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树形分子在siRNA递送载体中的应用

蔡龚莉, 陈裕, 林舒婷, 朱丹丹, 董怡文, 李宁, 刘潇璇

蔡龚莉, 陈裕, 林舒婷, 朱丹丹, 董怡文, 李宁, 刘潇璇. 树形分子在siRNA递送载体中的应用[J]. 中国药科大学学报, 2019, 50(3): 274-288. DOI: 10.11665/j.issn.1000-5048.20190303
引用本文: 蔡龚莉, 陈裕, 林舒婷, 朱丹丹, 董怡文, 李宁, 刘潇璇. 树形分子在siRNA递送载体中的应用[J]. 中国药科大学学报, 2019, 50(3): 274-288. DOI: 10.11665/j.issn.1000-5048.20190303
CAI Gongli, CHEN Yu, LIN Shuting, ZHU Dandan, DONG Yiwen, LI Ning, LIU Xiaoxuan. Application of dendrimer-based siRNA delivery systems[J]. Journal of China Pharmaceutical University, 2019, 50(3): 274-288. DOI: 10.11665/j.issn.1000-5048.20190303
Citation: CAI Gongli, CHEN Yu, LIN Shuting, ZHU Dandan, DONG Yiwen, LI Ning, LIU Xiaoxuan. Application of dendrimer-based siRNA delivery systems[J]. Journal of China Pharmaceutical University, 2019, 50(3): 274-288. DOI: 10.11665/j.issn.1000-5048.20190303

树形分子在siRNA递送载体中的应用

基金项目: 国家自然科学基金资助项目(No.51773227,No.81701815,No.51703245);江苏省自然科学基金资助项目(No.BK20170735,No.BK20170733);中组部“千人计划”青年资助项目;江苏省“高层次创新创业人才引进计划”资助项目;中国药科大学“双一流”建设科技创新团队资助项目(No.CPU2018GF05);中国药科大学天然药物活性组分与药效国家重点实验室资助项目(No.SKLNMZZRC201804);中国高校基本科研业务费资助项目(No.2632019ZD09)

Application of dendrimer-based siRNA delivery systems

  • 摘要: 基于小干扰核酸分子(siRNA)的RNA干扰技术作为极具潜力的治疗策略吸引了越来越多的学术界和工业界的关注,如何实现siRNA的临床转化日渐成为生物医药领域的研究热点。然而,转化成功与否很大程度上依赖于安全高效的siRNA递送系统。树形分子作为一种新型的大分子,具有精确可控的化学结构、可供修饰的末端基团以及纳米尺寸等独特的物理化学性质,广泛应用于siRNA的递送。本文归纳和总结了不同种类的树形分子在siRNA递送领域的研究进展,为后续树形分子用于siRNA递送的研究提供思路。
    Abstract: Small interfering RNA-based RNA interference(RNAi)is an emerging treatment which has attracted more and more attention from both academia and industry. Studies on clinical translation of siRNA are popular in biomedical field, where safe and efficient carriers are necessary. As novel drug/gene vectors, dendrimers are widely used in siRNA delivery due to their unique and precise structure, multiple terminal groups and nano-sized chemophysical properties. Here, we present an overall view of current studies on dendrimer-based siRNA delivery systems, with the aim to provide an understanding of future siRNA therapeutics which could be used in clinic.
  • [1] Fire A,Xu S,Montgomery MK,et al.Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans[J].Nature,1998,391(6669):806-811.
    [2] Hannon GJ.RNA interference[J].Nature,2002,418(6894):244-251.
    [3] Setten RL,Rossi JJ,Han SP.The current state and future directions of RNAi-based therapeutics[J].Nat Rev Drug Discov,2019.DOI: 10.1038/s41573-019-0017-4.
    [4] Yin H,Kanasty RL,Eltoukhy AA,et al.Non-viral vectors for gene-based therapy[J].Nat Rev Genet,2014,15(8):541-555.
    [5] Mintzer MA,Grinstaff MW.Biomedical applications of dendrimers:a tutorial[J].Chem Soc Rev,2011,40(1):173-190.
    [6] Tomalia DA.Birth of a new macromolecular architecture:dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry[J].Prog Polym Sci,2005,30(3/4):294-324.
    [7] Biswas S,Torchilin VP.Dendrimers for siRNA Delivery[J].Pharmaceuticals,2013,6(2):161-183.
    [8] Tomalia DA,Baker H,Dewald J,et al.A new class of polymers:starburst-dendritic macromolecules[J].Polym J,1985,17(1):117-132.
    [9] Liu X,Rocchi P,Peng L.Dendrimers as non-viral vectors for siRNA delivery[J].New J Chem,2012,36:256-263.
    [10] Tang MX,Redemann CT,Jr SF.In vitro gene delivery by degraded polyamidoamine dendrimers[J].Bioconjug Chem,1996,7(6):703-714.
    [11] Kang H,DeLong R,Fisher MH,et al.Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides[J].Pharm Res,2005,22(12):2099-2106.
    [12] Zhou J,Wu J,Hafdi N,et al.PAMAM dendrimers for efficient siRNA delivery and potent gene silencing[J].Chem Commun,2006,22:2362-2364.
    [13] Liu X,Rocchi P,Qu F,et al.PAMAM dendrimers mediate siRNA delivery to target Hsp27 and produce potent antiproliferative effects on prostate cancer cells[J].ChemMedChem,2009,4(8):1302-1310.
    [14] Zhou J,Neff CP,Liu X,et al.Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice[J].Mol Ther,2011,19(12):2228-2238.
    [15] Ma J,Kala S,Yung S,et al.Blocking sternness and metastatic properties of ovarian cancer cells by targeting p70(S6K)with dendrimer nanovector-based siRNA delivery[J].Mol Ther,2018,26(1):70-83.
    [16] Reebye V,Saetrom P,Mintz PJ,et al.Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo[J].Hepatology,2014,59(1):216-227.
    [17] Cui Q,Yang S,Ye P,et al.Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis[J].Nat Commun,2016,7:10637-10652.
    [18] Tang Y,Li YB,Wang B,et al.Efficient in vitro siRNA delivery and intramuscular gene silencing using PEG-modified PAMAM dendrimers[J].Mol Pharmaceutics,2012,9(6):1812-1821.
    [19] Ma Y,Sha M,Cheng S,et al.Construction of hyaluronic tetrasaccharide clusters modified polyamidoamine siRNA delivery system[J].Nanomaterials,2018,8(6):433-446.
    [20] Liu X,Liu C,Chen C,et al.Targeted delivery of dicer-substrate siRNAs using a dual targeting peptide decorated dendrimer deli-very system[J].Nanomedicine,2014,10(8):1627-1636.
    [21] Liu C,Liu X,Rocchi P,et al.Arginine-terminated generation 4 PAMAM dendrimer as an effective nanovector for functional siRNA delivery in vitro and in vivo[J].Bioconjug Chem,2014,25(3):521-532.
    [22] Chang H,Zhang YM,Li L,et al.Efficient delivery of small interfering RNA into cancer cells using dodecylated dendrimers[J].J Mater Chem B,2015,3:8197-8202.
    [23] Biswas S, Deshpande PP, Navarro G, et al. Lipid modified triblock PAMAM-based nanocarriers for siRNA drug co-delivery[J].Biomaterials,2013,34(4):1289-1301.
    [24] He B,Wang Y,Shao N,et al.Polymers modified with double-tailed fluorous compounds for efficient DNA and siRNA delivery[J].Acta Biomater,2015,22:111-119.
    [25] Wang M,Cheng Y.Structure-activity relationships of fluorinated dendrimers in DNA and siRNA delivery[J].Acta Biomater,2016,46:204-210.
    [26] Buhleier E,Wehner W,Voegtle F.“Cascade”-and “nonskid-chain-like” syntheses of molecular cavity topplogies[J].Chem Informationsdienst,1978,9(25):155-158.
    [27] de Brabander-van den Berg E,Meijer E.Poly(propylene imine)dendrimers:large-scale synthesis by hetereogeneously catalyzed hydrogenations[J].Angew Chem Int Ed,1993,32(9):1308-1311.
    [28] Wörner C,Mülhaupt R.Polynitrile- and polyamin-functional poly(trimethylene imine)dendrimers[J].Angew Chem Int Ed,1993,32(9):1306-1308.
    [29] Tietze S,Schau I,Michen S,et al.A poly(propyleneimine)dendrimer-based polyplex-system for single-chain antibody-mediated targeted delivery and cellular uptake of siRNA[J].Small,2017,13(27):1700072-1700088.
    [30] Schumann C,Chan S,Khalimonchuk O,et al.Mechanistic nanotherapeutic approach based on siRNA-mediated DJ-1 protein suppression for platinum-resistant ovarian cancer[J].Mol Pharmaceutics,2016,13(6):2070-2083.
    [31] Taratula O,Garbuzenko OB,Kirkpatrick P,et al.Surface-engineered targeted PPI dendrimer for efficient intracellular and intratumoral siRNA delivery[J].J Control Release,2009,140(3):284-293.
    [32] Omidi Y,Hollins AJ,Drayton RM,et al.Polypropylenimine dendrimer-induced gene expression changes:the effect of complexation with DNA,dendrimer generation and cell type[J].J Drug Target,2005,13(7):431-443.
    [33] Santos SS,Gonzaga RV,Silva JV,et al.Peptide dendrimers:drug/gene delivery and other approaches[J].Can J Chem,2017,95(9):907-916.
    [34] Tam JP,Spetzler JC.Synthesis and application of peptide dendrimers as protein mimetics[J].Curr Protoc Protein Sci,2001.doi: 10.1002/0471140864.ps1805S17.
    [35] Inoue Y,Kurihara R,Tsuchida A,et al.Efficient delivery of siRNA using dendritic poly(L-lysine)for loss-of-function analysis[J].J Control Release,2008,126(1):59-66.
    [36] Baigude H,Su J,McCarroll J,et al.In vivo delivery of RNAi by reducible interfering nanoparticles(iNOPs)[J].ACS Med Chem Lett,2013,4(8):720-723.
    [37] Cai X,Zhu H,Zhang Y,et al.Highly efficient and safe delivery of VEGF siRNA by bioreducible fluorinated peptide dendrimers for cancer therapy[J].ACS Appl Mater Interfaces,2017,9(11):9402-9415.
    [38] Haag R,Sunder A,Stumbe JF.An approach to glycerol dendrimers and pseudo-dendritic polyglycerols[J].J Am Chem Soc,2000,122(12):2954-2955.
    [39] Fischer W,Calderon M,Schulz A,et al.Dendritic polyglycerols with oligoamine shells show low toxicity and high siRNA transfection efficiency in vitro[J].Bioconjug Chem,2010,21(10):1744-1752.
    [40] Mehrabadi FS,Hirsch O,Zeisig R,et al.Structure-activity relationship study of dendritic polyglycerolamines for efficient siRNA transfection[J].RSC Adv,2015,5:78760-78770.
    [41] Zeng H,Schlesener C,Cromwell O,et al.Amino acid-functionalized dendritic polyglycerol for safe and effective siRNA delivery[J].Biomacromolecules,2015,16(12):3869-3877.
    [42] Wen Y, Guo Z, Du Z, et al. Serum tolerance and endosomal escape capacity of histidine-modified pDNA-loaded complexes based on polyamidoamine dendrimer derivatives[J].Biomaterials,2012,33(32):8111-8121.
    [43] Mehrabadi FS,Zeng HX,Johnson M,et al.Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection[J].Beilstein J Org Chem,2015,11:763-772.
    [44] Krska SW,Seyferth D.Synthesis of water-soluble carbosilane dendrimers[J].J Am Chem Soc,1998,120:3604-3612.
    [45] Weber N,Ortega P,Clemente MI,et al.Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes[J].J Control Release,2008,132(1):55-64.
    [46] Pedziwiatr-Werbicka E,Fuentes E,Dzmitruk V,et al.Novel ‘Si-C’ carbosilane dendrimers as carriers for anti-HIV nucleic acids:studies on complexation and interaction with blood cells[J].Colloids Surf B Biointerfaces,2013,109:183-189.
    [47] de Las Cuevas N,Garcia-Gallego S,Rasines B,et al.In vitro studies of water-stable cationic carbosilane dendrimers as delivery vehicles for gene therapy against HIV and hepatocarcinoma[J].Curr Med Chem,2012,19(29):5052-5061.
    [48] Fuentes-Paniagua E,Hernandez-Ros JM,Sanchez-Milla M,et al.Carbosilane cationic dendrimers synthesized by thiol-ene click chemistry and their use as antibacterial agents[J].RSC Adv,2014,4:1256-1265.
    [49] Herma R,Wrobel D,Liegertova M,et al.Carbosilane dendrimers with phosphonium terminal groups are low toxic non-viral transfection vectors for siRNA cell delivery[J].Int J Pharm,2019,562:51-65.
    [50] Chen HT,Neerman MF,Parrish AR,et al.Cytotoxicity,hemolysis,and acute in vivo toxicity of dendrimers based on melamine,candidate vehicles for drug delivery[J].J Am Chem Soc,2004,126(32):10044-10048.
    [51] Merkel OM,Mintzer MA,Librizzi D,et al.Triazine dendrimers as nonviral vectors for in vitro and in vivo RNAi:the effects of peripheral groups and core structure on biological activity[J].Mol Pharmaceutics,2010,7(4):969-983.
    [52] Pavan GM,Mintzer MA,Simanek EE,et al.Computational insights into the interactions between DNA and siRNA with “rigid” and “flexible” triazine dendrimers[J].Biomacromolecules,2010,11(3):721-730.
    [53] Yu T,Liu X,Bolcato-Bellemin AL,et al.An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo[J].Angew Chem Int Ed,2012,51(34):8478-8484.
    [54] Chen C,Posocco P,Liu X,et al.Mastering dendrimer self-assembly for efficient siRNA delivery:from conceptual design to in vivo efficient gene silencing[J].Small,2016,12(27):3667-3676.
    [55] Liu X,Zhou J,Yu T,et al.Adaptive amphiphilic dendrimer-based nanoassemblies as robust and versatile siRNA delivery systems[J].Angew Chem Int Ed,2014,53(44):11822-11827.
    [56] Liu X, Liu C, Zhou J, et al. Promoting siRNA delivery via enhanced cellular uptake using an arginine-decorated amphiphilic dendrimer[J].Nanoscale,2015,7(9):3867-3875.
    [57] Dong Y,Yu T,Ding L,et al.A dual targeting dendrimer-mediated siRNA delivery system for effective gene silencing in cancer therapy[J].J Am Chem Soc,2018,140(47):16264-16274.
    [58] Liu X,Wang Y,Chen C,et al.A fluorinated bola-amphiphilic dendrimer for on-demand delivery of siRNA,via specific response to reactive oxygen species[J].Adv Funct Mater,2016,26(47):8594-8603.
    [59] Li X,Sun AN,Liu YJ,et al.Amphiphilic dendrimer engineered nanocarrier systems for co-delivery of siRNA and paclitaxel to matrix metalloproteinase-rich tumors for synergistic therapy[J].Npg Asia Mater,2018,10:238-254.
    [60] Malhotra S,Bauer H,Tschiche A,et al.Glycine-terminated dendritic amphiphiles for nonviral gene delivery[J].Biomacromolecules,2012,13(10):3087-3098.
    [61] Tschiche A,Staedtler AM,Malhotra S,et al.Polyglycerol-based amphiphilic dendrons as potential siRNA carriers for in vivo applications[J].J Mater Chem B,2014,2:2153-2167.
    [62] Tschiche A, Thota BN, Neumann F, et al. Crosslinked redox-responsive micelles based on lipoic acid-derived amphiphiles for enhanced siRNA delivery[J].Macromol Biosci,2016,16(6):811-823.
    [63] Sanchez-Nieves J,Fransen P,Pulido D,et al.Amphiphilic cationic carbosilane-PEG dendrimers:synthesis and applications in gene therapy[J].Eur J Med Chem,2014,76:43-52.
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  • 刊出日期:  2019-06-24

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