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Stearic Acid-Grafted Chitooligosaccharide Nanomicelle System with Biocleavable Gadolinium Chelates as a Multifunctional Agent for Tumor Imaging and Drug Delivery

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Abstract

Purpose

Theranostic nanoplatforms are promising approaches for diagnosis and treatment. Here, we report a drug-loaded nanomicelle system with biocleavable gadolinium (Gd) chelates as a multifunctional biodegradable agent for simultaneous magnetic resonance imaging (MRI) and drug delivery.

Methods

Self-assembled nanomicelles based on stearic acid-grafted chitooligosaccharide were utilized as vehicles. Gd chelates, DTPA-Gds, were linked to the nanomicelles via redox-responsive disulfide bonds, and hydrophobic drugs were encapsulated in the micelle cores. MRI and cargo delivery were investigated in orthotopic pancreatic tumor-bearing mice.

Results

In vivo MRI demonstrated that the biodegradable agent was cleaved by endogenous thiols after intravenous injection, and the released DTPA-Gds were eliminated rapidly. At the same time, the agent resulted in a greater contrast enhancement of T1-weighted MR signal intensity at the tumor region than Magnevist®, and the tumor boundaries were clearly defined for at least 2 h. In addition, the agent possessed high drug-loading and tumor-targeting capacities. Loading content and encapsulation efficiency of docetaxel were 3.2% and 99.4%, respectively. Compared with Taxotere®, the commercially available docetaxel injection, the docetaxel-loaded agent significantly increased the drug concentration in tumor tissue in vivo.

Conclusion

The fabricated multifunctional agent may serve as a biodegradable nanoscale MRI contrast agent and as a drug delivery system for tumor diagnosis and treatment.

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Abbreviations

BisPDSEA-DTPA-Gd:

Bis(2-pyridin-2-yldisulfanyl ethylamido)diethylenetriaminepentaacetic acid gadolinium complex

CAs:

Contrast agents

COS:

Chitooligosaccharide

COSSA:

Stearic acid-grafted chitooligosaccharide

COS-NAC:

N-acetylcysteine-grafted COS

DTX:

Docetaxel

MBA:

Multifunctional biodegradable agent

MNGCs:

Macromolecular and nanoscale Gd complexes

NAC:

N-acetylcysteine

PDSEA•HCl:

2-(pyridin-2-yldisulfanyl)ethanamine hydrochloride

SA:

Stearic acid

-ss- :

Disulfide bonds

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Acknowledgments and Disclosures

TThis work was supported by the Shanghai Natural Science Foundation (16ZR1405900). The authors thank the staff of the Center of Analysis & Test at East China University of Science and Technology for helping with the ICP-OES measurement.

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China

    Chuhua Xin, Bin Du, Weiyu Yang, Liuguo Wang, Lirong Ma & Weiyu Weng

  2. Department of Radiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China

    Xiuzhong Yao

  3. Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, People’s Republic of China

    Weiyu Weng

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  1. Chuhua Xin
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  2. Xiuzhong Yao
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Correspondence to Weiyu Weng.

Additional information

Chuhua Xin and Xiuzhong Yao contributed equally to this work.

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Xin, C., Yao, X., Du, B. et al. Stearic Acid-Grafted Chitooligosaccharide Nanomicelle System with Biocleavable Gadolinium Chelates as a Multifunctional Agent for Tumor Imaging and Drug Delivery. Pharm Res 36, 10 (2019). https://doi.org/10.1007/s11095-018-2530-2

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  • DOI: https://doi.org/10.1007/s11095-018-2530-2

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