Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

Qu, Zhen; Ren, Yuning; Shen, Huan; Shi, Lijie; Tong, Deyong

doi:10.2147/dddt.s306684

Cited by 16 publications

(8 citation statements)

References 55 publications

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“…Unlike many drug delivery systems against PCs at present, combination therapy requires that the two chemotherapeutic drugs, which are both hydrophobic, be packaged into the same hydrophobic cavity. The two are crowded with each other, leading to limited drug loading and failure to meet the effective dosage [ 36 , 37 , 38 ]. Moreover, the effective dose of siRNA itself is much lower than that of chemotherapeutic drugs [ 19 ], so this further reduces the pressure on our designed delivery system to contain drugs.…”

Section: Discussionmentioning

confidence: 99%

Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment

et al. 2022

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Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment

et al. 2022

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“…Qu et al conjugated cabazitaxel onto HA polymer and mixed with soybean lecithin (SL). 1,2‐Distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐carboxy (polyethylene glycol)2000 (DSPE‐PEG) was also used to form polymer–hybrid nanoparticles (Z. Qu et al, 2021). Orlistat (ORL), an effective fatty acid synthase (FASN), was co‐loaded with cabazitaxel‐prodrug, and was investigated on taxane‐sensitive cancer cells.…”

Section: The Development Of Cabazitaxel Formulationsmentioning

confidence: 99%

Current development of cabazitaxel drug delivery systems

Sun

Lovell

Zhang

2022

WIREs Nanomed Nanobiotechnol

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The second-generation taxane cabazitaxel has been clinically approved for the treatment of metastatic castration-resistant prostate cancer after docetaxel failure. Compared with the first-generation taxanes paclitaxel and docetaxel, cabazitaxel has potent anticancer activity and is less prone to drug resistance due to its lower affinity for the P-gp efflux pump. The relatively high hydrophobicity of cabazitaxel and the poor aqueous colloidal stability of the commercial formulation, following its preparation for injection, presents opportunities for new cabazitaxel formulations with improved features. This review provides an overview of cabazitaxel drug formulations and hydrophobic taxane drug delivery systems in general, and particularly focuses on emerging cabazitaxel delivery systems discovered in the past 5 years.

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“… 24 An HA-decorated, cabazitaxel and orlistat co-loaded nano-system was developed by researchers to treat prostate cancer. 25 …”

Section: Introductionmentioning

confidence: 99%

“…24 An HA-decorated, cabazitaxel and orlistat co-loaded nano-system was developed by researchers to treat prostate cancer. 25 In this study, 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 were constructed by the self-assembling of GE-NPs and HA-NPs.…”

Section: Introductionmentioning

confidence: 99%

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

Zhao¹,

Wang²,

Guo³

et al. 2022

DDDT

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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.

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Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

Cited by 16 publications

References 55 publications

Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment

Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment

Current development of cabazitaxel drug delivery systems

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

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