Toward targeted therapy in chemotherapy-resistant pancreatic cancer with a smart triptolide nanomedicine

Cheng Wang*, Biao Liu, Xuelian Xu, Bo Zhuang, Hongxia Li, Jiaqi Yin, Mengyi Cong, Wei Xu, Aiping LYU

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Chemoresistance is the major impediment for treating pancreatic cancer. Herb-derived compound triptolide (TP) can inhibit proliferation of chemo-resistant pancreatic cancer (CPC) cell lines through multiple mechanisms, which exhibited superior anticancer efficacy compared with gemcitabine. However, toxicity due to non-specific exposure to healthy tissues hindered its clinical translation. Herein we successfully achieved targeting CPC cells and avoiding exposure to healthy tissues for TP by nucleolin-specific aptamer (AS1411) mediated polymeric nanocarrier. We conjugated AS1411 aptamer to carboxy terminated poly(ethylene glycol)-block-poly(d, l-lactide) (HOOC-PEG-PDLLA), then prepared AS1411-PEG-PDLLA micelle loading TP (AS-PPT) through solid dispersion technique. AS-PPT showed more antitumor activity than TP and equivalent specific binding ability with gemcitabine-resistant human pancreatic cancer cell (MIA PaCa-2) to AS1411 aptamer in vitro. Furthermore, we studied the distribution of AS-PPT (Cy3-labed TP) at tissue and cellular levels using biophotonic imaging technology. The results showed AS1411 facilitated TP selectively accumulating in tumor tissues and targeting CPC cells. The lifetime of the MIA PaCa-2 cell-bearing mice administrated with AS-PPT was efficiently prolonged than that of the mice subjected to the clinical anticancer drug Gemzar® in vivo. Such work provides a new strategy for overcoming the drug resistance of pancreatic cancer.

Original languageEnglish
Pages (from-to)8360-8372
Number of pages13
JournalOncotarget
Volume7
Issue number7
DOIs
Publication statusPublished - 2016

Scopus Subject Areas

  • Oncology

User-Defined Keywords

  • AS1411
  • Chemoresistance
  • Pancreatic cancer
  • PEG-PDLLA
  • Triptolide

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