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CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL escape AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA

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Chinese Journal of Polymer Science 2013年第6期31卷 912-923页

作者： Ruo-gu Qi Su-hong Wu Yu Wang Jie Chen Zhi-gang Xie Yu-bin Huang 景遐斌 State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences

To further enhance the transfection efficiency of a micelleplex system based on monomethoxy poly（ethylene glycol）-block-poly（e-caprolactone）-block-poly（L-lysine）（MPEG-b-PCL-b-PLL）, cholesterol （Chol） moieties are attached to the e-termini of PLL segments to obtain MPEG-b-PCL-b-PLL/Chol. The structure and morphology of the copolymer are studied by IH-NMR, TEM and DLS （dynamic light scattering）. The cytotoxicity, cell uptake, endosomal release and mRNA knockdown are studied by MTT （3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide） assay, flow cytometry, CLSM （confocal laser scanning microscopy） and RT-PCR （real-time polymerase chain reaction）. The results show that compared to their precursor MPEG-b-PCL-b-PLL, the cholesterol-grafted copolymer shows significantly lower toxicity, more rapid cellular endocytosis and endosome escape, and consequently displays enhanced siRNA transfection efficiency even at a lower N/P ratio. These improvements are ascribed to enhanced interaction of the cholesterol moieties with both cellular membrane and endosomal membrane. Moreover, effect of the PLL block length is examined. The final conclusion is that long enough PLL segments and incorporation of proper fraction of cholesterol onto the PLL segments benefit the enhancement of siRNA transfection efficiency.

关键词： Amphiphilic copolymer Cholesterol endosome escape Micelleplex siRNA delivery.

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siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment

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Nano Research 2022年第10期15卷 9160-9168页

作者： Chanchan Yu Kun Li Lin Xu Bo Li Chunhui Li Shuai Guo Ziyue Li Yuquan Zhang Abid Hussain Hong Tan Mengyu Zhang Yongxiang Zhao Yuanyu Huang Xing-Jie Liang School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical Technology(Institute of Engineering Medicine)Key Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China National Center for International Research of Biological Targeting Diagnosis and Therapy Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy ResearchGuangxi Medical UniversityNanning 530021China

Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug ***,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the ***,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane *** to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.

关键词： coordination chemistry nuclei acid lanthanide nanomaterials small interfering RNA(siRNA)delivery endosome escape

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Lipid carriers for mRNA delivery

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药学学报:英文版 2023年第10期13卷 4105-4126页

作者： Wanting Zhang Yuxin Jiang Yonglong He Hamza Boucetta Jun Wu Zhongjian Chen Wei He Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Department of Geriatric Cardiology Jiangsu Provincial Key Laboratory of GeriatricsThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Messenger RNA(mRNA)is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases,including viral infection and ***,mRNA-based vaccines,as a new type of vaccine,have played a leading role in fighting against the current global pandemic of ***,the inherent drawbacks,including large size,negative charge,and instability,hinder its use as a therapeutic *** carriers are distinguishable and promising vehicles for mRNA delivery,owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired ***,we first summarized the structure and properties of different lipid carriers,such as liposomes,liposome-like nanoparticles,solid lipid nanoparticles,lipid-polymer hybrid nanoparticles,nanoemulsions,exosomes and lipoprotein particles,and their applications in delivering ***,the development of lipid-based formulations as vaccine delivery systems was discussed and *** advancements in the mRNA vaccine of COVID-19 were ***,we described our future vision and perspectives in this field.

关键词： mRNA Lipid carriers Drug delivery endosome escape Nanoparticles Encapsulation efficiency Vaccine COVID-19

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