Doxifluridine-based pharmacosomes delivering miR-122 as tumor microenvironments-activated nanoplatforms for synergistic treatment of hepatocellular carcinoma

Fangqin Xue; Xiao Lin; Zhixiong Cai; Xiaolong Liu; Yuan Ma; Ming Wu

doi:10.1016/j.colsurfb.2020.111367

Doxifluridine-based pharmacosomes delivering miR-122 as tumor microenvironments-activated nanoplatforms for synergistic treatment of hepatocellular carcinoma

Fangqin Xue, Xiao Lin, Zhixiong Cai, Xiaolong Liu, Yuan Ma^*, Ming Wu^*

^*Corresponding author for this work

Chinese Medicine - Teaching and Research Division

Research output: Contribution to journal › Journal article › peer-review

13 Citations (Scopus)

Abstract

A novel kind of anti-cancer pharmacosome (named NPC-D) derived from Doxifluridine (5′-DFUR) was described, which could be activated by tumor microenvironments (TMEs). The NPC-D with H₂O₂-sensitive linker was dispersed well in water and simultaneously interacted with nucleic acids including plasmids encoding miR-122 (p122) and EpCAM-targeted aptamer (ap1) via charge interaction and hydrogen bonding. The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of H₂O₂ and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment.

Original language	English
Article number	111367
Number of pages	9
Journal	Colloids and Surfaces B: Biointerfaces
Volume	197
DOIs	https://doi.org/10.1016/j.colsurfb.2020.111367
Publication status	Published - Jan 2021

User-Defined Keywords

EpCAM-targeted aptamer
miR-122
Pharmacosome
Synergistic anticancer effect
Tumor microenvironments

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.colsurfb.2020.111367

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title = "Doxifluridine-based pharmacosomes delivering miR-122 as tumor microenvironments-activated nanoplatforms for synergistic treatment of hepatocellular carcinoma",

abstract = "A novel kind of anti-cancer pharmacosome (named NPC-D) derived from Doxifluridine (5′-DFUR) was described, which could be activated by tumor microenvironments (TMEs). The NPC-D with H2O2-sensitive linker was dispersed well in water and simultaneously interacted with nucleic acids including plasmids encoding miR-122 (p122) and EpCAM-targeted aptamer (ap1) via charge interaction and hydrogen bonding. The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of H2O2 and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment.",

keywords = "EpCAM-targeted aptamer, miR-122, Pharmacosome, Synergistic anticancer effect, Tumor microenvironments",

author = "Fangqin Xue and Xiao Lin and Zhixiong Cai and Xiaolong Liu and Yuan Ma and Ming Wu",

note = "Funding Information: This work was supported by the Science and Technology General Program of Fujian Province (Grant No. 2018J01263), the Special Funds of Fujian Provincial Department of Finance (Grant Nos. (2020)500#, (2018)710#), the joint research projects of Health and Education Commission of Fujian Province (Grant No. 2019-WJ-20), the Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant No. 2019Y9046). Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

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doi = "10.1016/j.colsurfb.2020.111367",

language = "English",

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AU - Xue, Fangqin

AU - Lin, Xiao

AU - Cai, Zhixiong

AU - Liu, Xiaolong

AU - Ma, Yuan

AU - Wu, Ming

N1 - Funding Information: This work was supported by the Science and Technology General Program of Fujian Province (Grant No. 2018J01263), the Special Funds of Fujian Provincial Department of Finance (Grant Nos. (2020)500#, (2018)710#), the joint research projects of Health and Education Commission of Fujian Province (Grant No. 2019-WJ-20), the Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant No. 2019Y9046). Publisher Copyright: © 2020 Elsevier B.V.

PY - 2021/1

Y1 - 2021/1

N2 - A novel kind of anti-cancer pharmacosome (named NPC-D) derived from Doxifluridine (5′-DFUR) was described, which could be activated by tumor microenvironments (TMEs). The NPC-D with H2O2-sensitive linker was dispersed well in water and simultaneously interacted with nucleic acids including plasmids encoding miR-122 (p122) and EpCAM-targeted aptamer (ap1) via charge interaction and hydrogen bonding. The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of H2O2 and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment.

AB - A novel kind of anti-cancer pharmacosome (named NPC-D) derived from Doxifluridine (5′-DFUR) was described, which could be activated by tumor microenvironments (TMEs). The NPC-D with H2O2-sensitive linker was dispersed well in water and simultaneously interacted with nucleic acids including plasmids encoding miR-122 (p122) and EpCAM-targeted aptamer (ap1) via charge interaction and hydrogen bonding. The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of H2O2 and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment.

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KW - miR-122

KW - Pharmacosome

KW - Synergistic anticancer effect

KW - Tumor microenvironments

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Doxifluridine-based pharmacosomes delivering miR-122 as tumor microenvironments-activated nanoplatforms for synergistic treatment of hepatocellular carcinoma

Abstract

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