Citation: Zean Li, Jun Huang, Tao Du, Yiming Lai, Kaiwen Li, Man-Li Luo, Dingjun Zhu, Jun Wu, Hai Huang. Targeting the Rac1 pathway for improved prostate cancer therapy using polymeric nanoparticles to deliver of NSC23766[J]. Chinese Chemical Letters, ;2022, 33(5): 2496-2500. doi: 10.1016/j.cclet.2021.11.078 shu

Targeting the Rac1 pathway for improved prostate cancer therapy using polymeric nanoparticles to deliver of NSC23766

Zean Li ^{a, c, d, 1} ,
Jun Huang ^{b, 1} ,
Tao Du ^{e, 1} ,
Yiming Lai ^{a, c} ,
Kaiwen Li ^{a, c} ,
Man-Li Luo ^{c, d} ,
Dingjun Zhu ^{a, c, d, *,} ,
Jun Wu ^{b, **,} ,
Hai Huang ^{a, c, d, f, *,}

a.
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510220, China
b.
School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, China
c.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
d.
Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
e.
Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
f.
Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China

zhudingjun@163.com

wujun29@mail.sysu.edu.cn

huangh9@mail.sysu.edu.cn

Received Date: 14 September 2021
Revised Date: 23 November 2021
Accepted Date: 26 November 2021
Available Online: 2 December 2021

Figures(4)

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. The Rac1-GTP inhibitor NSC23766 has been shown to suppress PCa growth. However, these therapies have low tumor-targeting efficacy in vivo. Therefore, it is essential to produce a drug delivery system that specifically targets the tumor site. Herein, novel l-phenylalanine-based poly(ester amide) (Phe-PEA) polymers were synthesized and loaded with NSC23766 (NSC23766@8P6 NPs), which had a small particle size (162.3 ± 6.7 nm) and high NSC23766 loading (8.0% ± 1.1%) with a more rapid release of NSC23766 at pH 5.0. In vitro cellular uptake and cytotoxicity assays demonstrated that NSC23766@8P6 NPs were rapidly taken up by PC3 cells and showed significant effects of PCa cell proliferation inhibition and G2/M phase arrest. Furthermore, in vivo studies using PC3-bearing mice demonstrated that NSC23766@8P6 NPs delivered by intravenous injection not only increased the drug concentration with prolonged retention (96 h) at the tumor site, but also inhibited tumor growth and induced apoptosis. In conclusion, we have discovered that NSC23766@8P6 NPs can serve as a delivery system that targets the tumor site and is therefore a promising therapeutic approach for PCa treatment.
- Prostate cancer,
- NSC23766,
- Rac1,
- Nanoparticle,
- Poly(ester amide)
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