The synergistic effect of hierarchical assemblies of siRNA and chemotherapeutic drugs co-delivered into hepatic cancer cells

Nuo Cao, Du Cheng, Seyin Zou, Hua Ai, Jinming Gao, Xintao Shuai

Research output: Contribution to journalArticle

169 Scopus citations


Diblock copolymers (PEI-PCL) of poly(ε-caprolactone) (PCL) and linear poly(ethylene imine) (PEI) were synthesized and assembled to biodegradable nano-carriers for co-delivery of BCL-2 siRNA and doxorubicin (DOX). Folic acid as a tumor-targeting ligand was conjugated to the polyanion, poly(ethylene glycol)-block-poly(glutamic acid) (FA-PEG-PGA). Driven by the electrostatic interaction, FA-PEG-PGA was coated onto the surface of the cationic PEI-PCL nanoparticles pre-loaded with siRNA and DOX, potentiating a ligand-directed delivery to human hepatic cancer cells Bel-7402. At certain N/P and C/N ratios (N/P: PEI-PCL nitrogen to siRNA phosphate; C/N: FA-PEG-PGA carboxyl to PEI-PCL amine), the nanoparticles exhibited not only high transfection efficiency but also ideally controlled release of drug. Compared to non-specific delivery, the folate-targeted delivery of BCL-2 siRNA resulted in more significant gene suppression at both the BCL-2 mRNA and protein expression levels, inducing cancer cell apoptosis and improving the therapeutic efficacy of the co-administered DOX. Herein we demonstrated that co-loading siRNA and small molecular drug in a multifunctional hierarchical nano-assembly enabled simultaneously delivering siRNA and drug into the same cancer cells, yielding synergistic effect of RNA interference and chemotherapy in cancer.

Original languageEnglish (US)
Pages (from-to)2222-2232
Number of pages11
Issue number8
Publication statusPublished - Mar 2011



  • Apoptosis
  • Chemotherapy
  • Co-delivery of siRNA and drug
  • Electrostatic assembly
  • Gene silencing
  • Tumor-targeting

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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