研究动态
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基于黑磷纳米片的 RNA 递送系统,通过 CeRNA 机制增加肿瘤抑制基因 PTEN 的表达水平,用于前列腺癌治疗。

A black phosphorus nanosheet-based RNA delivery system for prostate cancer therapy by increasing the expression level of tumor suppressor gene PTEN via CeRNA mechanism.

发表日期:2024 Jul 04
作者: Shunye Su, Leyi Liu, Qingfeng Fu, Minghao Ma, Na Yang, Ting Pan, Shengyong Geng, Xue-Feng Yu, Jianqiang Zhu
来源: JOURNAL OF NANOBIOTECHNOLOGY

摘要:

前列腺癌(PCa)在全球男性中发病率较高,几乎所有PCa患者均进展至雄激素非依赖期,缺乏有效的治疗措施。 PTENP1 是一种长链非编码 RNA,已被证明可以通过竞争性内源 RNA (ceRNA) 机制拯救 PTEN 表达来抑制肿瘤生长。然而,PTENP1由于酶降解速度快、细胞内摄取差、合成的碱基序列过长等原因限制了其在PCa治疗中的应用。考虑到人工纳米材料在药物装载和运输方面的独特优势,本研究采用黑磷(BP)纳米片作为基因药物载体。以PTENP1序列为模板,将其随机分为四个长度片段约1000个核苷酸碱基合成四种不同的RNA片段作为基因药物,并将其负载到聚乙烯亚胺(PEI)修饰的BP纳米片上构建BP-PEI@RNA递送平台。 RNA可以通过BP-PEI纳米片有效地递送到PC3细胞中,并通过竞争性结合靶向PTEN mRNA的microRNA(miRNA)来提高PTEN表达,最终发挥抗肿瘤作用。因此,本研究证明BP-PEI@RNA是一种有前途的 PCa 治疗基因治疗平台。© 2024。作者。
Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study.The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects.Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.© 2024. The Author(s).