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

Authors Hu Y, He Y, Ji J, Zheng S, Cheng Y

Received 28 September 2019

Accepted for publication 2 January 2020

Published 21 February 2020 Volume 2020:15 Pages 1239—1252

DOI https://doi.org/10.2147/IJN.S232777

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Mian Wang


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 China

Correspondence: Songping Zheng; Yongzhong Cheng
Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China
Tel +86 28 8516 4063
Email 13618088051@163.com; chengyz@scu.edu.cn

Introduction: 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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