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Background <p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Regardless of surgical resection, chemotherapy acts as the first-line treatment for PDAC. However, the clinical outcomes are severely compromised by insufficient tumour-specific targeting, chemoresistance, and systemic toxicity. Thus, new synergistic therapeutic strategies are urgently needed to improve therapeutic efficacy of PDAC.</p> Purpose <p>This study developed a glypican-1 (GPC1)-targeted and low-intensity focused ultrasound (LIFU)-responsive nanoplatform for visualized treatment against PDAC.</p> Methods <p>This nanoplatform, termed GCPIP, integrated glypican-1-antibody (GPC1-Ab)-guided tumour-specific targeting, perfluoropentane (PFP)-driven acoustic imaging, ultrasound targeted nanobubble destruction (UTND)-triggered drug release, paclitaxel (PTX)-mediated chemotherapy and sonosensitizer-assisted sonodynamic therapy (SDT).</p> Results <p>GCPIP exhibited favourable physicochemical properties as a delivery system, showing excellent stability, responsive drug release behaviour, and robust ROS-generating capacity. In vitro studies revealed that GCPIP exhibited outstading tumour-targeting capability and potent inhibitory activity against PDAC tumour cells. Near-infrared fluorescence (NIRF) imaging in vivo demonstrated that GCPIP displayed a biodistribution profile broadly consistent with typical metabolic fate of nanoparticles, enabling preferential intratumoural accumulation. Leveraging acoustic droplet vaporization (ADV) effect of PFP, ultrasound (US) imaging further allowed real-time visualization of the uptake and spatial distribution of GCPIP within the tumour. Importantly, GCPIP elicited a pronounced synergistic antitumour effect upon LIFU, as evidenced by substantial inhibition in both tumour volume and tumour weight. Additionally, GCPIP exhibited favourable biosafety in vivo.</p> Conclusion <p>GCPIP successfully achieved US imaging, tumour-specific drug delivery, spatiotemporally controlled drug release, and amplified chemo-sonodynamic therapy, providing a promising strategy to overcome chemoresistance of PDAC and reduce systemic toxicity.</p> Graphical abstract <p></p>

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Investigation of a GPC1-targeted and LIFU-responsive nanoplatform with ADV effect for visualized chemo-sonodynamic therapy against pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月1日

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  • Bo Ren,
  • Gang Quan,
  • Hanmei Li,
  • Litao Ye,
  • Xin Xie,
  • Jinhong Yu,
  • Jian Xu,
  • Jingdong Li,
  • CharngChoon Wong

摘要

Background

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Regardless of surgical resection, chemotherapy acts as the first-line treatment for PDAC. However, the clinical outcomes are severely compromised by insufficient tumour-specific targeting, chemoresistance, and systemic toxicity. Thus, new synergistic therapeutic strategies are urgently needed to improve therapeutic efficacy of PDAC.

Purpose

This study developed a glypican-1 (GPC1)-targeted and low-intensity focused ultrasound (LIFU)-responsive nanoplatform for visualized treatment against PDAC.

Methods

This nanoplatform, termed GCPIP, integrated glypican-1-antibody (GPC1-Ab)-guided tumour-specific targeting, perfluoropentane (PFP)-driven acoustic imaging, ultrasound targeted nanobubble destruction (UTND)-triggered drug release, paclitaxel (PTX)-mediated chemotherapy and sonosensitizer-assisted sonodynamic therapy (SDT).

Results

GCPIP exhibited favourable physicochemical properties as a delivery system, showing excellent stability, responsive drug release behaviour, and robust ROS-generating capacity. In vitro studies revealed that GCPIP exhibited outstading tumour-targeting capability and potent inhibitory activity against PDAC tumour cells. Near-infrared fluorescence (NIRF) imaging in vivo demonstrated that GCPIP displayed a biodistribution profile broadly consistent with typical metabolic fate of nanoparticles, enabling preferential intratumoural accumulation. Leveraging acoustic droplet vaporization (ADV) effect of PFP, ultrasound (US) imaging further allowed real-time visualization of the uptake and spatial distribution of GCPIP within the tumour. Importantly, GCPIP elicited a pronounced synergistic antitumour effect upon LIFU, as evidenced by substantial inhibition in both tumour volume and tumour weight. Additionally, GCPIP exhibited favourable biosafety in vivo.

Conclusion

GCPIP successfully achieved US imaging, tumour-specific drug delivery, spatiotemporally controlled drug release, and amplified chemo-sonodynamic therapy, providing a promising strategy to overcome chemoresistance of PDAC and reduce systemic toxicity.

Graphical abstract