Your browser doesn't support javascript.
loading
Charge and Assembly Reversible Micelles Fueled by Intracellular ATP for Improved siRNA Transfection.
Zhou, Zhanwei; Li, Chenzi; Zhang, Minghua; Zhang, Qingyan; Qian, Chenggen; Oupicky, David; Sun, Minjie.
Afiliação
  • Zhou Z; State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , 24 Tong Jia Xiang , Nanjing 210009 , PR China.
  • Li C; State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , 24 Tong Jia Xiang , Nanjing 210009 , PR China.
  • Zhang M; State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , 24 Tong Jia Xiang , Nanjing 210009 , PR China.
  • Zhang Q; State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , 24 Tong Jia Xiang , Nanjing 210009 , PR China.
  • Qian C; State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , 24 Tong Jia Xiang , Nanjing 210009 , PR China.
  • Oupicky D; State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , 24 Tong Jia Xiang , Nanjing 210009 , PR China.
  • Sun M; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences , University of Nebraska Medical Center , Omaha , Nebraska 68198 , United States.
ACS Appl Mater Interfaces ; 10(38): 32026-32037, 2018 Sep 26.
Article em En | MEDLINE | ID: mdl-30179452
Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA. In this study, we propose a new strategy by the combination of micelles disassembly and separated polycations charge reversal. FPBA (3-fluoro-4-carboxyphenylboronic acid) grafted PEI 1.8 k (polyethylenimine) as the polycations of PEI-FPBA and dopamine (with diol-containing moiety) conjugated with cholesterol as the hydrophobic part (Chol-Dopa). The PFCDM micelles was assembled by PEI-FPBA and Chol-Dopa, based on the FPBA-Dopa conjugation. The prepared PFCDM showed strong siRNA loading ability and superior stability in the presence of PBS or serum. Besides, the PFCDM exhibited excellent ATP sensibility. The intracellular ATP could effectively trigger the disassembly of micelles and charge reversal of PEI-FPBA, resulting in the burst release of siRNA in the cytosol. With the property of extracellular stability and intracellular instability, PFCDM displayed good performance on in vitro and in vivo luciferase silencing on 4T1 cells. It should also be noted that the assembly of low molecular weight PEI was relatively safe to cells compared with 25 k PEI. To sum up, the ATP-fueled assembly and charge reversible micelles gave examples for polyplexes to achieve better stability and on demand cargo release at the same time and shows potential to be used for in vitro and in vivo siRNA transfection.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transfecção / Trifosfato de Adenosina / RNA Interferente Pequeno / Micelas Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transfecção / Trifosfato de Adenosina / RNA Interferente Pequeno / Micelas Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article