Scholarlink

<p>Antisense oligonucleotides (ASOs) hold considerable promise for cancer gene therapy through targeted mRNA degradation. However, their biomedical application is hindered by inefficient delivery and limited visualization of biodistribution. Herein, we report a novel traceable afterglow nanoparticle platform for PLK1-targeted ASO delivery, representing the first reported integration of autofluorescence-free afterglow imaging with antisense therapeutics to enable non-invasive monitoring. Afterglow nanoparticle was assembled via nanoprecipitation of afterglow molecules (triple-anthracene derivatives) with surfactants, followed by polyethylenimine functionalization to enable ASO loading through electrostatic interactions, resulting in uniform nanoparticles with a favorable size distribution and high loading efficiency. <i>In vitro</i> evaluations revealed efficient cellular uptake, effective lysosomal escape and pronounced PLK1 silencing with substantial mRNA and protein downregulation, leading to marked induction of apoptosis in HeLa cells compared to free ASO. <i>In vivo</i> afterglow imaging demonstrated preferential tumor accumulation via the enhanced permeability and retention effect, with high signal-to-background ratios. In HeLa xenograft models, afterglow nanoparticle-mediated ASO delivery induced substantial tumor growth inhibition and widespread apoptosis, without detectable systemic toxicity as indicated by stable body weights and unremarkable organ histology. These findings highlight the potential of afterglow nanoparticles as a versatile platform for imaging-guided gene therapy, providing new avenues for enhanced precision in nucleic acid-based cancer treatments.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Afterglow nanoparticle-assisted PLK1-targeted antisense oligonucleotide delivery for cancer gene therapy

  • 期刊论文

  • 发表日期：

    2025年10月29日

查看全文
  • Wantao Tang,
  • Ting Tong,
  • Long Deng,
  • Qingpeng Zhang,
  • Yong Tan,
  • Yuzhen Yu,
  • Fengrong Lv,
  • Cheng Zhang,
  • Qiufang Gong,
  • Jingbo Dong,
  • Guosheng Song,
  • Chao Liang

摘要

Antisense oligonucleotides (ASOs) hold considerable promise for cancer gene therapy through targeted mRNA degradation. However, their biomedical application is hindered by inefficient delivery and limited visualization of biodistribution. Herein, we report a novel traceable afterglow nanoparticle platform for PLK1-targeted ASO delivery, representing the first reported integration of autofluorescence-free afterglow imaging with antisense therapeutics to enable non-invasive monitoring. Afterglow nanoparticle was assembled via nanoprecipitation of afterglow molecules (triple-anthracene derivatives) with surfactants, followed by polyethylenimine functionalization to enable ASO loading through electrostatic interactions, resulting in uniform nanoparticles with a favorable size distribution and high loading efficiency. In vitro evaluations revealed efficient cellular uptake, effective lysosomal escape and pronounced PLK1 silencing with substantial mRNA and protein downregulation, leading to marked induction of apoptosis in HeLa cells compared to free ASO. In vivo afterglow imaging demonstrated preferential tumor accumulation via the enhanced permeability and retention effect, with high signal-to-background ratios. In HeLa xenograft models, afterglow nanoparticle-mediated ASO delivery induced substantial tumor growth inhibition and widespread apoptosis, without detectable systemic toxicity as indicated by stable body weights and unremarkable organ histology. These findings highlight the potential of afterglow nanoparticles as a versatile platform for imaging-guided gene therapy, providing new avenues for enhanced precision in nucleic acid-based cancer treatments.