Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer

Lingyu Zhang,1,* Wenshu Chen,2,* Guihui Tu,1 Xingyong Chen,2 Youguang Lu,3 Lixian Wu,1 Dali Zheng3 1School of Pharmacy, Fujian Medical University, University Town, Fuzhou 350122, People’s Republic of China; 2Shengli Clinical College, Fujian Medical University, Fuzhou 350001, People&rsq...

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Autores principales:	Zhang L, Chen W, Tu G, Chen X, Lu Y, Wu L, Zheng D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	anticancer tea polyphenol nanoparticles nf-κb Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ef888df75848427bb36f8715450eca99
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spelling	oai:doaj.org-article:ef888df75848427bb36f8715450eca992021-12-02T09:34:43ZEnhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer1178-2013https://doaj.org/article/ef888df75848427bb36f8715450eca992020-06-01T00:00:00Zhttps://www.dovepress.com/enhanced-chemotherapeutic-efficacy-of-plga-encapsulated-epigallocatech-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lingyu Zhang,1,* Wenshu Chen,2,* Guihui Tu,1 Xingyong Chen,2 Youguang Lu,3 Lixian Wu,1 Dali Zheng3 1School of Pharmacy, Fujian Medical University, University Town, Fuzhou 350122, People’s Republic of China; 2Shengli Clinical College, Fujian Medical University, Fuzhou 350001, People’s Republic of China; 3Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dali ZhengKey Laboratory of Stomatology of Fujian Province, Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Road, Fuzhou 350004, People’s Republic of ChinaEmail dalizheng@fjmu.edu.cnLixian WuSchool of Pharmacy, Fujian Medical University, 1 Xueyuan Road, University Town, Fuzhou 350122, People’s Republic of ChinaEmail 18259000966@126.comPurpose: Currently, the clinical benefits of tea polyphenols have contributed to the development of efficient systemic delivery systems with adequate bioavailability and stability. In this study, we aimed to establish a nanoparticle model to overcome the shortcomings of epigallocatechin gallate (EGCG) in the treatment of lung cancer.Materials and Methods: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with EGCG were prepared by the oil-in-water emulsion solvent evaporation technique. The characteristics of NPs, entrapment efficiency, and in vitro release were systematically evaluated. The cellular uptake, cytotoxic activity, and the effect of the formulation on cellular apoptosis of free-from EGCG and the NPs were compared. The interaction between protein-NF-κB and EGCG was detected by bio-layer interferometry (BLI). NF-κB signaling was evaluated by Western blotting and q-RT-PCR. The efficacy of the optimized nanoformulation was evaluated using a patient-derived tumor xenograft (PDX) model.Results: EGCG-loaded NPs (175.8± 3.8 nm in size) demonstrated its optimal efficacy, with approximately 86.0% of encapsulation efficiency and 14.2% of loading efficiency. Additionally, EGCG-encapsulated PLGA-NPs offered a 3-4-fold dose advantage compared to free EGCG in terms of exerting antiproliferative effects and inducing apoptosis at lower doses (12.5, 25 μM). Molecular interaction assays demonstrated that EGCG binds to NF-κB with high affnity (KD=4.8× 10− 5 M). EGCG-NPs were more effective at inhibiting NF-κB activation and suppressing the expression of NF-κB-regulated genes than free EGCG. Furthermore, EGCG-NPs showed superior anticancer activity in the PDX model than free EGCG.Conclusion: These findings indicated that the prepared EGCG-NPs were more effective than free EGCG in inhibiting lung cancer tumors in the PDX model.Keywords: anticancer, tea polyphenol, nanoparticles, NF-κBZhang LChen WTu GChen XLu YWu LZheng DDove Medical Pressarticleanticancertea polyphenolnanoparticlesnf-κbMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4417-4429 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	anticancer tea polyphenol nanoparticles nf-κb Medicine (General) R5-920
spellingShingle	anticancer tea polyphenol nanoparticles nf-κb Medicine (General) R5-920 Zhang L Chen W Tu G Chen X Lu Y Wu L Zheng D Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer
description	Lingyu Zhang,1,* Wenshu Chen,2,* Guihui Tu,1 Xingyong Chen,2 Youguang Lu,3 Lixian Wu,1 Dali Zheng3 1School of Pharmacy, Fujian Medical University, University Town, Fuzhou 350122, People’s Republic of China; 2Shengli Clinical College, Fujian Medical University, Fuzhou 350001, People’s Republic of China; 3Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dali ZhengKey Laboratory of Stomatology of Fujian Province, Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Road, Fuzhou 350004, People’s Republic of ChinaEmail dalizheng@fjmu.edu.cnLixian WuSchool of Pharmacy, Fujian Medical University, 1 Xueyuan Road, University Town, Fuzhou 350122, People’s Republic of ChinaEmail 18259000966@126.comPurpose: Currently, the clinical benefits of tea polyphenols have contributed to the development of efficient systemic delivery systems with adequate bioavailability and stability. In this study, we aimed to establish a nanoparticle model to overcome the shortcomings of epigallocatechin gallate (EGCG) in the treatment of lung cancer.Materials and Methods: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with EGCG were prepared by the oil-in-water emulsion solvent evaporation technique. The characteristics of NPs, entrapment efficiency, and in vitro release were systematically evaluated. The cellular uptake, cytotoxic activity, and the effect of the formulation on cellular apoptosis of free-from EGCG and the NPs were compared. The interaction between protein-NF-κB and EGCG was detected by bio-layer interferometry (BLI). NF-κB signaling was evaluated by Western blotting and q-RT-PCR. The efficacy of the optimized nanoformulation was evaluated using a patient-derived tumor xenograft (PDX) model.Results: EGCG-loaded NPs (175.8± 3.8 nm in size) demonstrated its optimal efficacy, with approximately 86.0% of encapsulation efficiency and 14.2% of loading efficiency. Additionally, EGCG-encapsulated PLGA-NPs offered a 3-4-fold dose advantage compared to free EGCG in terms of exerting antiproliferative effects and inducing apoptosis at lower doses (12.5, 25 μM). Molecular interaction assays demonstrated that EGCG binds to NF-κB with high affnity (KD=4.8× 10− 5 M). EGCG-NPs were more effective at inhibiting NF-κB activation and suppressing the expression of NF-κB-regulated genes than free EGCG. Furthermore, EGCG-NPs showed superior anticancer activity in the PDX model than free EGCG.Conclusion: These findings indicated that the prepared EGCG-NPs were more effective than free EGCG in inhibiting lung cancer tumors in the PDX model.Keywords: anticancer, tea polyphenol, nanoparticles, NF-κB
format	article
author	Zhang L Chen W Tu G Chen X Lu Y Wu L Zheng D
author_facet	Zhang L Chen W Tu G Chen X Lu Y Wu L Zheng D
author_sort	Zhang L
title	Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer
title_short	Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer
title_full	Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer
title_fullStr	Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer
title_full_unstemmed	Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer
title_sort	enhanced chemotherapeutic efficacy of plga-encapsulated epigallocatechin gallate (egcg) against human lung cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/ef888df75848427bb36f8715450eca99
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Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer

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