title: The synergistic effect of hierarchical assemblies of siRNA and chemotherapeutic drugs co-delivered into hepatic cancer cells.
abstract: 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.
authors.affiliation: Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Nuo
authors.initials: N
authors.lastname: Cao
authors.forename: Du
authors.initials: D
authors.lastname: Cheng
authors.forename: Seyin
authors.initials: S
authors.lastname: Zou
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008422:Materials Testing; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D002412:Cations; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D004317:Doxorubicin