超声诱导微泡空化联合紫杉醇负载纳米颗粒体外清除PC-3细胞

Pub Date : 2021-10-06 DOI:10.1142/s1793984421500069
Ziqi Wang, Chuanrong Chen, Penglin Zou, Yu-Cheng Tao, F. Gao, Chao Jia, Long Liu, Y. Duan, Qiusheng Shi
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引用次数: 1

摘要

去势抵抗性前列腺癌(CRPC)及其转移是导致前列腺癌高死亡率的主要原因。目前,以紫杉醇(paclitaxel, PTX)为基础的化疗药物是治疗CRPC的一线药物,但这种治疗效果不佳,副作用严重,这可能是由于静脉注射化疗药物难以在肿瘤部位聚集。因此,迫切需要一种安全有效的给药载体来提高化疗药物对CRPC的治疗效果。甲氧基聚乙二醇-聚乳酸-乙醇酸-聚赖氨酸(mPEG-PLGA-PLL)纳米颗粒(NPs)对卵巢癌和胰腺癌具有较高的药物包封效率和良好的治疗效果,但其治疗CRPC的研究较少。为了扩大mPEG-PLGA-PLL NPs的应用范围,本研究合成了加载PTX的mPEG-PLGA-PLL NPs (PTX-NPs)。合成的PTX-NPs粒径均匀,无明显聚集。PTX- nps可被PC-3细胞摄取,显著促进PTX对细胞的增殖和凋亡抑制作用,降低CDK6、Cyclin D1和Bcl-2(细胞周期蛋白和一种凋亡抑制剂)的表达水平,超声诱导的微泡空化(UIMC)可进一步增强这些作用。本研究为CRPC的处理提供了一种新的纳米载体,为今后的进一步研究奠定了基础。
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Ultrasound-Induced Microbubble Cavitation Combined with Paclitaxel-Loaded Nanoparticles for the Elimination of PC-3 Cells in vitro
Castration-resistant prostate cancer (CRPC) and its metastases are the main reasons for the high mortality of prostate cancer. Currently, paclitaxel (PTX)-based chemotherapeutics are used as first-line drugs to treat CRPC, but this treatment does not show good effects and is accompanied by serious side effects, which may be because intravenously injected chemotherapeutic drugs have difficulties gathering at the tumor site. Therefore, a safe and effective drug delivery carrier is urgently needed to enhance the therapeutic effects of chemotherapeutic drugs against CRPC. Methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles (NPs) have shown high drug encapsulation efficiency and good therapeutic effects against ovarian cancer and pancreatic cancer, but there are few studies on their treatment against CRPC. To expand the applications of mPEG-PLGA-PLL NPs, in this study, mPEG-PLGA-PLL NPs loaded with PTX (PTX-NPs) were synthesized. The synthesized PTX-NPs had a uniform particle size and no obvious aggregation. PTX-NPs can be uptaked by PC-3 cells, which significantly promotes the inhibition of proliferation and apoptosis effects of PTX on cells and reduces the expression levels of CDK6, Cyclin D1 and Bcl-2 (cyclins and an apoptosis inhibitor), and these effects can be further enhanced by ultrasound-induced microbubble cavitation (UIMC). Our research provides a new nanocarrier for the treatment of CRPC, laying the foundation for further research in the future.
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