Preparation of Dual-Template Epitope Imprinted Polymers for Targeted Fluorescence Imaging and Targeted Drug Delivery to Pancreatic Cancer BxPC-3 Cells

  • ACS Appl Mater Interfaces. 2019 Sep 4;11(35):32431-32440. doi: 10.1021/acsami.9b11533.
Chao Jia  1 Man Zhang  2 Yan Zhang  3 Zi-Bo Ma  1 Nan-Nan Xiao  3 Xi-Wen He  1 Wen-You Li  1  4 Yu-Kui Zhang  1  5
Affiliations
  • 1. College of Chemistry, Research Center for Analytical Sciences, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition , Nankai University , Tianjin 300071 , China.
  • 2. College of Pharmacy , Nankai University , Tianjin 300071 , China.
  • 3. State Key Laboratory of Medicinal Chemical Biology , Nankai University , Tianjin 300350 , China.
  • 4. Collaborative Innovation Center of Chemical Science and Engineering , Tianjin 300071 , China.
  • 5. National Chromatographic Research and Analysis Center , Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023 , China.
Abstract

Molecularly imprinted Polymers were commonly used for drug delivery. However, single-template molecularly imprinted Polymers often fail to achieve both drug delivery and precise targeting. To address this issue, a dual-template molecularly imprinted polymer nanoparticle used for targeted diagnosis and drug delivery for pancreatic Cancer BxPC-3 cells (FH-MIPNPs) was prepared. In the FH-MIPNPs, the 71-80 peptide of human fibroblast growth-factor-inducible 14 modified with glucose (Glu-FH) and bleomycin (BLM) were used as templates simultaneously, so that the FH-MIPNPs could load BLM and bind to the BxPC-3 cells, which overexpress human fibroblast growth-factor-inducible 14 (FN14). Targeted imaging experiments in vitro show that the FH-MIPNPs could specifically target BxPC-3 cells and that there is no targeting effect on cells without expression of FN14. In vivo antitumor experiment results demonstrated that the FH-MIPNP-loaded BLM (FH-MIPNPs/BLM) could inhibit the growth of xenografts tumor of BxPC-3 (tumor volume increased to 1.05×), which shows that FH-MIPNPs/BLM had obvious targeted therapeutic effect compared to the Other three control groups of BLM, FH-NIPNPs/BLM, and physiological saline (tumor volume increased to 1.5×, 1.6×, and 2.4×, respectively). What is more, FH-MIPNPs have low biotoxicity through toxicity experiments in vitro and in vivo, which is favorable toward making molecularly imprinted Polymers an effective platform for tumor-targeted imaging and therapy.

Keywords
drug delivery; imaging; in vivo; molecular imprinting; target.
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