Silica/gold nanoplatform combined with a thermosensitive gel for imaging-guided interventional therapy in PDX of pancreatic cancer

Abstract

Imaging-guided interventional therapy is a promising means of minimally invasive and targeted drug delivery for patients with advanced pancreatic cancer. The effectiveness of the method depends on clear imaging and complete removal of cancer cells, especially peripheral infiltration and distant metastasis, to prevent recurrence. We synthesized hollow mesoporous silica-based nanoparticles, Gem-PFH-Au star-HMS-IGF1, with gemcitabine (Gem) and perfluorohexane (PFH) encapsulated internally, gold nanostars (Au NSs) and insulin-like growth factor-1 (IGF1) modified outwardly, to enhance multimode ultrasound (US)/computed tomography (CT)/photoacoustic (PA)/thermal imaging, guide photothermal therapy, and evaluate the effect in real time. We also prepared a type of thermosensitive gel that solidified at body temperature to facilitate the controlled release of Gem and achieve a single-administration interventional therapy. A patient-derived xenograft (PDX) mouse model was established in this study. The PDX was precisely ablated by photothermal therapy under the guidance of US/CT/PA imaging, and the residual pancreatic cancer cells were completely inhibited by Gem to prevent recurrence. This strategy ingeniously simulated the approach of surgical resection and postoperative chemotherapy in clinical procedures to treat malignancy and paves the way for interventional therapy. © 2019 The Authors