Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer

Pingping Wu,1,2 Huayun Zhu,2 Yan Zhuang,2 Xiaofeng Sun,2 Ning Gu1 1State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of China; 2Departme...

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Autores principales:	Wu P, Zhu H, Zhuang Y, Sun X, Gu N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	peg-pla 5fu 131i drug delivery radio-chemotherapy colorectal cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4c689043ee8045dea4621523e448eafe
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spelling	oai:doaj.org-article:4c689043ee8045dea4621523e448eafe2021-12-02T09:58:40ZCombined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer1178-2013https://doaj.org/article/4c689043ee8045dea4621523e448eafe2020-04-01T00:00:00Zhttps://www.dovepress.com/combined-therapeutic-effects-of-131i-labeled-and-5fu-loaded-multifunct-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Pingping Wu,1,2 Huayun Zhu,2 Yan Zhuang,2 Xiaofeng Sun,2 Ning Gu1 1State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of China; 2Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Ning GuState Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of ChinaTel +86 130 7253 2619Email guning@seu.edu.cnBackground: Owing to its combined effects, the co-delivery of different therapeutics is a promising option for the treatment of cancer. In the present study, tumor-targeting poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles were developed for the transportation of two molecules, namely chemotherapeutic drug 5-fluorouracil (5Fu) and radionuclide iodine-131 (131I), in a single platform.Methods: The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-131I) were spherical (diameter approximately 110 nm) and pH-sensitive. The targeting effect of nanoparticles via Cet was confirmed in colorectal cancer cells using a fluorescent assay. The combined effects of Cet-PEG-PLA-5Fu-131I on cell viability and apoptosis were evaluated in colorectal cancer cells by Cell Counting Kit-8 and flow cytometry assays.Results: Blank nanoparticles (Cet-PEG-PLA) showed good biocompatibility, and Cet-PEG-PLA-5Fu-131I nanoparticles were the most effective in terms of inhibition of cell viability and induction of apoptosis compared with monotherapy using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I alone, Cet-PEG-PLA-5Fu-131I nanoparticles exhibited prolonged circulation in the blood and accumulation in the tumor, thus resulting in enhanced antitumor efficacy. Additionally, combined radio-chemotherapy with Cet-PEG-PLA-5Fu-131I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-131I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses.Conclusion: The multifunctional Cet-PEG-PLA-5Fu-131I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and 131I-mediated radiotherapy.Keywords: PEG-PLA, 5Fu, 131I, drug delivery, radio-chemotherapy, colorectal cancerWu PZhu HZhuang YSun XGu NDove Medical Pressarticlepeg-pla5fu131idrug deliveryradio-chemotherapycolorectal cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2777-2787 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	peg-pla 5fu 131i drug delivery radio-chemotherapy colorectal cancer Medicine (General) R5-920
spellingShingle	peg-pla 5fu 131i drug delivery radio-chemotherapy colorectal cancer Medicine (General) R5-920 Wu P Zhu H Zhuang Y Sun X Gu N Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer
description	Pingping Wu,1,2 Huayun Zhu,2 Yan Zhuang,2 Xiaofeng Sun,2 Ning Gu1 1State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of China; 2Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Ning GuState Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of ChinaTel +86 130 7253 2619Email guning@seu.edu.cnBackground: Owing to its combined effects, the co-delivery of different therapeutics is a promising option for the treatment of cancer. In the present study, tumor-targeting poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles were developed for the transportation of two molecules, namely chemotherapeutic drug 5-fluorouracil (5Fu) and radionuclide iodine-131 (131I), in a single platform.Methods: The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-131I) were spherical (diameter approximately 110 nm) and pH-sensitive. The targeting effect of nanoparticles via Cet was confirmed in colorectal cancer cells using a fluorescent assay. The combined effects of Cet-PEG-PLA-5Fu-131I on cell viability and apoptosis were evaluated in colorectal cancer cells by Cell Counting Kit-8 and flow cytometry assays.Results: Blank nanoparticles (Cet-PEG-PLA) showed good biocompatibility, and Cet-PEG-PLA-5Fu-131I nanoparticles were the most effective in terms of inhibition of cell viability and induction of apoptosis compared with monotherapy using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I alone, Cet-PEG-PLA-5Fu-131I nanoparticles exhibited prolonged circulation in the blood and accumulation in the tumor, thus resulting in enhanced antitumor efficacy. Additionally, combined radio-chemotherapy with Cet-PEG-PLA-5Fu-131I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-131I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses.Conclusion: The multifunctional Cet-PEG-PLA-5Fu-131I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and 131I-mediated radiotherapy.Keywords: PEG-PLA, 5Fu, 131I, drug delivery, radio-chemotherapy, colorectal cancer
format	article
author	Wu P Zhu H Zhuang Y Sun X Gu N
author_facet	Wu P Zhu H Zhuang Y Sun X Gu N
author_sort	Wu P
title	Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer
title_short	Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer
title_full	Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer
title_fullStr	Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer
title_full_unstemmed	Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer
title_sort	combined therapeutic effects of 131i-labeled and 5fu-loaded multifunctional nanoparticles in colorectal cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/4c689043ee8045dea4621523e448eafe
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Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer

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