Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells.

Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells.
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转铁蛋白轴承,玉米醇溶蛋白为基础的混合脂质纳米颗粒的药物和基因输送到前列腺癌细胞。

DOI:
10.3390/pharmaceutics15112643
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发表时间:
2023-11-20
期刊:
影响因子:
5.4
通讯作者:
Dufès C
Dufès C
中科院分区:
医学2区
文献类型:
--
作者:
Maeyouf K;Sakpakdeejaroen I;Somani S;Meewan J;Ali-Jerman H;Laskar P;Mullin M;MacKenzie G;Tate RJ;Dufès C

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基因疗法在治疗对常规疗法无反应的前列腺癌方面具有很大的前景。然而,缺乏可以在靶向肿瘤的同时运输治疗性DNA和药物而不损害健康组织的递送系统提出了重大挑战。本研究的目的是探索新型混合脂质纳米粒的潜力,由生物相容性玉米醇溶蛋白和共轭的癌症靶向配体转铁蛋白。这些纳米颗粒被设计为捕获抗癌药物多西他赛并携带质粒DNA,目的是改善治疗有效载荷向前列腺癌细胞的递送,从而增强其抗增殖功效和基因表达水平。这些携带转铁蛋白、基于玉米醇溶蛋白的混合脂质纳米粒有效地包埋多西他赛,导致PC-3和LNCaP癌细胞的摄取增加,并在多西他赛浓度超过1 μg/mL时显著增强抗增殖功效。此外,它们表现出熟练的DNA缩合,在聚合物-DNA重量比为1500:1和2000:1时超过80%。这导致在所有测试的细胞系中基因表达增加,在LNCaP细胞中,最高转染水平比对照组观察到的高11倍。因此,这些新的转铁蛋白轴承,玉米醇溶蛋白为基础的混合脂质纳米粒子显示出良好的潜力,作为药物和基因传递系统的前列腺癌治疗。
Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer–DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy.
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