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Nano Research

Article Title

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

Authors

Luyao Wang, 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
Bingjie Zhou, 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
Shiqi Huang, 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
Mengke Qu, 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
Qing Lin, 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
Tao Gong, 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
Yuan Huang, 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
Xun Sun, 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
Qin He, 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
Zhirong 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
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

CR(NMe)EKA, fibronectin, nanodisks, prostate cancer, tumor-targeting

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 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.

Graphical Abstract

Publisher

Tsinghua University Press

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