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)
1. [1]
  F. Bray, J. Ferlay, I. Soerjomataram, et al., CA Cancer J. Clin. 68 (2018) 394-424. doi: 10.3322/caac.21492
2. [2]
  G. Attard, C. Parker, R.A. Eeles, et al., Lancet 387 (2016) 70-82. doi: 10.1016/S0140-6736(14)61947-4
3. [3]
  M.S. Litwin, H.J. Tan, JAMA 317 (2017) 2532-2542. doi: 10.1001/jama.2017.7248
4. [4]
  T.A. Yap, A.D. Smith, R. Ferraldeschi, et al., Nat. Rev. Drug Discov. 15 (2016) 699-718. doi: 10.1038/nrd.2016.120
5. [5]
  P. Gu, X. Chen, R. Xie, et al., Mol. Cancer 18 (2019) 1-14. doi: 10.1186/s12943-018-0930-x
6. [6]
  S.M. Kim, T.T. Nguyen, A. Ravi, et al., Cancer Discov. 8 (2018) 866-883. doi: 10.1158/2159-8290.CD-17-1215
7. [7]
  M. Levay, K.A. Krobert, K. Wittig, et al., J. Pharmacol. Exp. Ther. 347 (2013) 69-79. doi: 10.1124/jpet.113.207266
8. [8]
  Z. Li, Q. Wang, S. Peng, et al., Clin. Transl. Med. 10 (2020) e191.
9. [9]
  J. Zhang, L. Wang, X. You, et al., Curr. Top. Med. Chem. 19 (2019) 57-73. doi: 10.2174/1568026619666190125145836
10. [10]
  C. Zheng, M. Li, J. Ding, BIO. Integr. 2 (2021) 57-60. doi: 10.15212/bioi-2021-0016
11. [11]
  X. Zhang, Z. Li, P. Yang, et al., Mater. Horiz. 8 (2021) 145-167. doi: 10.1039/D0MH01317J
12. [12]
  P. Yang, F. Zhu, Z. Zhang, et al., Chem. Soc. Rev. 50 (2021) 8319-8343. doi: 10.1039/D1CS00374G
13. [13]
  J. Hu, L. Yang, P. Yang, et al., Biomater. Sci. 8 (2020) 4940-4950. doi: 10.1039/D0BM01070G
14. [14]
  P. Zheng, Y. Liu, J. Chen, et al., Chin. Chem. Lett. 31 (2020) 1178-1182. doi: 10.1016/j.cclet.2019.12.001
15. [15]
  F. Xiong, X. Ling, X. Chen, et al., Nano Lett. 19 (2019) 3256-3266. doi: 10.1021/acs.nanolett.9b00824
16. [16]
  M. Li, X. Zhou, X. Zeng, et al., J. Mater. Chem. B 4 (2016) 547-556. doi: 10.1039/C5TB01964H
17. [17]
  E. Pérez-Herrero, A. Fernández-Medarde, Eur. J. Pharm. Biopharm. 93 (2015) 52-79. doi: 10.1016/j.ejpb.2015.03.018
18. [18]
  T. Sun, Y.S. Zhang, B. Pang, et al., Angew. Chem. Int. Ed. 53 (2014) 12320-12364.
19. [19]
  X. Feng, W. Xu, X. Xu, et al., Sci. China Chem. 64 (2021) 293-301. doi: 10.1007/s11426-020-9884-6
20. [20]
  J. Chen, Z. Jiang, W. Xu, et al., Nano Lett. 20 (2020) 6191-6198. doi: 10.1021/acs.nanolett.0c02515
21. [21]
  J. Xie, Y. Lu, B. Yu, et al., Chin. Chem. Lett. 31 (2020) 1173-1177. doi: 10.1016/j.cclet.2019.10.030
22. [22]
  C. Xian, Q. Yuan, Z. Bao, et al., Chin. Chem. Lett. 31 (2020) 19-27. doi: 10.1016/j.cclet.2019.03.052
23. [23]
  X. Feng, W. Xu, J. Liu, et al., Sci. Bull. 66 (2021) 362-373. doi: 10.1016/j.scib.2020.07.013
24. [24]
  X. Feng, W. Xu, X. Xu, et al., Sci. China Chem. 64 (2021) 293-301. doi: 10.1007/s11426-020-9884-6
25. [25]
  P. Yu, X. Li, G. Cheng, Chin. Chem. Lett. 32 (2021) 2127-2138. doi: 10.1016/j.cclet.2021.02.015
26. [26]
  X. Chen, L. Zhao, Y. Kang, et al., Front. Pharmacol. 9 (2018) 118. doi: 10.3389/fphar.2018.00118
27. [27]
  Y. Zhao, Z. Wang, Y. Jiang, et al., Cancer Lett. 313 (2011) 54-63. doi: 10.1016/j.canlet.2011.08.023
28. [28]
  Y. Guo, S.R. Kenney, C.Y. Muller, et al., Mol. Cancer Ther. 14 (2015) 2215-2227. doi: 10.1158/1535-7163.MCT-15-0419
29. [29]
  Y.Y. Hsieh, T.P. Liu, P.M. Yang, Pathol. Res. Pract. 215 (2019) 152373. doi: 10.1016/j.prp.2019.03.002
1. [1]
  Shuang Liang , Jianjun Yao , Dan Liu , Mengli Zhou , Yong Cui , Zhaohui Wang . Tumor-responsive covalent organic polymeric nanoparticles enhancing STING activation for cancer immunotherapy. Chinese Chemical Letters, 2025, 36(3): 109856-. doi: 10.1016/j.cclet.2024.109856
2. [2]
  Yiran Tao , Chunlei Dai , Zhaoxiang Xie , Xinru You , Kaiwen Li , Jun Wu , Hai Huang . Redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer. Chinese Chemical Letters, 2024, 35(8): 109170-. doi: 10.1016/j.cclet.2023.109170
3. [3]
  Ze Wang , Hao Liang , Annan Liu , Xingchen Li , Lin Guan , Lei Li , Liang He , Andrew K. Whittaker , Bai Yang , Quan Lin . Strength through unity: Alkaline phosphatase-responsive AIEgen nanoprobe for aggregation-enhanced multi-mode imaging and photothermal therapy of metastatic prostate cancer. Chinese Chemical Letters, 2025, 36(2): 109765-. doi: 10.1016/j.cclet.2024.109765
4. [4]
  Ling-Ling Wu , Xiangchuan Meng , Qingyang Zhang , Xiaowan Han , Feiya Yang , Qinghua Wang , Hai-Yu Hu , Nianzeng Xing . Heavy-atom engineered hypoxia-responsive probes for precisive photoacoustic imaging and cancer therapy. Chinese Chemical Letters, 2024, 35(4): 108663-. doi: 10.1016/j.cclet.2023.108663
5. [5]
  Chengde Wang , Liping Huang , Shanshan Wang , Lihao Wu , Yi Wang , Jun Dong . A distinction of gliomas at cellular and tissue level by surface-enhanced Raman scattering spectroscopy. Chinese Chemical Letters, 2024, 35(5): 109383-. doi: 10.1016/j.cclet.2023.109383
6. [6]
  Tong Tong , Lezong Chen , Siying Wu , Zhong Cao , Yuanbin Song , Jun Wu . Establishment of a leucine-based poly(ester amide)s library with self-anticancer effect as nano-drug carrier for colorectal cancer treatment. Chinese Chemical Letters, 2024, 35(12): 109689-. doi: 10.1016/j.cclet.2024.109689
7. [7]
  Zijian Jiang , Yuang Liu , Yijian Zong , Yong Fan , Wanchun Zhu , Yupeng Guo . Preparation of Nano Zinc Oxide by Microemulsion Method and Study on Its Photocatalytic Activity. University Chemistry, 2024, 39(5): 266-273. doi: 10.3866/PKU.DXHX202311101
8. [8]
  Chong Liu , Ling Li , Jiahui Gao , Yanwei Li , Nazhen Zhang , Jing Zang , Cong Liu , Zhaopei Guo , Yanhui Li , Huayu Tian . The study of antibacterial activity of cationic poly(β-amino ester) regulating by amphiphilic balance. Chinese Chemical Letters, 2025, 36(2): 110118-. doi: 10.1016/j.cclet.2024.110118
9. [9]
  Hongxia Li , Xiyang Wang , Du Qiao , Jiahao Li , Weiping Zhu , Honglin Li . Mechanism of nanoparticle aggregation in gas-liquid microfluidic mixing. Chinese Chemical Letters, 2024, 35(4): 108747-. doi: 10.1016/j.cclet.2023.108747
10. [10]
  Yixin Zhang , Ting Wang , Jixiang Zhang , Pengyu Lu , Neng Shi , Liqiang Zhang , Weiran Zhu , Nongyue He . Formation mechanism for stable system of nanoparticle/protein corona and phospholipid membrane. Chinese Chemical Letters, 2024, 35(4): 108619-. doi: 10.1016/j.cclet.2023.108619
11. [11]
  Wenlong Li , Feishi Shan , Qingdong Bao , Qinghua Li , Hua Gao , Leyong Wang . Supramolecular assembly nanoparticle for trans-epithelial treatment of keratoconus. Chinese Chemical Letters, 2024, 35(10): 110060-. doi: 10.1016/j.cclet.2024.110060
12. [12]
  Zhili Li , Qijun Wo , Dongdong Huang , Dezhong Zhou , Lei Guo , Yeqing Mao . Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups. Chinese Chemical Letters, 2024, 35(8): 109737-. doi: 10.1016/j.cclet.2024.109737
13. [13]
  Shaonan Liu , Shuixing Dai , Minghua Huang . The impact of ester groups on 1,8-naphthalimide electron transport material in organic solar cells. Chinese Journal of Structural Chemistry, 2024, 43(6): 100277-100277. doi: 10.1016/j.cjsc.2024.100277
14. [14]
  Botao QU , Qian WANG , Xiaogang NING , Yuxin ZHOU , Ruiping ZHANG . Deeply penetrating photoacoustic imaging in tumor tissues based on dual-targeted melanin nanoparticle. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 1025-1032. doi: 10.11862/CJIC.20230416
15. [15]
  Shenglan Zhou , Haijian Li , Hongyi Gao , Ang Li , Tian Li , Shanshan Cheng , Jingjing Wang , Jitti Kasemchainan , Jianhua Yi , Fengqi Zhao , Wengang Qu . Recent advances in metal-loaded MOFs photocatalysts: From single atom, cluster to nanoparticle. Chinese Chemical Letters, 2025, 36(1): 110142-. doi: 10.1016/j.cclet.2024.110142
16. [16]
  Xueqi Zhang , Han Gao , Jianan Xu , Min Zhou . Polyelectrolyte-functionalized carbon nanocones enable rapid and accurate analysis of Ag nanoparticle colloids. Chinese Chemical Letters, 2025, 36(4): 110148-. doi: 10.1016/j.cclet.2024.110148
17. [17]
  Yan Gao , Zi-Lin Song , Shuang Yu , Xiu-Li Zhao , Da-Wei Chen , Ming-Xi Qiao . Enhanced ferroptosis by a nanoparticle mimicking hemoglobin coordinate pattern with self-supplying hydrogen peroxide. Chinese Chemical Letters, 2025, 36(5): 110097-. doi: 10.1016/j.cclet.2024.110097
18. [18]
  Yunyan Li , Zimin Cai , Zhicheng Wang , Sifeng Zhu , Wendian Liu , Cheng Wang . Construction of biomimetic hybrid nanovesicles based on M1 macrophage-derived exosomes for therapy of cancer. Chinese Chemical Letters, 2025, 36(4): 109942-. doi: 10.1016/j.cclet.2024.109942
19. [19]
  Xiaohui Fu , Yanping Zhang , Juan Liao , Zhen-Hua Wang , Yong You , Jian-Qiang Zhao , Mingqiang Zhou , Wei-Cheng Yuan . Palladium-catalyzed enantioselective decarboxylation of vinyl cyclic carbamates: Generation of amide-based aza-1,3-dipoles and application to asymmetric 1,3-dipolar cycloaddition. Chinese Chemical Letters, 2024, 35(12): 109688-. doi: 10.1016/j.cclet.2024.109688
20. [20]
  Jijoe Samuel Prabagar , Kumbam Lingeshwar Reddy , Dong-Kwon Lim . Visible-light responsive gold nanoparticle and nano-sized Bi2O3-x sheet heterozygote structure for efficient photocatalytic conversion of N2 to NH3. Chinese Journal of Structural Chemistry, 2025, 44(4): 100564-100564. doi: 10.1016/j.cjsc.2025.100564

Get Citation

PDF

XML

Metrics

PDF Downloads(3)
Abstract views(1172)
HTML views(101)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142