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A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma
Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for an...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515951/ https://www.ncbi.nlm.nih.gov/pubmed/36185205 http://dx.doi.org/10.3389/fonc.2022.932156 |
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author | Xie, Ming-Hua Fu, Zai-Lin Hua, Ai-Lian Zhou, Ji-Fang Chen, Qian Li, Jian-Bo Yao, Shen Cai, Xin-Jun Ge, Min Zhou, Li Wu, Jia |
author_facet | Xie, Ming-Hua Fu, Zai-Lin Hua, Ai-Lian Zhou, Ji-Fang Chen, Qian Li, Jian-Bo Yao, Shen Cai, Xin-Jun Ge, Min Zhou, Li Wu, Jia |
author_sort | Xie, Ming-Hua |
collection | PubMed |
description | Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs. |
format | Online Article Text |
id | pubmed-9515951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95159512022-09-29 A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma Xie, Ming-Hua Fu, Zai-Lin Hua, Ai-Lian Zhou, Ji-Fang Chen, Qian Li, Jian-Bo Yao, Shen Cai, Xin-Jun Ge, Min Zhou, Li Wu, Jia Front Oncol Oncology Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9515951/ /pubmed/36185205 http://dx.doi.org/10.3389/fonc.2022.932156 Text en Copyright © 2022 Xie, Fu, Hua, Zhou, Chen, Li, Yao, Cai, Ge, Zhou and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Xie, Ming-Hua Fu, Zai-Lin Hua, Ai-Lian Zhou, Ji-Fang Chen, Qian Li, Jian-Bo Yao, Shen Cai, Xin-Jun Ge, Min Zhou, Li Wu, Jia A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma |
title | A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma |
title_full | A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma |
title_fullStr | A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma |
title_full_unstemmed | A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma |
title_short | A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma |
title_sort | new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with aprpg enhances anti-tumor effects in hepatocellular carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515951/ https://www.ncbi.nlm.nih.gov/pubmed/36185205 http://dx.doi.org/10.3389/fonc.2022.932156 |
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