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Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery
BACKGROUND: The clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650835/ https://www.ncbi.nlm.nih.gov/pubmed/34887660 http://dx.doi.org/10.2147/IJN.S331060 |
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author | Xu, Bing Yan, Mengmeng Zhou, Fei Cai, Desheng Guo, Wenbo Jia, Xiaohui Liu, Runping Ma, Tao Li, Tong Gao, Feng Wang, Penglong Lei, Haimin |
author_facet | Xu, Bing Yan, Mengmeng Zhou, Fei Cai, Desheng Guo, Wenbo Jia, Xiaohui Liu, Runping Ma, Tao Li, Tong Gao, Feng Wang, Penglong Lei, Haimin |
author_sort | Xu, Bing |
collection | PubMed |
description | BACKGROUND: The clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT-WT-H NPs) for highly efficient CPT delivery and effective cancer therapy. METHODS AND RESULTS: In this study, smart self-assembled nanoparticles CPT-WT-H NPs were elaborately designed and synthesized by combing hydrophobic CPT with hydrophilic PSMA-responsive penta-peptide via a cleavable ester bond. This dual responsive nanoparticle with negatively charged surface first respond to the extracellular PSMA and then to the intracellular esterase, achieving a programmable release of CPT at the tumor site and producing the byproducts of biocompatible glutamic acid and aspartic acid. Our data demonstrated that CPT-WT-H NPs exhibited greatly improved water solubility and stability. Results from MTT and flow cytometry showed CPT-WT-H NPs exhibited significantly higher cytotoxicity as well as apoptosis-inducing activity against PSMA-expressing LNCaP-FGC cells than the non-PSMA-expressing cancer cells, showing excellent cytotoxic selectivity. Moreover, the unique nanostructure provided the efficient transportation of CPT to tumor site, which resulted in the effective inhibition of tumor growth and low systemic toxicity in vivo. CONCLUSION: CPT-WT-H NPs exhibited excellent in vitro PSMA-response ability and in vivo antitumor activity and safety, holding the promise to become a new and potent anticancer drug. The current research presents a promising strategy for efficient drug delivery. |
format | Online Article Text |
id | pubmed-8650835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-86508352021-12-08 Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery Xu, Bing Yan, Mengmeng Zhou, Fei Cai, Desheng Guo, Wenbo Jia, Xiaohui Liu, Runping Ma, Tao Li, Tong Gao, Feng Wang, Penglong Lei, Haimin Int J Nanomedicine Original Research BACKGROUND: The clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT-WT-H NPs) for highly efficient CPT delivery and effective cancer therapy. METHODS AND RESULTS: In this study, smart self-assembled nanoparticles CPT-WT-H NPs were elaborately designed and synthesized by combing hydrophobic CPT with hydrophilic PSMA-responsive penta-peptide via a cleavable ester bond. This dual responsive nanoparticle with negatively charged surface first respond to the extracellular PSMA and then to the intracellular esterase, achieving a programmable release of CPT at the tumor site and producing the byproducts of biocompatible glutamic acid and aspartic acid. Our data demonstrated that CPT-WT-H NPs exhibited greatly improved water solubility and stability. Results from MTT and flow cytometry showed CPT-WT-H NPs exhibited significantly higher cytotoxicity as well as apoptosis-inducing activity against PSMA-expressing LNCaP-FGC cells than the non-PSMA-expressing cancer cells, showing excellent cytotoxic selectivity. Moreover, the unique nanostructure provided the efficient transportation of CPT to tumor site, which resulted in the effective inhibition of tumor growth and low systemic toxicity in vivo. CONCLUSION: CPT-WT-H NPs exhibited excellent in vitro PSMA-response ability and in vivo antitumor activity and safety, holding the promise to become a new and potent anticancer drug. The current research presents a promising strategy for efficient drug delivery. Dove 2021-12-03 /pmc/articles/PMC8650835/ /pubmed/34887660 http://dx.doi.org/10.2147/IJN.S331060 Text en © 2021 Xu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Xu, Bing Yan, Mengmeng Zhou, Fei Cai, Desheng Guo, Wenbo Jia, Xiaohui Liu, Runping Ma, Tao Li, Tong Gao, Feng Wang, Penglong Lei, Haimin Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery |
title | Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery |
title_full | Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery |
title_fullStr | Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery |
title_full_unstemmed | Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery |
title_short | Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin–Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery |
title_sort | prostate-specific membrane antigen and esterase dual responsive camptothecin–oligopeptide self-assembled nanoparticles for efficient anticancer drug delivery |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650835/ https://www.ncbi.nlm.nih.gov/pubmed/34887660 http://dx.doi.org/10.2147/IJN.S331060 |
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