Cargando…

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

PURPOSE: 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 (EGC...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Lingyu, Chen, Wenshu, Tu, Guihui, Chen, Xingyong, Lu, Youguang, Wu, Lixian, Zheng, Dali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310995/
https://www.ncbi.nlm.nih.gov/pubmed/32606686
http://dx.doi.org/10.2147/IJN.S243657
_version_ 1783549473553645568
author Zhang, Lingyu
Chen, Wenshu
Tu, Guihui
Chen, Xingyong
Lu, Youguang
Wu, Lixian
Zheng, Dali
author_facet Zhang, Lingyu
Chen, Wenshu
Tu, Guihui
Chen, Xingyong
Lu, Youguang
Wu, Lixian
Zheng, Dali
author_sort Zhang, Lingyu
collection PubMed
description PURPOSE: 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.
format Online
Article
Text
id pubmed-7310995
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-73109952020-06-29 Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer Zhang, Lingyu Chen, Wenshu Tu, Guihui Chen, Xingyong Lu, Youguang Wu, Lixian Zheng, Dali Int J Nanomedicine Original Research PURPOSE: 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. Dove 2020-06-19 /pmc/articles/PMC7310995/ /pubmed/32606686 http://dx.doi.org/10.2147/IJN.S243657 Text en © 2020 Zhang et al. http://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/). 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
Zhang, Lingyu
Chen, Wenshu
Tu, Guihui
Chen, Xingyong
Lu, Youguang
Wu, Lixian
Zheng, Dali
Enhanced Chemotherapeutic Efficacy of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) Against Human Lung Cancer
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310995/
https://www.ncbi.nlm.nih.gov/pubmed/32606686
http://dx.doi.org/10.2147/IJN.S243657
work_keys_str_mv AT zhanglingyu enhancedchemotherapeuticefficacyofplgaencapsulatedepigallocatechingallateegcgagainsthumanlungcancer
AT chenwenshu enhancedchemotherapeuticefficacyofplgaencapsulatedepigallocatechingallateegcgagainsthumanlungcancer
AT tuguihui enhancedchemotherapeuticefficacyofplgaencapsulatedepigallocatechingallateegcgagainsthumanlungcancer
AT chenxingyong enhancedchemotherapeuticefficacyofplgaencapsulatedepigallocatechingallateegcgagainsthumanlungcancer
AT luyouguang enhancedchemotherapeuticefficacyofplgaencapsulatedepigallocatechingallateegcgagainsthumanlungcancer
AT wulixian enhancedchemotherapeuticefficacyofplgaencapsulatedepigallocatechingallateegcgagainsthumanlungcancer
AT zhengdali enhancedchemotherapeuticefficacyofplgaencapsulatedepigallocatechingallateegcgagainsthumanlungcancer