1. Academic Validation
  2. Polydopamine-Based Nanoparticles for Synergistic Chemotherapy of Prostate Cancer

Polydopamine-Based Nanoparticles for Synergistic Chemotherapy of Prostate Cancer

  • Int J Nanomedicine. 2024 Jul 3:19:6717-6730. doi: 10.2147/IJN.S468946.
Kebang Hu 1 Dongqi Zhang 1 Weiran Ma 2 Yanzhi Gu 2 Jiang Zhao 3 Xupeng Mu 4
Affiliations

Affiliations

  • 1 Department of Urology, Lequn Branch, The First Hospital of Jilin University, Changchun, 130031, People's Republic of China.
  • 2 College of Pharmacy, Jilin University, Changchun, 130021, People's Republic of China.
  • 3 Department of Urology, Xi'an First Hospital, Xi'an, 710002, People's Republic of China.
  • 4 Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, 130033, People's Republic of China.
Abstract

Introduction: Immune regulatory small molecule JQ1 can block its downstream effector PD-L1 pathway and effectively reverse the PD-L1 upregulation induced by doxorubicin (DOX). So the synergistic administration of chemotherapeutic drug DOX and JQ1 is expected to increase the sensitivity of tumors to immune checkpoint therapy and jointly enhance the body's own immunity, thus effectively killing tumor cells. Therefore, a Drug Delivery system loaded with DOX and JQ1 was devised in this study.

Methods: Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, Apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo.

Results: JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate Cancer cells, reduced the expression of Apoptosis related proteins and induced Apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo.

Conclusion: We have successfully prepared a multifunctional platform for synergistic prostate Cancer therapy.

Keywords

JQ1; PD-L1; chemotherapy; doxorubicin; polydopamine; prostate cancer.

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