酶触发聚合物囊泡-核交联胶束转变用于响应性抗菌剂释放

李亚民; 刘世勇

doi:10.11777/j.issn1000-3304.2017.17035

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酶触发聚合物囊泡-核交联胶束转变用于响应性抗菌剂释放

研究论文 | 更新时间：2021-01-26

- 酶触发聚合物囊泡-核交联胶束转变用于响应性抗菌剂释放
  增强出版
- Enzyme-triggered Transition from Polymeric Vesicles to Core Cross-linked Micelles for Selective Release of Antimicrobial Agents
- 高分子学报 2017年第7期页码：1178-1190
- 作者机构：
  
  中国科学院软物质化学重点实验室中国科学技术大学高分子科学与工程系合肥 230026
- 作者简介：
  
  刘世勇, E-mail:sliu@ustc.edu.cn Shi-yong Liu, E-mail:sliu@ustc.edu.cn
- 基金信息：
  
  国家自然科学基金(51690150);国家自然科学基金(51690154);国家自然科学基金(21674103);国家重点研发计划“政府间国际科技创新合作”重点专项(2016YFE0129700)
- DOI：10.11777/j.issn1000-3304.2017.17035
  中图分类号：
- 纸质出版日期：2017-7，
  
  收稿日期：2017-3-3，
  
  修回日期：2017-3-21，
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李亚民, 刘世勇. 酶触发聚合物囊泡-核交联胶束转变用于响应性抗菌剂释放[J]. 高分子学报, 2017,(7):1178-1190.

Ya-min Li, Shi-yong Liu. Enzyme-triggered Transition from Polymeric Vesicles to Core Cross-linked Micelles for Selective Release of Antimicrobial Agents[J]. Acta Polymerica Sinica, 2017,(7):1178-1190.
李亚民, 刘世勇. 酶触发聚合物囊泡-核交联胶束转变用于响应性抗菌剂释放[J]. 高分子学报, 2017,(7):1178-1190. DOI： 10.11777/j.issn1000-3304.2017.17035.

Ya-min Li, Shi-yong Liu. Enzyme-triggered Transition from Polymeric Vesicles to Core Cross-linked Micelles for Selective Release of Antimicrobial Agents[J]. Acta Polymerica Sinica, 2017,(7):1178-1190. DOI： 10.11777/j.issn1000-3304.2017.17035.

摘要

通过使用药物运载体系来提高抗菌物质的使用效率是应对抗生素耐药性的有效途径.本文报道了一种制备细菌酶响应聚合物囊泡作为“智能型”抗菌剂载体的方法.通过可逆加成-断裂链转移聚合（RAFT）制备的脂酶和硝基还原酶响应的二嵌段共聚物PEG-

-PA和PEG-

-PN，能够在水溶液中自组装形成聚合物囊泡组装体.该囊泡组装体在没有酶存在的条件下相对稳定，而在脂酶或硝基还原酶的作用下发生从囊泡到核交联胶束的形貌转变.基于这一转变过程实现了负载在囊泡中的抗菌剂（三氯生，抗菌肽Parasin Ⅰ和溶菌酶）的选择性释放，并研究了针对大肠杆菌（

E.coli

，革兰氏阴性菌）、金黄色葡萄球菌（

S.aureus

，革兰氏阳性菌）和白色念珠菌（

C.albicans

，真菌）的生长抑制效果.

Abstract

The optimization of the efficacy of currently available antibiotics by taking advantage of drug delivery systems has emerged as an alternative methodology to combat the severe threat of antimicrobial resistance

which can in part bypass the challenges for developing brand new antimicrobial agents. Herein

we report a new strategy to design and fabricate bacterial enzyme-responsive polymersomes as "smart" antimicrobial delivery carriers. Lipase (

Lip

)-and nitroreductase (

NTR

)-responsive amphiphilic block copolymers (BCPs)

poly(ethylene glycol)-b-poly(2-((((4-acetoxybenzyl)oxy)carbonyl)amino)ethyl methacrylate) (PEG-

-PA) and poly(ethylene glycol)-bpoly(2-((((4-nitrobenzyl)oxy)carbonyl)amino)ethyl methacrylate) (PEG-

-PN)

consisting of enzyme-reactive pendent chains

were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization. The resultant BCPs self-assembled into vesicles with hydrophilic PEG coronas and hydrophobic enzyme-reactive bilayers. The as-assembled vesicles were relatively stable in aqueous solution but they underwent enzymatic degradation with the formation of core cross-linked (CCL) micelles through aminolysis reaction from decaged carbamate linkages. Several antimicrobial agents

including hydrophobic triclosan (TCN)

hydrophilic antibacterial peptide (Parasin Ⅰ)

and therapeutic protein lysozyme (

Lyz

)

were encapsulated into the enzymeresponsive polymersomes either within the aqueous interiors or hydrophobic bilayer membranes. We demonstrated that the enhanced release of encapsulated antibacterial agents as well as antimicribial activities against Gram-negative (

E.coli

)

Gram-positive (

S.aureus

) bacteria

and fungi (

C.albicans

)

could be achieved when triggered by

Lip

NTR

关键词

聚合物囊泡酶响应纳米药物载体细菌耐药性抗菌剂

Keywords

VesiclesEnzyme-responsiveDrug nanocarriersBacterial drug resistanceAntimicrobial agents

references

S B Levy , B Marshall . . Nat Med , 2004 . 10 ( 12 ): S122 - S129.

D I Andersson , D Hughes . . Nat Rev Microbiol , 2010 . 8 ( 4 ): 260 - 271.

J L Martinez . . Science , 2008 . 321 ( 5887 ): 365 - 367 . DOI:10.1126/science.1159483http://doi.org/10.1126/science.1159483.

L Zhang , D Pornpattananangkul , C M J Hu , C M Huang . . Curr Med Chem , 2010 . 17 ( 6 ): 585 - 594 . DOI:10.2174/092986710790416290http://doi.org/10.2174/092986710790416290.

A L Armstead , B Y Li . . Int J Nanomed , 2011 . ( 6 ): 3281 - 3293.

X H Fu , Y Shen , Y A Ma , W X Fu , Z B Li . . Sci China Chem , 2015 . 58 ( 6 ): 1005 - 1012 . DOI:10.1007/s11426-014-5297-2http://doi.org/10.1007/s11426-014-5297-2.

Y J Gao , Z Y Qiao , H Wang . . Sci China Chem , 2016 . 59 ( 8 ): 991 - 1002 . DOI:10.1007/s11426-015-0516-2http://doi.org/10.1007/s11426-015-0516-2.

P F Sun , M C Lin , G S Chen , M Jiang . . Sci China Chem , 2016 . 59 ( 12 ): 1616 - 1620 . DOI:10.1007/s11426-016-0117-5http://doi.org/10.1007/s11426-016-0117-5.

H Chang , M Shi , Y N Sun , J Q Jiang . . Chinese J Polym Sci , 2015 . 33 ( 8 ): 1086 - 1095 . DOI:10.1007/s10118-015-1657-4http://doi.org/10.1007/s10118-015-1657-4.

X X Ke , J T Xu , B Y Du , Z Q Fan . . Chinese J Polym Sci , 2015 . 33 ( 7 ): 1038 - 1047 . DOI:10.1007/s10118-015-1656-5http://doi.org/10.1007/s10118-015-1656-5.

W C Wang , K Shi , Y X Pan , C Peng , Z L Zhao , W Liu , Y G Liu , X N Ji . . Chinese J Polym Sci , 2016 . 34 ( 4 ): 475 - 482 . DOI:10.1007/s10118-016-1769-5http://doi.org/10.1007/s10118-016-1769-5.

L Wang , H K Zhang , A J Qin , Q Jin , B Z Tang , J Ji . . Sci China Chem , 2016 . 59 ( 12 ): 1609 - 1615 . DOI:10.1007/s11426-016-0246-9http://doi.org/10.1007/s11426-016-0246-9.

L H Zhang , C Gu , R Hong , H P Zhang . . Sci China Chem , 2015 . 58 ( 7 ): 1220 - 1226 . DOI:10.1007/s11426-014-5238-0http://doi.org/10.1007/s11426-014-5238-0.

Y Y Zhuang , D L Wang , C H Yin , H P Deng , M Sun , L He , Y Su , X Y Zhu . . Sci China Chem , 2016 . 59 ( 12 ): 1600 - 1608 . DOI:10.1007/s11426-016-0228-0http://doi.org/10.1007/s11426-016-0228-0.

R C Mundargi , S Srirangarajan , S A Agnihotri , S A Patil , S Ravindra , S B Setty , T M Aminabhavi . . J Control Release , 2007 . 119 ( 1 ): 59 - 68 . DOI:10.1016/j.jconrel.2007.01.008http://doi.org/10.1016/j.jconrel.2007.01.008.

S Giovagnoli , T Tsai , P P DeLuca . . AAPS Pharm Sci Tech , 2010 . 11 ( 1 ): 212 - 220 . DOI:10.1208/s12249-009-9361-8http://doi.org/10.1208/s12249-009-9361-8.

M Gillissen , R Steendam , der Laan A van , E Tijsma . . J Control Release , 2006 . 116 ( 2 ): E90 - E92 . DOI:10.1016/j.jconrel.2006.09.066http://doi.org/10.1016/j.jconrel.2006.09.066.

F Bigucci , B Luppi , A Musenga , V Zecchi , T Cerchiara . . Drug Deliv , 2008 . 15 ( 5 ): 289 - 293 . DOI:10.1080/10717540802006468http://doi.org/10.1080/10717540802006468.

R J R W Peters , M Marguet , S Marais , M W Fraaije , Hest J C M van , S Lecommandoux . . Angew Chem Int Ed , 2014 . 53 ( 1 ): 146 - 150 . DOI:10.1002/anie.v53.1http://doi.org/10.1002/anie.v53.1.

G H Liu , X R Wang , J M Hu , G Y Zhang , S Y Liu . . J Am Chem Soc , 2014 . 136 ( 20 ): 7492 - 7497 . DOI:10.1021/ja5030832http://doi.org/10.1021/ja5030832.

K T Kim , J J L M Cornelissen , R J M Nolte , Hest J C M van . . Adv Mater , 2009 . 21 ( 27 ): 2787 - 2791 . DOI:10.1002/adma.200900300http://doi.org/10.1002/adma.200900300.

E G Bellomo , M D Wyrsta , L Pakstis , D J Pochan , T J Deming . . Nat Mater , 2004 . 3 ( 4 ): 244 - 248 . DOI:10.1038/nmat1093http://doi.org/10.1038/nmat1093.

M Z Wang , T Wang , K Yuan , J Z Du . . Chinese J Polym Sci , 2016 . 34 ( 1 ): 44 - 51 . DOI:10.1007/s10118-016-1725-4http://doi.org/10.1007/s10118-016-1725-4.

C Y Wang , Q Yuan , S G Yang , J Xu . . Chinese J Polym Sci , 2015 . 33 ( 4 ): 661 - 668 . DOI:10.1007/s10118-015-1618-yhttp://doi.org/10.1007/s10118-015-1618-y.

D Pornpattananangkul , L Zhang , S Olson , S Aryal , M Obonyo , K Vecchio , C M Huang , L F Zhang . . J Am Chem Soc , 2011 . 133 ( 11 ): 4132 - 4139 . DOI:10.1021/ja111110ehttp://doi.org/10.1021/ja111110e.

Y M Li , X L Hu , S D Tian , Y Li , G Q Zhang , G Y Zhang , S Y Liu . . Biomaterials , 2014 . 35 ( 5 ): 1618 - 1626 . DOI:10.1016/j.biomaterials.2013.10.077http://doi.org/10.1016/j.biomaterials.2013.10.077.

S Haas , N Hain , M Raoufi , S Handschuh-Wang , T Wang , X Jiang , H Schonherr . . Biomacromolecules , 2015 . 16 ( 3 ): 832 - 841 . DOI:10.1021/bm501729hhttp://doi.org/10.1021/bm501729h.

M Wang , C Zhou , J Chen , Y Xiao , J Du . . Bioconjugate Chem , 2015 . 26 ( 4 ): 725 - 735 . DOI:10.1021/acs.bioconjchem.5b00061http://doi.org/10.1021/acs.bioconjchem.5b00061.

G Baier , A Cavallaro , K Vasilev , V Mailander , A Musyanovych , K Landfester . . Biomacromolecules , 2013 . 14 ( 4 ): 1103 - 1112 . DOI:10.1021/bm302003mhttp://doi.org/10.1021/bm302003m.

K S Tucking , S Handschuh-Wang , H Schonherr . . Aust J Chem , 2014 . 67 ( 4 ): 578 - 584 . DOI:10.1071/CH13527http://doi.org/10.1071/CH13527.

Jie Wang , Huimei Li , Yunzhou Ni , Yongfeng Zhou , Deyue Yan . . Acta Polymerica Sinica , 2016 . ( 7 ): 971 - 978 . http://www.gfzxb.org/CN/abstract/abstract14605.shtml.

王洁 , 李惠梅 , 倪云洲 , 周永丰 , 颜德岳 . . 高分子学报 , 2016 . ( 7 ): 971 - 978 . http://www.gfzxb.org/CN/abstract/abstract14605.shtml.

R J Holt , G T Stewart . . J Gen Microbiol , 1964 . 36 ( 2 ): 203 - 213 . DOI:10.1099/00221287-36-2-203http://doi.org/10.1099/00221287-36-2-203.

L F Chen . . Am J Infect Control , 2013 . 41 ( 5 ): 448 - 451 . DOI:10.1016/j.ajic.2012.06.013http://doi.org/10.1016/j.ajic.2012.06.013.

R Gupta , N Gupta , P Rathi . . Appl Microbiol Biotechnol , 2004 . 64 ( 6 ): 763 - 781 . DOI:10.1007/s00253-004-1568-8http://doi.org/10.1007/s00253-004-1568-8.

G K Joshi , S Vinay . . Res J Biotechnol , 2007 . 2 ( 2 ): 50 - 56.

M Roldan , E Perez-Reinado , F Castillo , C Moreno-Vivian . . FEMS Microbiol Rev , 2008 . 32 ( 3 ): 474 - 500 . DOI:10.1111/j.1574-6976.2008.00107.xhttp://doi.org/10.1111/j.1574-6976.2008.00107.x.

R H F Wong , T Kwong , K H Yau , H Y Au-Yeung . . Chem Commun , 2015 . 51 ( 21 ): 4440 - 4442 . DOI:10.1039/C4CC10345Ahttp://doi.org/10.1039/C4CC10345A.

R Vyhnalkova , A Eisenberg , de Ven T van . . Macromol Biosci , 2011 . 11 ( 5 ): 639 - 651 . DOI:10.1002/mabi.v11.5http://doi.org/10.1002/mabi.v11.5.

D H Yu , X D Yu , C H Wang , X C Liu , Y Xing . . ACS Appl Mater Inter , 2012 . 4 ( 5 ): 2781 - 2787 . DOI:10.1021/am3004363http://doi.org/10.1021/am3004363.

S Samarajeewa , R Shrestha , Y L Li , K L Wooley . . J Am Chem Soc , 2012 . 134 ( 2 ): 1235 - 1242 . DOI:10.1021/ja2095602http://doi.org/10.1021/ja2095602.

E F Palermo , K Kuroda . . Biomacromolecules , 2009 . 10 ( 6 ): 1416 - 1428 . DOI:10.1021/bm900044xhttp://doi.org/10.1021/bm900044x.

X R Wang , G H Liu , J M Hu , G Y Zhang , S Y Liu . . Angew Chem Int Ed , 2014 . 53 ( 12 ): 3138 - 3142 . DOI:10.1002/anie.201310589http://doi.org/10.1002/anie.201310589.

X L Hu , J M Hu , J Tian , Z S Ge , G Y Zhang , K F Luo , S Y Liu . . J Am Chem Soc , 2013 . 135 ( 46 ): 17617 - 17629 . DOI:10.1021/ja409686xhttp://doi.org/10.1021/ja409686x.

G H Liu , X R Wang , J M Hu , G Y Zhang , S Y Liu . . J Am Chem Soc , 2014 . 136 ( 20 ): 7492 - 7497 . DOI:10.1021/ja5030832http://doi.org/10.1021/ja5030832.

X L Hu , G H Liu , Y Li , X R Wang , S Y Liu . . J Am Chem Soc , 2015 . 137 ( 1 ): 362 - 368 . DOI:10.1021/ja5105848http://doi.org/10.1021/ja5105848.

G H Liu , G F Zhang , J M Hu , X R Wang , M Q Zhu , S Y Liu . . J Am Chem Soc , 2015 . 137 ( 36 ): 11645 - 11655 . DOI:10.1021/jacs.5b05060http://doi.org/10.1021/jacs.5b05060.

S Mura , J Nicolas , P Couvreur . . Nat Mater , 2013 . 12 ( 11 ): 991 - 1003 . DOI:10.1038/nmat3776http://doi.org/10.1038/nmat3776.

J M Hu , G Q Zhang , S Y Liu . . Chem Soc Rev , 2012 . 41 ( 18 ): 5933 - 5949 . DOI:10.1039/c2cs35103jhttp://doi.org/10.1039/c2cs35103j.

Y Ding , Y T Kang , X Zhang . . Chem Commun , 2015 . 51 ( 6 ): 996 - 1003 . DOI:10.1039/C4CC05878Jhttp://doi.org/10.1039/C4CC05878J.

X L Hu , H Li , S Z Luo , T Liu , Y Y Jiang , S Y Liu . . Polym Chem , 2013 . 4 ( 3 ): 695 - 706 . DOI:10.1039/C2PY20701Jhttp://doi.org/10.1039/C2PY20701J.

M H Li , P Keller . . Soft Matter , 2009 . 5 ( 5 ): 927 - 937 . DOI:10.1039/b815725ahttp://doi.org/10.1039/b815725a.

la Rica R de , D Aili , M M Stevens . . Adv Drug Del Rev , 2012 . 64 ( 11 ): 967 - 978 . DOI:10.1016/j.addr.2012.01.002http://doi.org/10.1016/j.addr.2012.01.002.

O R Miranda , X N Li , L Garcia-Gonzalez , Z J Zhu , B Yan , U H F Bunz , V M Rotello . . J Am Chem Soc , 2011 . 133 ( 25 ): 9650 - 9653 . DOI:10.1021/ja2021729http://doi.org/10.1021/ja2021729.

S Samarajeewa , R P Zentay , N D Jhurry , A Li , K Seetho , J Zou , K L Wooley . . Chem Commun , 2014 . 50 ( 8 ): 968 - 970 . DOI:10.1039/C3CC46013Dhttp://doi.org/10.1039/C3CC46013D.

K R Raghupathi , M A Azagarsamy , S Thayumanavan . . Chem-Eur J , 2011 . 17 ( 42 ): 11752 - 11760 . DOI:10.1002/chem.v17.42http://doi.org/10.1002/chem.v17.42.

M A Azagarsamy , P Sokkalingam , S Thayumanavan . . J Am Chem Soc , 2009 . 131 ( 40 ): 14184 - 14185 . DOI:10.1021/ja906162uhttp://doi.org/10.1021/ja906162u.

I Rosenbaum , A J Harnoy , E Tirosh , M Buzhor , M Segal , L Frid , R Shaharabani , R J Amir . . J Am Chem Soc , 2015 . 137 ( 6 ): 2276 - 2284 . DOI:10.1021/ja510085shttp://doi.org/10.1021/ja510085s.

A J Harnoy , I Rosenbaum , E Tirosh , Y Ebenstein , R Shaharabani , R Beck , R J Amir . . J Am Chem Soc , 2014 . 136 ( 21 ): 7531 - 7534 . DOI:10.1021/ja413036qhttp://doi.org/10.1021/ja413036q.

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