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<p>Enzalutamide (ENZ) resistance has emerged as a critical therapeutic hurdle in advanced prostate cancer (PCa) management. This study aims to investigate the potential of ultrasound-guided nanobubble-mediated co-delivery of small interfering RNA targeting fibroblast growth factor receptor 1 (siFGFR1) and ENZ to overcome ENZ resistance in PCa. The nanobubbles (PFP-ENZ@siRNA-NBs-RGD) were characterized for particle size, zeta potential, and morphology. Their biocompatibility was confirmed via hemolysis assays. In vitro, selective targeting of PCa cells was observed, and the system exhibited minimal toxicity to normal cells while effectively inhibiting ENZ-resistant PCa. Under ultrasound, ENZ and siFGFR1 downregulated AR/PSA, p-PI3K/p-Akt/p-mTOR and P-gp, and modulated apoptotic-related proteins (Caspase-3/Bax upregulated, Bcl-2 downregulated). Additionally, apoptosis rates were significantly increased. In vivo, tumor growth was reduced, with concurrent suppression of p-PI3K/p-Akt/p-mTOR, P-gp downregulation, and apoptotic-related protein modulation in tumor tissues, validating in vitro mechanisms. Moreover, no adverse effects were observed. These findings suggest that the ultrasound-guided co-delivery of siFGFR1 and ENZ via nanobubbles represents a promising strategy to combat ENZ-resistant prostate cancer.</p>

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Tumor-targeted nanobubbles delivering PFP/siFGFR1 for US imaging and overcoming enzalutamide-resistant in prostate cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Weimin Dong,
  • Zhiming Zhang,
  • Zhengming Su,
  • Henghui Zhang,
  • Yiqiao Huang,
  • Guohao Zeng,
  • Maozhi Xiao,
  • Kaiyue Tang,
  • Weide Zhong,
  • Xianhan Jiang

摘要

Enzalutamide (ENZ) resistance has emerged as a critical therapeutic hurdle in advanced prostate cancer (PCa) management. This study aims to investigate the potential of ultrasound-guided nanobubble-mediated co-delivery of small interfering RNA targeting fibroblast growth factor receptor 1 (siFGFR1) and ENZ to overcome ENZ resistance in PCa. The nanobubbles (PFP-ENZ@siRNA-NBs-RGD) were characterized for particle size, zeta potential, and morphology. Their biocompatibility was confirmed via hemolysis assays. In vitro, selective targeting of PCa cells was observed, and the system exhibited minimal toxicity to normal cells while effectively inhibiting ENZ-resistant PCa. Under ultrasound, ENZ and siFGFR1 downregulated AR/PSA, p-PI3K/p-Akt/p-mTOR and P-gp, and modulated apoptotic-related proteins (Caspase-3/Bax upregulated, Bcl-2 downregulated). Additionally, apoptosis rates were significantly increased. In vivo, tumor growth was reduced, with concurrent suppression of p-PI3K/p-Akt/p-mTOR, P-gp downregulation, and apoptotic-related protein modulation in tumor tissues, validating in vitro mechanisms. Moreover, no adverse effects were observed. These findings suggest that the ultrasound-guided co-delivery of siFGFR1 and ENZ via nanobubbles represents a promising strategy to combat ENZ-resistant prostate cancer.