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A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism

In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparti...

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Autores principales: Liu, Hui, Guo, Chunlei, Shang, Yuhong, Zeng, Lin, Jia, Haixue, Wang, Zhongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724251/
https://www.ncbi.nlm.nih.gov/pubmed/34993192
http://dx.doi.org/10.3389/fbioe.2021.804747
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author Liu, Hui
Guo, Chunlei
Shang, Yuhong
Zeng, Lin
Jia, Haixue
Wang, Zhongyan
author_facet Liu, Hui
Guo, Chunlei
Shang, Yuhong
Zeng, Lin
Jia, Haixue
Wang, Zhongyan
author_sort Liu, Hui
collection PubMed
description In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparticles mainly composed of an anticancer drug of PEM (PEM-FFRGD) were prepared to deliver PEM to tumors. The peptide could self-assemble into a nanoparticle structure with diameter of about 20 nm. Moreover, the nanoparticle showed favorable solubility and biocompatibility compared with those of PEM, and the MTT test on A549 and LLC cells showed that the PEM-FFRGD nanoparticles had stronger cytotoxic activity than PEM alone. Most importantly, the nanoparticle could promote tumor apoptosis and decrease mitochondrial energy metabolism in tumors. In vivo studies indicated that PEM-FFRGD nanoparticles had enhanced antitumor efficacy in LLC tumor-bearing mice compared to that of PEM. Our observations suggested that PEM-FFRGD nanoparticles have great practical potential for application in lung cancer therapy.
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spelling pubmed-87242512022-01-05 A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism Liu, Hui Guo, Chunlei Shang, Yuhong Zeng, Lin Jia, Haixue Wang, Zhongyan Front Bioeng Biotechnol Bioengineering and Biotechnology In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparticles mainly composed of an anticancer drug of PEM (PEM-FFRGD) were prepared to deliver PEM to tumors. The peptide could self-assemble into a nanoparticle structure with diameter of about 20 nm. Moreover, the nanoparticle showed favorable solubility and biocompatibility compared with those of PEM, and the MTT test on A549 and LLC cells showed that the PEM-FFRGD nanoparticles had stronger cytotoxic activity than PEM alone. Most importantly, the nanoparticle could promote tumor apoptosis and decrease mitochondrial energy metabolism in tumors. In vivo studies indicated that PEM-FFRGD nanoparticles had enhanced antitumor efficacy in LLC tumor-bearing mice compared to that of PEM. Our observations suggested that PEM-FFRGD nanoparticles have great practical potential for application in lung cancer therapy. Frontiers Media S.A. 2021-12-21 /pmc/articles/PMC8724251/ /pubmed/34993192 http://dx.doi.org/10.3389/fbioe.2021.804747 Text en Copyright © 2021 Liu, Guo, Shang, Zeng, Jia and Wang. 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 Bioengineering and Biotechnology
Liu, Hui
Guo, Chunlei
Shang, Yuhong
Zeng, Lin
Jia, Haixue
Wang, Zhongyan
A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism
title A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism
title_full A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism
title_fullStr A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism
title_full_unstemmed A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism
title_short A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism
title_sort supramolecular nanoparticle of pemetrexed improves the anti-tumor effect by inhibiting mitochondrial energy metabolism
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724251/
https://www.ncbi.nlm.nih.gov/pubmed/34993192
http://dx.doi.org/10.3389/fbioe.2021.804747
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