期刊
BIOMATERIALS
卷 32, 期 8, 页码 2222-2232出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.11.061
关键词
Co-delivery of siRNA and drug tumor-targeting; Electrostatic assembly; Gene silencing; Apoptosis; Chemotherapy
资金
- National Natural Science Foundation of China [50830107, 20728403, 20974129]
- 863 Programs of China [2009AA03Z310]
- Natural Science Foundation [9351027501000003]
- S&T Programs of Guangdong Province [2010B031500011]
- Guangzhou Scientific Project [2008Z1-D171]
- Open Project of State Key laboratory of Supramolecular Structure and Materials [SKLSSM200914]
Diblock copolymers (PEI-PCL) of poly(epsilon-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. (C) 2010 Elsevier Ltd. All rights reserved.
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