Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Bo Wu,1,2,* Shu-Ting Lu,1,* Liu-Jie Zhang,2 Ren-Xi Zhuo,2 Hai-Bo Xu,1 Shi-Wen Huang2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People’s Republic of Chi...

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Autores principales: Wu B, Lu S, Zhang L, Zhuo RX, Xu HB, Huang SW
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:3ce1ce16bb794907aed876199e5906422021-12-02T01:46:43ZCodelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment1178-2013https://doaj.org/article/3ce1ce16bb794907aed876199e5906422017-03-01T00:00:00Zhttps://www.dovepress.com/codelivery-of-doxorubicin-and-triptolide-with-reduction-sensitive-lipi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Bo Wu,1,2,* Shu-Ting Lu,1,* Liu-Jie Zhang,2 Ren-Xi Zhuo,2 Hai-Bo Xu,1 Shi-Wen Huang2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid–polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), soybean lecithin, and poly(d,l-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment. Keywords: triptolide, codelivery, reduction sensitive, synergistic effectWu BLu SZhang LZhuo RXXu HBHuang SWDove Medical PressarticleTriptolideCo-deliveryreduction-sensitivesynergistic effectMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1853-1862 (2017)
institution DOAJ
collection DOAJ
language EN
topic Triptolide
Co-delivery
reduction-sensitive
synergistic effect
Medicine (General)
R5-920
spellingShingle Triptolide
Co-delivery
reduction-sensitive
synergistic effect
Medicine (General)
R5-920
Wu B
Lu S
Zhang L
Zhuo RX
Xu HB
Huang SW
Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment
description Bo Wu,1,2,* Shu-Ting Lu,1,* Liu-Jie Zhang,2 Ren-Xi Zhuo,2 Hai-Bo Xu,1 Shi-Wen Huang2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid–polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), soybean lecithin, and poly(d,l-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment. Keywords: triptolide, codelivery, reduction sensitive, synergistic effect
format article
author Wu B
Lu S
Zhang L
Zhuo RX
Xu HB
Huang SW
author_facet Wu B
Lu S
Zhang L
Zhuo RX
Xu HB
Huang SW
author_sort Wu B
title Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment
title_short Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment
title_full Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment
title_fullStr Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment
title_full_unstemmed Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment
title_sort codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/3ce1ce16bb794907aed876199e590642
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