Thermoresponsive pegylated bubble liposome nanovectors for efficient siRNA delivery via endosomal escape

被引:21
作者
Alamoudi, Kholod [1 ]
Martins, Patricia [1 ]
Croissant, Jonas G. [1 ]
Patil, Sachin [1 ]
Omar, Haneen [1 ]
Khashab, Niveen M. [1 ]
机构
[1] King Abdullah Univ Sci & Technol, Smart Hybrid Mat Lab, Adv Membranes & Porous Mat Ctr, Thuwal, Saudi Arabia
关键词
bubble generation; endosomal escape; gene silencing; lipoplex; liposome; multidrug-resistant cell; nanomedicine; siRNA delivery; MESOPOROUS ORGANOSILICA NANOPARTICLES; MEDIATED GENE-TRANSFER; SYSTEMIC DELIVERY; DRUG-DELIVERY; IN-VITRO; ULTRASOUND EXPOSURE; CANCER; NANOMEDICINE; CHOLESTEROL; MECHANISM;
D O I
10.2217/nnm-2017-0021
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: Improving the delivery of siRNA into cancer cells via bubble liposomes. Designing a thermoresponsive pegylated liposome through the introduction of ammonium bicarbonate salt into liposomes so as to control their endosomal escape for gene therapy. Methods: A sub-200 nm nanovector was fully characterized and examined for cellular uptake, cytotoxicity, endosomal escape and gene silencing. Results: The siRNA-liposomes were internalized into cancer cells within 5 min and then released siRNAs in the cytosol prior to lysosomal degradation upon external temperature elevation. This was confirmed by confocal bioimaging and gene silencing reaching up to 90% and further demonstrated by the protein inhibition of both target genes. Conclusion: The thermoresponsiveness of ammonium bicarbonate containing liposomes enabled the rapid endosomal escape of the particles and resulted in an efficient gene silencing.
引用
收藏
页码:1421 / 1433
页数:13
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