Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy

Yuzhu Hu, 1–3 Yihong He, 1–3 Jianrui Ji, 1 Songping Zheng, 1–3 Yongzhong Cheng 1–3 1Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University and Collaborat...

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Main Authors: Hu Y, He Y, Ji J, Zheng S, Cheng Y
Format: Article
Language:English
Published: Dove Medical Press 2020-02-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/tumor-targeted-curcumin-delivery-by-folate-modified-mpeg-pcl-self-asse-peer-reviewed-article-IJN
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author Hu Y
He Y
Ji J
Zheng S
Cheng Y
author_facet Hu Y
He Y
Ji J
Zheng S
Cheng Y
author_sort Hu Y
collection DOAJ
description Yuzhu Hu, 1–3 Yihong He, 1–3 Jianrui Ji, 1 Songping Zheng, 1–3 Yongzhong Cheng 1–3 1Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, People’s Republic of China; 2Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China; 3Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Songping Zheng; Yongzhong ChengDepartment of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of ChinaTel +86 28 8516 4063Email 13618088051@163.com; chengyz@scu.edu.cnIntroduction: Curcumin (Cur) is a natural extract of Asian spice Curcumin longa, showing multi-targeting capability and low toxicity in anti-tumor activities. The low bioavailability restricts its application as a therapeutic agent. Folate (FA) receptors are highly expressed in many malignant tumors while low expressed in normal tissue. Herein, we developed a self-assembled FA modified MPEG-PCL micelle to incorporate Cur (FA/Nano-Cur) and applied it for colorectal cancer therapy.Methods: We prepared FA/Nano-Cur micelles and identified their characteristics. The drug release behavior, pharmacokinetics and in vitro anti-tumor activities of FA/Nano-Cur were studied. Furthermore, the in vivo anti-tumor ability assessment and anti-tumor mechanisms investigation were carried out in murine colorectal cancer model.Results: FA/Nano-Cur micelles had an average particle size of 30.47 nm. Elongated T 1/2 and larger AUC were found in FA/Nano-Cur group than that in the Free Cur group. MTT assay and apoptotic study indicated the growth inhibitory effect and pro-apoptotic effect of FA/Nano-Cur were the most significant among all treatments. Moreover, the in vivo study demonstrated that FA/Nano-Cur micelles exhibited a much stronger effect to suppress tumor growth, promote tumor apoptosis and attenuate tumor angiogenesis than Free Cur and Nano-Cur micelles.Conclusion: The present study demonstrated FA/Nano-Cur micelles might be a promising therapeutic agent in colorectal cancer treatment with distinctive advantages of improved bioavailability, sustained drug release, tumor-targeted delivery and low toxicity.Keywords: curcumin, colorectal cancer, folate, nanoformulation, apoptosis, angiogenesis
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spelling doaj.art-ddb58ac705fa4b56b2143005a65f833a2022-12-21T19:27:31ZengDove Medical PressInternational Journal of Nanomedicine1178-20132020-02-01Volume 151239125252002Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer TherapyHu YHe YJi JZheng SCheng YYuzhu Hu, 1–3 Yihong He, 1–3 Jianrui Ji, 1 Songping Zheng, 1–3 Yongzhong Cheng 1–3 1Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, People’s Republic of China; 2Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China; 3Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Songping Zheng; Yongzhong ChengDepartment of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of ChinaTel +86 28 8516 4063Email 13618088051@163.com; chengyz@scu.edu.cnIntroduction: Curcumin (Cur) is a natural extract of Asian spice Curcumin longa, showing multi-targeting capability and low toxicity in anti-tumor activities. The low bioavailability restricts its application as a therapeutic agent. Folate (FA) receptors are highly expressed in many malignant tumors while low expressed in normal tissue. Herein, we developed a self-assembled FA modified MPEG-PCL micelle to incorporate Cur (FA/Nano-Cur) and applied it for colorectal cancer therapy.Methods: We prepared FA/Nano-Cur micelles and identified their characteristics. The drug release behavior, pharmacokinetics and in vitro anti-tumor activities of FA/Nano-Cur were studied. Furthermore, the in vivo anti-tumor ability assessment and anti-tumor mechanisms investigation were carried out in murine colorectal cancer model.Results: FA/Nano-Cur micelles had an average particle size of 30.47 nm. Elongated T 1/2 and larger AUC were found in FA/Nano-Cur group than that in the Free Cur group. MTT assay and apoptotic study indicated the growth inhibitory effect and pro-apoptotic effect of FA/Nano-Cur were the most significant among all treatments. Moreover, the in vivo study demonstrated that FA/Nano-Cur micelles exhibited a much stronger effect to suppress tumor growth, promote tumor apoptosis and attenuate tumor angiogenesis than Free Cur and Nano-Cur micelles.Conclusion: The present study demonstrated FA/Nano-Cur micelles might be a promising therapeutic agent in colorectal cancer treatment with distinctive advantages of improved bioavailability, sustained drug release, tumor-targeted delivery and low toxicity.Keywords: curcumin, colorectal cancer, folate, nanoformulation, apoptosis, angiogenesishttps://www.dovepress.com/tumor-targeted-curcumin-delivery-by-folate-modified-mpeg-pcl-self-asse-peer-reviewed-article-IJNcurcumincolorectal cancerfolatenanoformulationapoptosisangiogenesis
spellingShingle Hu Y
He Y
Ji J
Zheng S
Cheng Y
Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy
International Journal of Nanomedicine
curcumin
colorectal cancer
folate
nanoformulation
apoptosis
angiogenesis
title Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy
title_full Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy
title_fullStr Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy
title_full_unstemmed Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy
title_short Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy
title_sort tumor targeted curcumin delivery by folate modified mpeg pcl self assembly micelles for colorectal cancer therapy
topic curcumin
colorectal cancer
folate
nanoformulation
apoptosis
angiogenesis
url https://www.dovepress.com/tumor-targeted-curcumin-delivery-by-folate-modified-mpeg-pcl-self-asse-peer-reviewed-article-IJN
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