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Nano Research 2019, 12(10): 2451-2459 https://doi.org/10.1007/s12274-019-2488-3
Research Article | Issue | Published: 03 August 2019

Novel fibronectin-targeted nanodisk drug delivery system displayed superior efficacy against prostate cancer compared with nanospheres

Show Author's Information Luyao Wang,  Bingjie Zhou,  Shiqi Huang,  Mengke Qu,  Qing Lin,  Tao Gong,  Yuan Huang,  Xun Sun,  Qin He,  Zhirong Zhang,  Ling Zhang( )
Key Laboratory of Drug Targeting and Drug Delivery Systems,Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University,Chengdu,610041,China;
Keywords:
prostate cancer, Cys-Arg-Glu-Lys-Ala peptide with N-methylated Glu (CR(NMe)EKA), fibronectin, nanodisks, tumor-targeting
Topics:
Chemotherapy Controlled drug deliveryDiseasesMedical applicationsNanoparticlesNanospheres SpheresTumorsUrology
Cite this article:
Wang L, Zhou B, Huang S, et al. Novel fibronectin-targeted nanodisk drug delivery system displayed superior efficacy against prostate cancer compared with nanospheres. Nano Research, 2019, 12(10): 2451-2459. https://doi.org/10.1007/s12274-019-2488-3
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Abstract Full text Electronic supplementary material About this article

Currently, prostate cancer is the most frequently diagnosed cancer in males and chemotherapy is often essential for treating advanced prostate cancer. However, common chemotherapies for prostate cancer suffer from serious adverse effects due to poor drug targeting ability and tissue penetration, even with the help of conventional drug delivery systems. Here, encouraged by recent studies showing possible drug retention and tissue penetration advantages of unconventional non-spherical nanoparticles over conventional spherical nanoparticles, we design and construct a novel non-spherical nanodisk drug delivery system for treating prostate cancer. In order to enhance tumor-targeting capability, these nanodisks are further modified with targeting peptide, Cys-Arg-Glu-Lys-Ala peptide with N-methylated Glu (CR(NMe)EKA), which recognizes extracellular matrix fibronectin and its complexes specifically expressed on the walls of tumor vessels and in tumor stroma. Compared with conventional nanospheres, the nanodisks achieve much higher drug accumulation at prostate tumor sites. When loaded with paclitaxel, the CR(NMe)EKA-modified nanodisks display superior antitumor efficacy to free paclitaxel, unmodified nanodisks and nanospheres. In summary, our study provides an attractive therapeutic strategy for targeted therapy against prostate cancer with simple preparation, high efficiency and low toxicity, and supplements a theoretical support for treatments realized by different shaped nanoplatforms. Our study also offers valuable data for understanding biological effects of non-spherical nanodisks and highlights the great potential of unconventional nanoparticles in biomedical applications.


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Electronic supplementary material
About this article

Novel fibronectin-targeted nanodisk drug delivery system displayed superior efficacy against prostate cancer compared with nanospheres

Show Author's information Luyao Wang, Bingjie Zhou, Shiqi Huang, Mengke Qu, Qing Lin, Tao Gong, Yuan Huang, Xun Sun, Qin He, Zhirong Zhang, Ling Zhang( )
Key Laboratory of Drug Targeting and Drug Delivery Systems,Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University,Chengdu,610041,China;

Abstract

Currently, prostate cancer is the most frequently diagnosed cancer in males and chemotherapy is often essential for treating advanced prostate cancer. However, common chemotherapies for prostate cancer suffer from serious adverse effects due to poor drug targeting ability and tissue penetration, even with the help of conventional drug delivery systems. Here, encouraged by recent studies showing possible drug retention and tissue penetration advantages of unconventional non-spherical nanoparticles over conventional spherical nanoparticles, we design and construct a novel non-spherical nanodisk drug delivery system for treating prostate cancer. In order to enhance tumor-targeting capability, these nanodisks are further modified with targeting peptide, Cys-Arg-Glu-Lys-Ala peptide with N-methylated Glu (CR(NMe)EKA), which recognizes extracellular matrix fibronectin and its complexes specifically expressed on the walls of tumor vessels and in tumor stroma. Compared with conventional nanospheres, the nanodisks achieve much higher drug accumulation at prostate tumor sites. When loaded with paclitaxel, the CR(NMe)EKA-modified nanodisks display superior antitumor efficacy to free paclitaxel, unmodified nanodisks and nanospheres. In summary, our study provides an attractive therapeutic strategy for targeted therapy against prostate cancer with simple preparation, high efficiency and low toxicity, and supplements a theoretical support for treatments realized by different shaped nanoplatforms. Our study also offers valuable data for understanding biological effects of non-spherical nanodisks and highlights the great potential of unconventional nanoparticles in biomedical applications.

Keywords: prostate cancer, Cys-Arg-Glu-Lys-Ala peptide with N-methylated Glu (CR(NMe)EKA), fibronectin, nanodisks, tumor-targeting

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Publication history
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Acknowledgements

Publication history

Received: 25 May 2019
Revised: 11 July 2019
Accepted: 20 July 2019
Published: 03 August 2019
Issue date: October 2019

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81690261 and 81872824).

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