confirmed through in vivo antitumor experiments in A549 tumor-bearing nude mice.
format Online
Article
Text
id pubmed-6896416
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-68964162019-12-13 Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer Wang, Bingjie Zhang, Wei Zhou, Xiudi Liu, Mengna Hou, Xiaoya Cheng, Ziting Chen, Daquan Drug Deliv Research Article In this study, the novel carrier materials were screened to structure targeting nano-micelles (named ‘nano-dandelion’) for synchronous delivery of curcumin (Cur) and baicalin (Bai), which could effectively overcome the tumor resistance. Mannose (Man) was found to bind better to CD206 receptors on the surface of tumor-associated macrophages (TAMs), thereby increasing the number of nano-dandelion engulfed by TAMs. Furthermore, oligomeric hyaluronic acid (oHA) was able to target CD44 receptors, resulting in recruitment of a higher number of nano-dandelion to locate and engulf tumor cells. The disulfide bond (S–S) in 3,3′-dithiodipropionic acid (DA) could be broken by the high concentration of glutathione (GSH) in the tumor microenvironment (TME). Based on this, we selected DA to connect hydrophobic fragments (quercetin, Que) and oHA. A reduction-sensitive amphiphilic carrier material, quercetin–dithiodipropionic acid–oligomeric hyaluronic acid–mannose–ferulic acid (Que–S–S–oHA–Man–FA; QHMF) was fabricated and synthesized by (1)H NMR. Next, QHMF self-assembled into nano-dandelion, i.e. encapsulated Cur and Bai in water. Critical experimental conditions in the preparation process of nano-dandelion that could affect its final properties were explored. Nano-dandelion with a small particle size (121.0 ± 15 nm) and good normal distribution (PI = 0.129) could easily enter tumor tissue through vascular barrier. In addition, nano-dandelion with a suitable surface potential (–20.33 ± 4.02 mV) could remain stable for a long duration. Furthermore, good cellular penetration and tumor cytotoxicity of nano-dandelion were demonstrated through in vitro cellular studies. Finally, effective antitumor activity and reduced side effects were confirmed through in vivo antitumor experiments in A549 tumor-bearing nude mice. Taylor & Francis 2019-11-28 /pmc/articles/PMC6896416/ /pubmed/31777307 http://dx.doi.org/10.1080/10717544.2019.1693707 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Bingjie
Zhang, Wei
Zhou, Xiudi
Liu, Mengna
Hou, Xiaoya
Cheng, Ziting
Chen, Daquan
Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
title Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
title_full Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
title_fullStr Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
title_full_unstemmed Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
title_short Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
title_sort development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896416/
https://www.ncbi.nlm.nih.gov/pubmed/31777307
http://dx.doi.org/10.1080/10717544.2019.1693707
work_keys_str_mv AT wangbingjie developmentofdualtargetednanodandelionbasedonanoligomerichyaluronicacidpolymertargetingtumorassociatedmacrophagesforcombinationtherapyofnonsmallcelllungcancer
AT zhangwei developmentofdualtargetednanodandelionbasedonanoligomerichyaluronicacidpolymertargetingtumorassociatedmacrophagesforcombinationtherapyofnonsmallcelllungcancer
AT zhouxiudi developmentofdualtargetednanodandelionbasedonanoligomerichyaluronicacidpolymertargetingtumorassociatedmacrophagesforcombinationtherapyofnonsmallcelllungcancer
AT liumengna developmentofdualtargetednanodandelionbasedonanoligomerichyaluronicacidpolymertargetingtumorassociatedmacrophagesforcombinationtherapyofnonsmallcelllungcancer
AT houxiaoya developmentofdualtargetednanodandelionbasedonanoligomerichyaluronicacidpolymertargetingtumorassociatedmacrophagesforcombinationtherapyofnonsmallcelllungcancer
AT chengziting developmentofdualtargetednanodandelionbasedonanoligomerichyaluronicacidpolymertargetingtumorassociatedmacrophagesforcombinationtherapyofnonsmallcelllungcancer
AT chendaquan developmentofdualtargetednanodandelionbasedonanoligomerichyaluronicacidpolymertargetingtumorassociatedmacrophagesforcombinationtherapyofnonsmallcelllungcancer