利用高分子多基元协同效应增强脂质体稳定性的研究

田显城; 董原辰; 孙亚伟; 刘冬生

doi:10.11777/j.issn1000-3304.2022.22305

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利用高分子多基元协同效应增强脂质体稳定性的研究

研究论文 | 更新时间：2024-01-18

- 利用高分子多基元协同效应增强脂质体稳定性的研究
  增强出版
- Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units
- 高分子学报 2023年54卷第5期页码：675-686
- 作者机构：
  
  1.稀土新材料教育部工程研究中心
  2.生命有机磷化学及化学生物学教育部重点实验室清华大学化学系北京 100084
  3.中国科学院化学研究所北京 100190
  4.中国石油大学（华东）化学工程学院青岛 258000
- 作者简介：
  
  E-mail: liudongsheng@tsinghua.edu.cn
- 基金信息：
  
  中国科学院化学研究所人才基金(基金号 C220200701);国家自然科学基金(基金号 ┣21821001;21890730);20890731┫;国家重点研发计划(2020YFC200201)
- DOI：10.11777/j.issn1000-3304.2022.22305
  中图分类号：
- 纸质出版日期：2023-05-20，
  
  网络出版日期：2022-11-24，
  
  收稿日期：2022-09-08，
  
  录用日期：2022-11-01
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田显城,董原辰,孙亚伟等.利用高分子多基元协同效应增强脂质体稳定性的研究[J].高分子学报,2023,54(05):675-686.

Tian Xian-cheng,Dong Yuan-chen,Sun Ya-wei,et al.Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units[J].ACTA POLYMERICA SINICA,2023,54(05):675-686.
田显城,董原辰,孙亚伟等.利用高分子多基元协同效应增强脂质体稳定性的研究[J].高分子学报,2023,54(05):675-686. DOI： 10.11777/j.issn1000-3304.2022.22305.

Tian Xian-cheng,Dong Yuan-chen,Sun Ya-wei,et al.Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units[J].ACTA POLYMERICA SINICA,2023,54(05):675-686. DOI： 10.11777/j.issn1000-3304.2022.22305.

摘要

通过合成接枝胆固醇的壳聚糖水溶性高分子，并利用所接枝胆固醇的插膜能力，诱导高分子贴附于脂质体表面，形成高分子-脂质体复合物. 研究发现，壳聚糖水溶性高分子可以起到屏蔽膜表面电荷的作用，同时该体系利用高分子链上多位点修饰的疏水基团与磷脂分子之间的疏水作用和高分子多基元之间共价连接的协同效应，增强了脂质体的抗融合及抗表面活性剂能力. 该复合策略制备过程简便快捷，在体外实验中已展现出良好的稳定性，在长循环药物递送方面具有潜在的应用.

Abstract

We synthesized a water soluble glycol chitosan polymer grafted with cholesterol through substitution reaction

and the polymer was applied to form a polymer-liposome complex (PLC). According to dynamic light scattering (DLS) and transmission electron microscope (TEM) characterization

the diameter of the PLC was about 100 nm and the morphology was similar to the plain liposome. The cholesterol group can induce the polymer backbone to attach to the surface of the liposome membrane and the integration cability of the glycol chitosan-cholesterol (GCC) was characterized by laser confocal scanning microscope (LCSM). The zeta potential of the liposome containing negative charged phospholipid was -23.2 mV. With integration of the glycol chitosan-cholesterol

the zeta potential significantly increased to -1.78 mV

which indicated that the attached water-soluble polymer can shield the surface charge of the membrane. By encapsulating fluorescent molecules in the liposome or mixing fluorescent phospholipid during the lipid preparation process

fluorescence resonance energy transfer (FRET) experiment was introduced to test the stability of the PLC. Charge-induced liposome fusion occurred by adding positively charged ions or liposome into negatively charged liposome solution. The PLC has shown the ability to resist the fusion process which can keep the integrity and monodispersity of the liposome. However

the plain liposome was observed in aggregates visible to the naked eyes after adding hetero-charged ions in several minutes. The FRET variation results indicated that the addition of the GCC can slow down the hetero-charged liposome fusion process. In addition

the PLC can also protect against the liposome leakage induced by surfactant

which resulted from synergistic effect of polymer multiple-units. Incubated with 20% FBS under 37 ℃

the PLC showed well stability in 3 days

while the PDI and the size of the plain liposome were increased obviously during incubation. The preparation process of this polymer-liposome complex strategy is simple and fast

and it has shown good stability in

in vitro

experiments. This system has potential applications in long circulation drug delivery.

关键词

脂质体稳定性高分子复合物

Keywords

LiposomeStabilityPolymerComplex

references

Fenton O. S.; Olafson K. N.; Pillai P. S.; Mitchell M. J.; Langer R. Advances in biomaterials for drug delivery. Adv. Mater., 2018, 30(29), 1705328. doi:10.1002/adma.201705328http://dx.doi.org/10.1002/adma.201705328

Yang B.; Zhang X. D.; Li J.; Tian J.; Wu Y. P.; Yu F. X.; Wang R. B.; Wang H.; Zhang D. W.; Liu Y.; Zhou L.; Li Z. T. In situ loading and delivery of short single- and double-stranded DNA by supramolecular organic frameworks. CCS Chem., 2019, 1(2), 156-165. doi:10.31635/ccschem.019.20180011http://dx.doi.org/10.31635/ccschem.019.20180011

Yu N.; Zhang Y. F.; Li J. Y.; Gu W. X.; Yue S. J.; Li B.; Meng F. H.; Sun H. L.; Haag R. N.; Yuan J. D.; Zhong Z. Y. Daratumumab immunopolymersome-enabled safe and CD38-targeted chemotherapy and depletion of multiple myeloma. Adv. Mater., 2021, 33(39), 2007787. doi:10.1002/adma.202007787http://dx.doi.org/10.1002/adma.202007787

Zhang J.; Wang X. X.; Cheng L.; Yuan J. D.; Zhong Z. Y. Sp94 peptide mediating highly specific and efficacious delivery of polymersomal doxorubicin hydrochloride to hepatocellular carcinoma in vivo. Colloids Surf. B Biointerfaces, 2021, 197, 111399. doi:10.1016/j.colsurfb.2020.111399http://dx.doi.org/10.1016/j.colsurfb.2020.111399

姚陈志, 汪枭睿, 胡进明, 刘世勇. 高分子囊泡渗透性与微结构协同调控. 高分子学报, 2019, 50(6), 553-566. doi:10.11777/j.issn1000-3304.2019.190031http://dx.doi.org/10.11777/j.issn1000-3304.2019.190031

Chiang Y. T.; Cheng Y. T.; Lu C. Y.; Yen Y. W.; Yu L. Y.; Yu K. S.; Lyu S. Y.; Yang C. Y.; Lo C. L. Polymer-liposome complexes with a functional hydrogen-bond cross-linker for preventing protein adsorption and improving tumor accumulation. Chem. Mater., 2013, 25(21), 4364-4372. doi:10.1021/cm402614khttp://dx.doi.org/10.1021/cm402614k

Fan Y. C.; Marioli M.; Zhang K. Analytical characterization of liposomes and other lipid nanoparticles for drug delivery. J. Pharm. Biomed. Anal., 2021, 192, 113642. doi:10.1016/j.jpba.2020.113642http://dx.doi.org/10.1016/j.jpba.2020.113642

Gref R.; Minamitake Y.; Peracchia M. T.; Trubetskoy V.; Torchilin V.; Langer R. Biodegradable long-circulating polymeric nanospheres. Science, 1994, 263(5153), 1600-1603. doi:10.1126/science.8128245http://dx.doi.org/10.1126/science.8128245

Chan C. L.; Majzoub R. N.; Shirazi R. S.; Ewert K. K.; Chen Y. J.; Liang K. S.; Safinya C. R. Endosomal escape and transfection efficiency of PEGylated cationic liposome-DNA complexes prepared with an acid-labile peg-lipid. Biomaterials, 2012, 33(19), 4928-4935. doi:10.1016/j.biomaterials.2012.03.038http://dx.doi.org/10.1016/j.biomaterials.2012.03.038

Chan J. M.; Zhang L. F.; Yuet K. P.; Liao G.; Rhee J. W.; Langer R.; Farokhzad O. C. PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery. Biomaterials, 2009, 30(8), 1627-1634. doi:10.1016/j.biomaterials.2008.12.013http://dx.doi.org/10.1016/j.biomaterials.2008.12.013

Kang S. Y.; Seong B. S.; Han Y. S.; Jung H. T. Self-organization of amphiphilic polymer in vesicle bilayers composed of surfactant mixtures. Biomacromolecules, 2003, 4(2), 360-365. doi:10.1021/bm025704ahttp://dx.doi.org/10.1021/bm025704a

Deygen I. M.; Seidl C.; Kolmel D. K.; Bednarek C.; Heissler S.; Kudryashova E. V.; Brase S.; Schepers U. Novel prodrug of doxorubicin modified by stearoylspermine encapsulated into PEG-chitosan-stabilized liposomes. Langmuir, 2016, 32(42), 10861-10869. doi:10.1021/acs.langmuir.6b01023http://dx.doi.org/10.1021/acs.langmuir.6b01023

Ishihara K.; Tsujino R.; Mika H.; Toyoda N.; Iwasaki Y. Stabilized liposomes with phospholipid polymers and their interactions with blood cells. Colloids Surf. B Biointerfaces, 2002, 25(4), 325-333. doi:10.1016/s0927-7765(02)00006-1http://dx.doi.org/10.1016/s0927-7765(02)00006-1

Meland H. G.; Rov-Johnsen A.; Smistad G.; Hiorth M. Studies on surface coating of phospholipid vesicles with a non-ionic polymer. Colloids Surf. B Biointerfaces, 2014, 114, 45-52. doi:10.1016/j.colsurfb.2013.09.054http://dx.doi.org/10.1016/j.colsurfb.2013.09.054

Wytrwal M.; Bednar J.; Nowakowska M.; Wydro P.; Kepczynski M. Interactions of serum with polyelectrolyte-stabilized liposomes: Cryo-TEM studies. Colloids Surf. B Biointerfaces, 2014, 120, 152-159. doi:10.1016/j.colsurfb.2014.02.040http://dx.doi.org/10.1016/j.colsurfb.2014.02.040

Marie E.; Landfester K.; Antonietti M. Synthesis of chitosan-stabilized polymer dispersions, capsules, and chitosan grafting products via miniemulsion. Biomacromolecules, 2002, 3(3), 475-481. doi:10.1021/bm015634shttp://dx.doi.org/10.1021/bm015634s

Ali S. I.; Heuts J. P. A.; van Herk A. M. Controlled synthesis of polymeric nanocapsules by RAFT-based vesicle templating. Langmuir, 2010, 26(11), 7848-7858. doi:10.1021/la904709chttp://dx.doi.org/10.1021/la904709c

Ruysschaert T.; Paquereau L.; Winterhalter M.; Fournier D. Stabilization of liposomes through enzymatic polymerization of DNA. Nano Lett., 2006, 6(12), 2755-2757. doi:10.1021/nl061724xhttp://dx.doi.org/10.1021/nl061724x

Hub H. H.; Hupfer B.; Koch H.; Ringsdorf H. Polymerizable phospholipid analogues—new stable biomembrane and cell models. Angew. Chem. Int. Ed., 1980, 19(11), 938-940. doi:10.1002/anie.198009381http://dx.doi.org/10.1002/anie.198009381

Graff A.; Winterhalter M.; Meier W. Nanoreactors from polymer-stabilized liposomes. Langmuir, 2001, 17(3), 919-923. doi:10.1021/la001306mhttp://dx.doi.org/10.1021/la001306m

Hotz J.; Meier W. Vesicle-templated polymer hollow spheres. Langmuir, 1998, 14(5), 1031-1036. doi:10.1021/la971080whttp://dx.doi.org/10.1021/la971080w

Cheng Z. L.; D'Ambruoso G. D.; Aspinwall C. A. Stabilized porous phospholipid nanoshells. Langmuir, 2006, 22(23), 9507-9511. doi:10.1021/la061542ihttp://dx.doi.org/10.1021/la061542i

Ghosh S.; Wang X. M.; Wang J. Y.; Nguyen P. D.; Janczak C. M.; Aspinwall C. A. Enhanced fluorescent protein activity in polymer scaffold-stabilized phospholipid nanoshells using neutral redox initiator polymerization conditions. ACS Omega, 2018, 3(11), 15890-15899. doi:10.1021/acsomega.8b01661http://dx.doi.org/10.1021/acsomega.8b01661

Dong Y. C.; Sun Y. W.; Wang L. Y.; Wang D. M.; Zhou T.; Yang Z. Q.; Chen Z.; Wang Q. B.; Fan Q. H.; Liu D. S. Frame-guided assembly of vesicles with programmed geometry and dimensions. Angew. Chem. Int. Ed., 2014, 53(10), 2607-2610. doi:10.1002/anie.201310715http://dx.doi.org/10.1002/anie.201310715

Dong Y. C.; Yang Y.; Lin C. X.; Liu D. S. Frame-guided assembly of amphiphiles. Acc. Chem. Res., 2022, 55(14), 1938-1948. doi:10.1021/acs.accounts.2c00234http://dx.doi.org/10.1021/acs.accounts.2c00234

Dong Y. C.; Liu D. S. Frame-guided assembly of amphiphiles. Chem. Eur. J., 2015, 21(50), 18018-18023. doi:10.1002/chem.201501849http://dx.doi.org/10.1002/chem.201501849

Piao J. F.; Yuan W.; Dong Y. C. Recent progress of DNA nanostructures on amphiphilic membranes. Macromol. Biosci., 2021, 21(5), 2000440. doi:10.1002/mabi.202200146http://dx.doi.org/10.1002/mabi.202200146

Zhou C.; Zhang Y. Y.; Dong Y. C.; Wu F.; Wang D. M.; Xin L.; Liu D. S. Precisely controlled 2d free-floating nanosheets of amphiphilic molecules through frame-guided assembly. Adv. Mater., 2016, 28(44), 9819-9823. doi:10.1002/adma.201603210http://dx.doi.org/10.1002/adma.201603210

Dong Y. C.; Yang Y. R.; Zhang Y. Y.; Wang D. M.; Wei X. X.; Banerjee S.; Liu Y.; Yang Z. Q.; Yan H.; Liu D. S. Cuboid vesicles formed by frame-guided assembly on DNA origami scaffolds. Angew. Chem. Int. Ed., 2017, 56(6), 1586-1589. doi:10.1002/anie.201610133http://dx.doi.org/10.1002/anie.201610133

Yang Y.; Wang J.; Shigematsu H.; Xu W. M.; Shih W. M.; Rothman J. E.; Lin C. X. Self-assembly of size-controlled liposomes on DNA nanotemplates. Nat. Chem., 2016, 8(5), 476-483. doi:10.1038/nchem.2472http://dx.doi.org/10.1038/nchem.2472

Wu F.; Jin J.; Wang L. Y.; Sun P. F.; Yuan H. X.; Yang Z. Q.; Chen G. S.; Fan Q. H.; Liu D. S. Functionalization of DNA-dendron supramolecular fibers and application in regulation of Escherichia Coli association. ACS Appl. Mater. Interfaces, 2015, 7(13), 7351-7356. doi:10.1021/acsami.5b00702http://dx.doi.org/10.1021/acsami.5b00702

Dong Y. C.; Yang Z. Q.; Liu D. S. Using small molecules to prepare vesicles with designable shapes and sizes via frame-guided assembly strategy. Small, 2015, 11(31), 3768-3771. doi:10.1002/smll.201500240http://dx.doi.org/10.1002/smll.201500240

Zhao Z. Y.; Chen C.; Dong Y. C.; Yang Z. Q.; Fan Q. H.; Liu D. S. Thermally triggered frame-guided assembly. Angew. Chem. Int. Ed., 2014, 53(49), 13468-13470. doi:10.1002/anie.201408231http://dx.doi.org/10.1002/anie.201408231

Zhang Z.; Yang Y.; Pincet F.; Llaguno M. C.; Lin C. X. Placing and shaping liposomes with reconfigurable DNA nanocages. Nat. Chem., 2017, 9(7), 653-659. doi:10.1038/nchem.2802http://dx.doi.org/10.1038/nchem.2802

Wang C.; Piao J. F.; Li Y. J.; Tian X. C.; Dong Y. C.; Liu D. S. Construction of liposomes mimicking cell membrane structure through frame-guided assembly. Angew. Chem. Int. Ed., 2020, 59(35), 15176-15180. doi:10.1002/anie.202005334http://dx.doi.org/10.1002/anie.202005334

Shi J. Z.; Jia H. Y.; Chen H.; Wang X.; Xu J. F.; Ren W. B.; Zhao J.; Zhou X.; Dong Y. C.; Liu D. S. Concentration insensitive supramolecular polymerization enabled by kinetically interlocking multiple units strategy. CCS Chem., 2019, 1(3), 296-303. doi:10.31635/10.31635/ccschem.019.20190009http://dx.doi.org/10.31635/10.31635/ccschem.019.20190009

Li Y. J., Ding Y. Q., Yang B., Cao T. Y., Xu J. F., Dong Y. C., Chen Q., Xu L. J., Liu D. S.; Reinforcing DNA supramolecular hydrogel with polymeric multiple-unit linker. CCS Chem., 2022, Doi: 10.31635/ccschem.022.202101523http://dx.doi.org/10.31635/ccschem.022.202101523.

Wang H. Y.; Jia H. R.; Lu X. L.; Chen B.; Zhou G. X.; He N. Y.; Chen Z.; Wu F. G. Imaging plasma membranes without cellular internalization: multisite membrane anchoring reagents based on glycol chitosan derivatives. J. Mater. Chem. B, 2015, 3(30), 6165-6173. doi:10.1039/c5tb00930hhttp://dx.doi.org/10.1039/c5tb00930h

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