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. 2022 Aug 11:16:2683-2693.
doi: 10.2147/DDDT.S366622. eCollection 2022.

Prostate Cancer Therapy Using Docetaxel and Formononetin Combination: Hyaluronic Acid and Epidermal Growth Factor Receptor Targeted Peptide Dual Ligands Modified Binary Nanoparticles to Facilitate the in vivo Anti-Tumor Activity

Zhaoqiang Dong  1 , Yuzhen Wang  2 , Jing Guo  3 , Chuan Tian  4 , Wengu Pan  4 , Hongwei Wang  4 , Jieke Yan  4
Affiliations

Prostate Cancer Therapy Using Docetaxel and Formononetin Combination: Hyaluronic Acid and Epidermal Growth Factor Receptor Targeted Peptide Dual Ligands Modified Binary Nanoparticles to Facilitate the in vivo Anti-Tumor Activity

Zhaoqiang Dong et al. Drug Des Devel Ther. .

Abstract

Objective: To evaluate the prostate cancer therapy efficiency of the synergistic combination docetaxel (DTX) and formononetin (FMN) in one nano-sized drug delivery system. Hyaluronic acid (HA) and epidermal growth factor receptor-targeted peptide (GE11) dual ligands were applied to modify the nano-systems.

Methods: In this study, GE11-modified nanoparticles (GE-NPs) were applied for the loading of DTX, and HA-decorated NPs (HA-NPs) were used to encapsulate FMN. HA and GE11 dual ligand-modified binary nanoparticles (HAGE-DTX/FMN-NPs) were constructed by the self-assembling of GE-NPs and HA-NPs. The anti-PCa ability of the system was evaluated in vitro on PC-3 human prostate carcinoma cells (PC3 cells) and in vivo on PC3 tumor-bearing mice in comparison with single NPs and free drugs formulations.

Results: HA/GE-DTX/FMN-NPs were nano-sized particles with smaller particles coating on the inner core and achieved a size of 189.5 nm. HA/GE-DTX/FMN-NPs showed a cellular uptake efficiency of 59.6%, and a more efficient inhibition effect on PC3 cells compared with single ligand-modified NPs and free drugs. HA/GE-DTX/FMN-NPs showed significantly higher tumor inhibition efficiency than their single drug-loaded counterparts and free drugs.

Conclusion: HA/GE-DTX/FMN-NPs have a synergistic anti-tumor effect and also could the reduce unexpected side effects during the cancer therapy. It could be used as a promising anti-PCa system.

Keywords: binary nanoparticles; docetaxel; epidermal growth factor receptor; formononetin; hyaluronic acid; prostate cancer.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Scheme graphs and TEM images of GE-DTX-NPs (A), HA-FMN-NPs (B), and HA/GE-DTX/FMN-NPs (C).
Figure 2
Figure 2
Stability of NPs during storage at 4°C (A), and in the presence of fetal bovine serum (FBS, 10%, v/v) at 37°C for 72 h (B). Data are presented as means ± standard deviation (n=3).
Figure 3
Figure 3
In vitro DTX (A) and FMN (B) release performed using dialysis method. Data are presented as means ± standard deviation (n=3).
Figure 4
Figure 4
Cellular uptake efficiency of the coumarin 6-loaded NPs in PC3 cells: fluorescence images (A) and quantified by flow cytometer (B). Bars stand for 50 μm. Data are presented as means ± standard deviation (n=3). *P < 0.05.
Figure 5
Figure 5
In vitro cytotoxicity of different formulations on PC3 cells (A) and RWPE-1 cells (B). CI values versus Fa at different DTX to FMN ratios (C). Data are presented as means ± standard deviation (n=3). *P < 0.05.
Figure 6
Figure 6
In vivo anti-tumor efficacy of different formulations in mice bearing human prostate cancer model: Tumor volumes and images. Data are presented as means ± standard deviation (n=8). *P < 0.05.
Figure 7
Figure 7
In vivo DTX (A) and FMN (B) tissue distribution. Data are presented as means ± standard deviation (n=8). *P < 0.05.
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