Login Register Cart 0
General Research Article

聚乙二醇-癸二酸作为β-环糊精-聚轮烷的骨干的生物可降解聚酯：一个有前途的基因沉默载体。

卷 19, 期 4, 2019

页: [274 - 287] 页: 14

弟呕挨: 10.2174/1566523219666190808094225

价格: $65

摘要

背景：聚轮烷是一种由环糊精组成的大分子互锁组件，具有出色的包合能力和功能化能力，使其成为基因递送应用的通用载体。 目的：以聚乙二醇（PEG）和癸二酸（SA）组成的可生物降解的线性脂族聚酯轴为原料，制备基于β-环糊精（β-CD）的聚轮烷作为阳离子聚合物载体，并对其潜在的基因沉默效率进行了评估。 方法：采用溶剂酯化法合成水溶性脂肪族聚酯，并通过粘度法，GPC，FT-IR和1H NMR表征。进一步评估了合成聚酯的生物降解性和细胞毒性。因此，该水溶性聚酯通过穿线和封端反应用于聚轮烷的逐步合成。 β-CD在PEG-SA聚酯轴上的穿线在水中进行，然后使用2,4,6-三硝基苯磺酸将聚伪轮烷封端，得到聚酯基聚轮烷。对于基因传递应用，合成了阳离子聚轮烷（PRTx +）并评估了其基因加载和基因沉默效率。 结果与讨论：发现所得的新型大分子组装物可安全用于生物医学应用。此外，通过GPC和1H NMR技术表征表明，成功形成了PE-β-CD-PRTx，穿线效率为16％。此外，细胞毒性实验表明合成的聚轮烷具有生物安全性，探索了其在基因递送和其他生物医学应用中的潜力。此外，通过测量它们的ζ电位和基因沉默效率来评估PRTx +：siRNA复合物的生物学特性，发现其与商业转染剂Lipofectamine 3000相当。结论：聚乙二醇-癸二酸基β-环糊精-聚轮烷的生物降解性，良好的络合能力，接近零的ζ电势，良好的细胞毒性等多种因素的综合作用使其成为治疗应用的有希望的基因载体。

关键词: 聚酯，环糊精，聚轮烷，生物降解，siRNA，GFP，基因沉默。

« Previous
图形摘要

[1]
Pack DW, Hoffman AS, Pun S, Stayton PS. Design and development of polymers for gene delivery. Nat Rev Drug Discov 2005; 4(7): 581-93.
[http://dx.doi.org/10.1038/nrd1775] [PMID: 16052241]
[2]
Lungwitz U, Breunig M, Blunk T, Göpferich A. Polyethylenimine-based non-viral gene delivery systems. Eur J Pharm Biopharm 2005; 60(2): 247-66.
[http://dx.doi.org/10.1016/j.ejpb.2004.11.011] [PMID: 15939236]
[3]
Kodama Y, Nakamura T, Kurosaki T, et al. Biodegradable nanoparticles composed of dendrigraft poly-L-lysine for gene delivery. Eur J Pharm Biopharm 2014; 87(3): 472-9.
[http://dx.doi.org/10.1016/j.ejpb.2014.04.013] [PMID: 24813391]
[4]
Tang MX, Redemann CT, Szoka FC Jr. In vitro gene delivery by degraded polyamidoamine dendrimers. Bioconjug Chem 1996; 7(6): 703-14.
[http://dx.doi.org/10.1021/bc9600630] [PMID: 8950489]
[5]
Boussif O, Lezoualc’h F, Zanta MA, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proc Natl Acad Sci USA 1995; 92(16): 7297-301.
[http://dx.doi.org/10.1073/pnas.92.16.7297] [PMID: 7638184]
[6]
Gonzalez H, Hwang SJ, Davis ME. New class of polymers for the delivery of macromolecular therapeutics. Bioconjug Chem 1999; 10(6): 1068-74.
[http://dx.doi.org/10.1021/bc990072j] [PMID: 10563777]
[7]
Harada A. Preparation and structures of supramolecules between cyclodextrins and polymers. Coord Chem Rev 1996; 148: 115-33.
[http://dx.doi.org/10.1016/0010-8545(95)01157-9]
[8]
Harada A, Takashima Y, Yamaguchi H. Cyclodextrin-based supramolecular polymers. Chem Soc Rev 2009; 38(4): 875-82.
[http://dx.doi.org/10.1039/b705458k] [PMID: 19421567]
[9]
Badwaik V, Mondjinou Y, Kulkarni A, Liu L, Demoret A, Thompson DH. Efficient pDNA delivery using cationic 2-Hydroxypropyl-β-Cyclodextrin Pluronic-Based polyrotaxanes. Macromol Biosci 2016; 16(1): 63-73.
[http://dx.doi.org/10.1002/mabi.201500220] [PMID: 26257319]
[10]
van de Manakker F, Vermonden T, van Nostrum CF, Hennink WE. Cyclodextrin-based polymeric materials: Synthesis, properties, and pharmaceutical/biomedical applications. Biomacromolecules 2009; 10(12): 3157-75.
[http://dx.doi.org/10.1021/bm901065f] [PMID: 19921854]
[11]
Loethen S, Kim JM, Thompson DH. Biomedical applications of cyclodextrin based polyrotaxanes. J Macromol Sci Part C Polym Rev 2007; 47(3): 383-418.
[12]
Gibson HW, Liu S, Gong C, Ji Q, Joseph E. Studies of the formation of poly (ester rotaxane) s from diacid chlorides, diols, and crown ethers and their properties. Macromolecules 1997; 30(13): 3711-27.
[http://dx.doi.org/10.1021/ma961362n]
[13]
Koyama Y, Suzuki Y, Asakawa T, Kihara N, Nakazono K, Takata T. Polymer architectures assisted by dynamic covalent bonds: Synthesis and properties of boronate-functionalized polyrotaxane and graft polyrotaxane. Polym J 2012; 44: 30-7.
[14]
Lee M, Moore RB, Gibson HW. Supramolecular pseudorotaxane graft copolymer from a crown ether polyester and a complementary paraquat-terminated polystyrene guest. Macromolecules 2011; 44(15): 5987-93.
[http://dx.doi.org/10.1021/ma201241t]
[15]
Araki J, Zhao C, Ito K. Efficient production of polyrotaxanes from α-cyclodextrin and poly (ethylene glycol). Macromolecules 2005; 38(17): 7524-7.
[http://dx.doi.org/10.1021/ma050290+]
[16]
Kulkarni A, DeFrees K, Schuldt RA, et al. Multi-armed cationic cyclodextrin: Poly(ethylene glycol) polyrotaxanes as efficient gene silencing vectors. Integr Biol 2013; 5(1): 115-21.
[http://dx.doi.org/10.1039/c2ib20107k] [PMID: 23042106]
[17]
Mondjinou YA, Hyun S-H, Xiong M, Collins CJ, Thong PL, Thompson DH. Impact of Mixed β-Cyclodextrin ratios on pluronic rotaxanation efficiency and product solubility. ACS Appl Mater Interfaces 2015; 7(43): 23831-6.
[http://dx.doi.org/10.1021/acsami.5b01016] [PMID: 26502827]
[18]
Iguchi H, Uchida S, Koyama Y, Takata T. Polyester-containing α-cyclodextrin-based polyrotaxane: Synthesis by living ring-opening polymerization, polypseudorotaxanation, and end capping using nitrile N-oxide. ACS Macro Lett 2013; 2(6): 527-30.
[http://dx.doi.org/10.1021/mz4002518]
[19]
Wang P-J, Wang J, Ye L, Zhang A-Y, Feng Z-G. Synthesis and characterization of polyrotaxanes comprising α-cyclodextrins and poly (ε-caprolactone) end-capped with poly (N-isopropylacrylamide)s. Polymer 2012; 53(12): 2361-8.
[http://dx.doi.org/10.1016/j.polymer.2012.03.060]
[20]
Wang PJ, Ye L, Zhang AY, Feng ZG. Synthesis and characterization of polyrotaxanes comprising α‐cyclodextrins and poly (ε‐caprolactone) end‐capped with poly (butyl methacrylate) s. Polym Int 2014; 63(6): 1025-34.
[http://dx.doi.org/10.1002/pi.4605]
[21]
Shin KM, Dong T, He Y, et al. Inclusion complex formation between α-cyclodextrin and biodegradable aliphatic polyesters. Macromol Biosci 2004; 4(12): 1075-83.
[http://dx.doi.org/10.1002/mabi.200400118] [PMID: 15586392]
[22]
Shin KM, Dong T, He Y, Inoue Y. Morphological change of poly (ε‐caprolactone) with a wide range of molecular weight via formation of inclusion complex with α‐cyclodextrin. J Polym Sci, B, Polym Phys 2005; 43(12): 1433-40.
[http://dx.doi.org/10.1002/polb.20449]
[23]
Ulery BD, Nair LS, Laurencin CT. Biomedical applications of biodegradable polymers. J Polym Sci, B, Polym Phys 2011; 49(12): 832-64.
[http://dx.doi.org/10.1002/polb.22259] [PMID: 21769165]
[24]
Ji Y, Liu X, Huang M, et al. Development of self-assembled multi-arm polyrotaxanes nanocarriers for systemic plasmid delivery in vivo. Biomaterials 2019; 192: 416-28.
[http://dx.doi.org/10.1016/j.biomaterials.2018.11.027] [PMID: 30500723]
[25]
Ahn B, Kim S, Kim Y, Yang J. Synthesis and characterization of the biodegradable copolymers from succinic acid and adipic acid with 1, 4‐butanediol. J Appl Polym Sci 2001; 82(11): 2808-26.
[http://dx.doi.org/10.1002/app.2135]
[26]
Brioude MdM. Guimarães DH, Fiúza RdP, Prado LASdA, Boaventura JS, José NM. Synthesis and characterization of aliphatic polyesters from glycerol, by-product of biodiesel production, and adipic acid. Mater Res 2007; 10(4): 335-9.
[http://dx.doi.org/10.1590/S1516-14392007000400003]
[27]
Nikolic MS, Djonlagic J. Synthesis and characterization of biodegradable poly (butylene succinate-co-butylene adipate) s. Polym Degrad Stabil 2001; 74(2): 263-70.
[http://dx.doi.org/10.1016/S0141-3910(01)00156-2]
[28]
Tserki V, Matzinos P, Pavlidou E, Vachliotis D, Panayiotou C. Biodegradable aliphatic polyesters. Part I. Properties and biodegradation of poly (butylene succinate-co-butylene adipate). Polym Degrad Stabil 2006; 91(2): 367-76.
[http://dx.doi.org/10.1016/j.polymdegradstab.2005.04.035]
[29]
Anastas PT, Zimmerman JB. Peer reviewed: Design through the 12 principles of green engineering. Environ Sci Technol 2003; 37(5): 94A-101A.
[30]
Nair LS, Laurencin CT. Biodegradable polymers as biomaterials. Prog Polym Sci 2007; 32(8): 762-98.
[http://dx.doi.org/10.1016/j.progpolymsci.2007.05.017]
[31]
Li JJ, Zhao F, Li J. Polyrotaxanes for applications in life science and biotechnology. Appl Microbiol Biotechnol 2011; 90(2): 427-43.
[http://dx.doi.org/10.1007/s00253-010-3037-x] [PMID: 21360153]
[32]
Yamada Y, Nomura T, Harashima H, Yamashita A, Katoono R, Yui N. Intranuclear DNA release is a determinant of transfection activity for a non-viral vector: Biocleavable polyrotaxane as a supramolecularly dissociative condenser for efficient intranuclear DNA release. Biol Pharm Bull 2010; 33(7): 1218-22.
[http://dx.doi.org/10.1248/bpb.33.1218] [PMID: 20606316]
[33]
Ooya T, Choi HS, Yamashita A, et al. Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced gene delivery. J Am Chem Soc 2006; 128(12): 3852-3.
[http://dx.doi.org/10.1021/ja055868+] [PMID: 16551060]
[34]
Yamashita A, Kanda D, Katoono R, et al. Supramolecular control of polyplex dissociation and cell transfection: Efficacy of amino groups and threading cyclodextrins in biocleavable polyrotaxanes. J Control Release 2008; 131(2): 137-44.
[http://dx.doi.org/10.1016/j.jconrel.2008.07.011] [PMID: 18700157]
[35]
Kulkarni A, DeFrees K, Schuldt RA, et al. Cationic α-cyclodextrin: Poly(ethylene glycol) polyrotaxanes for siRNA delivery. Mol Pharm 2013; 10(4): 1299-305.
[http://dx.doi.org/10.1021/mp300449t] [PMID: 23398604]
[36]
Badwaik VD, Aicart E, Mondjinou YA, Johnson MA, Bowman VD, Thompson DH. Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors. Biomaterials 2016; 84: 86-98.
[http://dx.doi.org/10.1016/j.biomaterials.2015.11.032] [PMID: 26826298]
[37]
Dandekar P, Jain R, Keil M, et al. Enhanced uptake and siRNA-mediated knockdown of a biologically relevant gene using cyclodextrin polyrotaxane. J Mater Chem B Mater Biol Med 2015; 3(13): 2590-8.
[http://dx.doi.org/10.1039/C4TB01821D]
[38]
Sanadhya SG, Oswal S, Parmar KC. Synthesis and characterization of aliphatic-aromatic polyesters using interfacial polycondensation technique. J Chem Pharm Res 2014; 6: 705-14.
[39]
Collins CJ, McCauliff LA, Hyun S-H, et al. Synthesis, characterization, and evaluation of pluronic-based β-cyclodextrin polyrotaxanes for mobilization of accumulated cholesterol from Niemann-Pick type C fibroblasts. Biochemistry 2013; 52(19): 3242-53.
[http://dx.doi.org/10.1021/bi3010889] [PMID: 23560535]
[40]
Mann A, Richa R, Ganguli M. DNA condensation by poly-L-lysine at the single molecule level: Role of DNA concentration and polymer length. J Control Release 2008; 125(3): 252-62.
[http://dx.doi.org/10.1016/j.jconrel.2007.10.019] [PMID: 18068848]
[41]
Pawlak JA, Lemper AL, Pattison VA. Solution polycondensation method 1977. Available from: http://shodhganga.inflibnet.ac.in/jspui/bitstream/10603/145620/14/11_chapter%201.pdf
[42]
Zhou X-M. Synthesis and characterization of polyester copolymers based on poly (butylene succinate) and poly (ethylene glycol). Mater Sci Eng C 2012; 32(8): 2459-63.
[http://dx.doi.org/10.1016/j.msec.2012.07.025]
[43]
Zhao T, Beckham HW. Direct synthesis of cyclodextrin-rotaxanated poly (ethylene glycol) s and their self-diffusion behavior in dilute solution. Macromolecules 2003; 36(26): 9859-65.
[http://dx.doi.org/10.1021/ma035513f]
[44]
Mayumi K, Ito K, Kato K. Polyrotaxane and slide-ring materials. Royal Society of Chemistry 2015.
[http://dx.doi.org/10.1039/9781782622284]
[45]
Lyu S, Untereker D. Degradability of polymers for implantable biomedical devices. Int J Mol Sci 2009; 10(9): 4033-65.
[http://dx.doi.org/10.3390/ijms10094033] [PMID: 19865531]
[46]
Kim J, Lee K-W, Hefferan TE, Currier BL, Yaszemski MJ, Lu L. Synthesis and evaluation of novel biodegradable hydrogels based on poly(ethylene glycol) and sebacic acid as tissue engineering scaffolds. Biomacromolecules 2008; 9(1): 149-57.
[http://dx.doi.org/10.1021/bm700924n] [PMID: 18072747]
[47]
Liu G, Li Y, Yang L, et al. Cytotoxicity study of polyethylene glycol derivatives. RSC Advances 2017; 7(30): 18252-9.
[http://dx.doi.org/10.1039/C7RA00861A]
[48]
Kunath K, von Harpe A, Fischer D, et al. Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: Comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine. J Control Release 2003; 89(1): 113-25.
[http://dx.doi.org/10.1016/S0168-3659(03)00076-2] [PMID: 12695067]
[49]
Okon EU, Hammed G, El Wafa PA, Abraham O, Case N, Henry E. In-vitro cytotoxicity of Polyethyleneimine on HeLa and vero cells. IJIAS 2014; 5(3): 192.
[50]
Yang C, Wang X, Li H, Tan E, Lim CT, Li J. Cationic polyrotaxanes as gene carriers: Physicochemical properties and real-time observation of DNA complexation, and gene transfection in cancer cells. J Phys Chem B 2009; 113(22): 7903-11.
[http://dx.doi.org/10.1021/jp901302f] [PMID: 19422177]
[51]
Yang C, Wang X, Li H, Goh SH, Li J. Synthesis and characterization of polyrotaxanes consisting of cationic α-cyclodextrins threaded on poly[(ethylene oxide)-ran-(propylene oxide)] as gene carriers. Biomacromolecules 2007; 8(11): 3365-74.
[http://dx.doi.org/10.1021/bm700472t] [PMID: 17929967]

Rights & Permissions Print Cite
Article Metrics
28
4
1
© 2024 Bentham Science Publishers | Privacy Policy