Investigation of a GPC1-targeted and LIFU-responsive nanoplatform with ADV effect for visualized chemo-sonodynamic therapy against pancreatic ductal adenocarcinoma
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Published on: December 1, 2016
Bo Ren1,2, Gang Quan3,4, Hanmei Li1
1Department of Ultrasound, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
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.
