关键词: Black phosphorus nanosheets PTEN Prostate cancer RNA delivery ceRNA mechanism

Mesh : Male PTEN Phosphohydrolase / genetics metabolism Humans Prostatic Neoplasms / genetics therapy Phosphorus / chemistry Nanostructures / chemistry MicroRNAs / genetics Cell Line, Tumor PC-3 Cells RNA, Long Noncoding / genetics metabolism Polyethyleneimine / chemistry Animals Gene Transfer Techniques Gene Expression Regulation, Neoplastic / drug effects RNA, Competitive Endogenous

来  源:   DOI:10.1186/s12951-024-02659-2   PDF(Pubmed)

Abstract:
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.
摘要:
背景:前列腺癌(PCa)在全球男性中发病率很高,几乎所有PCa患者都进展到雄激素非依赖性阶段,缺乏有效的治疗措施。PTENP1,一种长非编码RNA,已显示通过竞争性内源性RNA(ceRNA)机制挽救PTEN表达来抑制肿瘤生长。然而,PTENP1由于酶的快速降解而被限制在PCa的处理中,细胞内摄取差,和过长的碱基序列要合成。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。
结果:以PTENP1序列为模板,随机分成4个长度约1000个核苷酸碱基的片段,合成4个不同的RNA片段作为基因药物,并加载到聚乙烯亚胺(PEI)修饰的BP纳米片上以构建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,并通过靶向PTENmRNA的竞争性结合microRNA(miRNA)提高PTEN表达,最终发挥抗肿瘤作用。
结论:因此,这项研究表明,BP-PEI@RNA是PCa治疗的一个有前途的基因治疗平台。
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