A GPC1-targeted and gemcitabine-loaded Biocompatible Nanoplatform for Pancreatic Cancer Multimodal Imaging and Therapy

Abstract

Aim: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. Materials & methods: This work successfully designs and evaluates GPC1-targeted, gemcitabine (GEM)-loaded multifunctional gold nanocarrier for near-infrared fluorescence (NIRF)/MRI and targeted chemotherapy against pancreatic cancer in vitro and in vivo. Results: Blood biochemical and histological analyses show that the in vivo toxicity of GPC1-GEM-nanoparticles (NPs) was negligible. Both in vitro and in vivo studies demonstrate that GPC1-GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1-GEM-NPs shows a higher tumor inhibitory effect compared with controls. Conclusion: This novel theranostic nanoplatform provides early diagnostic and effective therapeutic potential for pancreatic cancer.

Graphical abstract

Development and functionality of the GPC1-GEM-NPs. (A) The preparation of GPC1-GEM-NPs. (B) GPC1-GEM-NPs as tumor-targeted multifunctional theranostic nanoplatforms for multimodal imaging and therapy by GPC1-mediated antibody–antigen combination. ① Coincubation; ② Au–S coupling chemistry; ③ amidation reaction; ④ antibody–antigen combination; ⑤ endocytosis; ⑥ endosome escape; ⑦ pH/hyaluronidase response.

Keywords:

• gemcitabine
• GPC1
• multimodal imaging
• targeted therapy
• theranostic nanoplatform

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Author contributions

All the authors listed contributed to the final manuscript in the following manner: literature search was completed by WL Qiu; study design by WL Qiu and ZQ Wang; data acquisition by WL Qiu, HF Zhang, LN Song, WJ Cui, S Ren, YJ Wang and K Guo; data analysis and interpretation by WL Qiu, R Chen and ZQ Wang; drafting of the manuscript by WL Qiu; critical revision of the manuscript by DH Li and ZQ Wang; obtained funding by ZQ Wang.

Financial & competing interests disclosure

This work is supported by the National Natural Science Foundation of China (grant no. 81771899) and Primary Research & Development Plan of Jiangsu Province (BE2017772). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal experiments were approved and conducted according to the principles of the Nanjing University of Chinese Medicine Animal Care Committee (SYXK 2014-0001). The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.