A Glypican-1-Targeted and Gemcitabine-Loaded Biocompatible Nanoplatform for Pancreatic Cancer Near-Infrared Fluorescence/Magnetic Resonance Multimodal Imaging and Therapy

Background: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. The aim of this work were to design and evaluate glypican-1(GPC1) targeted, gemcitabine (GEM)-loaded multi-functional gold nanocarrier for near-infrared fluorescence (NIRF)/magnetic resonance (MR) imaging and targeted chemotherapy against pancreatic cancer.   Methods: GEM-loaded, anti-GPC1 antibody-modified gold nanocages (AuNCs) (GEM@HAuNCs) were prepared, and then conjugated with GPC1 antibody and Gd/Cy7  to create the multi-functional GPC1-GEM@HAuNCs-Cy7/Gd nanoparticles (GPC1-GEM-NPs). The targeting performance and effect on cell viablity of the GEM-GPC1-NPs were examined in vitro using BXPC-3, PANC-1 (GPC1 positive expression) and 293T (GPC1 negative expression) cells. The NIRF/ MR multimodal imaging properties and therapeutic activities of GPC1-GEM-NPs were tested in vivo in BXPC-3 xenograft mouse model. Findings: GPC1- GEM-NPs exhibited good biocompatibility, excellent colloidal stability, and targeting specificity to GPC1 over-expressing cells. Cell viability assays showed stronger growth inhibition of the GPC1-GEM-NPs against GPC1 positive pancreatic cells in comparison with GEM-NPs and GEM. Blood biochemical and histological analyses showed that the in vivo toxicity of GPC1- GEM-NPs was negligible. Both in vitro and in vivo studies demonstrated  that GPC1- GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1- GEM-NPs showed a higher tumor inhibitory effect compared with controls.   Interpretation: This theranostic nanoplatform provide early diagnostic and effective therapeutic potential for pancreatic cancer.   Funding Statement: This work is supported by the National Natural Science Foundation of China (Grant No. 81771899) and Primary Research & Development Plan of Jiangsu Province (BE2017772).   Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All animal experiments were approved and conducted according to the principles of the Nanjing University of Chinese Medicine Animal Care Committee (SYXK 2014-0001).