Daidzein Polymer Prodrugs: Synthesis and Their Antibacterial and Anti-inflammatory Biological Applications

Fan Wu; Yuan-Feng Li; Lin-qi Shi; Yong Liu

doi:10.11777/j.issn1000-3304.2024.24307

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Daidzein Polymer Prodrugs: Synthesis and Their Antibacterial and Anti-inflammatory Biological Applications

更新时间：2025-03-21

- Daidzein Polymer Prodrugs: Synthesis and Their Antibacterial and Anti-inflammatory Biological Applications
- Acta Polymerica Sinica Pages: 1-11(2025)
- 作者机构：
  
  1.南开大学药物化学生物学全国重点实验室天津 300071
  2.温州医科大学附属第一医院转化医学实验室温州 325000
- 作者简介：
  
  Yong Liu, E-mail: y.liu@nankai.edu.cn
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2024.24307
  CLC：
- CSTR：32057.14.GFZXB.2025.7344
- Received：23 December 2024，
  
  Accepted：2025-01-15，
  
  Published Online：21 March 2025，
- 稿件说明：
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伍凡, 李圆凤, 史林启, 刘勇. 大豆苷元聚合物前药：合成及其抗菌消炎生物应用研究. 高分子学报, doi: 10.11777/j.issn1000-3304.2024.24307

Wu, F.; Li, Y. F.; Shi, L. Q.; Liu, Y. Daidzein polymer prodrugs: synthesis and their antibacterial and anti-inflammatory biological applications. Acta Polymerica Sinica, doi: 10.11777/j.issn1000-3304.2024.24307
伍凡, 李圆凤, 史林启, 刘勇. 大豆苷元聚合物前药：合成及其抗菌消炎生物应用研究. 高分子学报, doi: 10.11777/j.issn1000-3304.2024.24307 DOI： CSTR： 32057.14.GFZXB.2025.7344.

Wu, F.; Li, Y. F.; Shi, L. Q.; Liu, Y. Daidzein polymer prodrugs: synthesis and their antibacterial and anti-inflammatory biological applications. Acta Polymerica Sinica, doi: 10.11777/j.issn1000-3304.2024.24307 DOI： CSTR： 32057.14.GFZXB.2025.7344.

摘要

针对细菌感染治疗中对抗菌和消炎一体化系统的需求

以及聚合物前药在合成方面的局限性

本研究设计并构建了一种主链含有大豆苷元(Daidzein

Dai)的三嵌段聚-

-氨基酯(Dai-encapsulating poly-

β‍

-amino ester

D-PAE). D-PAE纳米药物的叔胺片段在细菌感染的酸性环境中能够质子化

转变为正电荷; 同时

感染部位高表达的细菌酯酶能够水解其主链中的酯键

释放出Dai

从而发挥高效的抗菌和消炎作用. 体外与体内实验表明

D-PAE 纳米药物相比于纯药具有更高的生物活性

并且表现出良好的生物相容性. 本研究为聚合物前药的设计

合成及其生物医用提供了重要参考与新思路.

Abstract

To address the need for an integrated antibacterial and anti-inflammatory approach in treating bacterial infections

this study developed a novel triblock poly-‍

β‍

-amino ester (Dai-encapsulating poly-‍

β‍‍

-amino ester

D-PAE) incorporating daidzein into the polymer backbone. Daidzein is a bioactive compound with known antibacterial and anti-inflammatory properties. The D-PAE nanoparticles utili

ze a unique mechanism where the tertiary amine segments of the polymer undergo protonation in the acidic microenvironment of bacterial infection sites

resulting in a positive charge. This enhances the nanoparticles' interaction with the negatively charged bacterial membranes

facilitating targeted drug delivery. Additionally

bacterial lipases

which are overexpressed at infection sites

hydrolyze the ester bonds in the polymer backbone

triggering the controlled release of daidzein.Once released

daidzein exerts its antibacterial effects by inhibiting bacterial growth and biofilm formation

while also reducing inflammation by modulating the immune response. This dual action helps to address both the bacterial infection and the inflammatory damage associated with it.

In vitro

and

in vivo

studies demonstrated that D-PAE nanoparticles exhibit superior bioactivity and biocompatibility compared to the free drug. The nanoparticles are more efficient in delivering daidzein directly to the infection site

offering prolonged therapeutic effects with reduced toxicity to healthy tissues.This study offers an innovative approach to overcoming the limitations of conventional polymeric prodrugs. By incorporating daidzein into a polymeric matrix

D-PAE nanoparticles provide a more effective and targeted solution for bacterial infections

addressing both the bacterial presence and the associated inflammation. The results highlight the potential for this strategy to be expanded to other therapeutic applications

offering a valuable reference for future designs in drug delivery systems. These findings open new avenues for the development of advanced prodrug systems that combine multiple therapeutic actions for improved patient outcomes.

关键词

Keywords

references

Zhou C. Y. ; Liu Y. ; Li Y. F. ; Shi L. Q. Recent advances and prospects in nanomaterials for bacterial sepsis management . J. Mater. Chem. B , 2023 , 11 ( 45 ), 10778 - 10792 . doi: 10.1039/d3tb02220j http://dx.doi.org/10.1039/d3tb02220j

Chen L. ; Peng M. N. ; He W. ; Hu X. L. ; Xiao J. ; Shi L. Q. ; Liu Y. ; Li Y. F. Microenvironment-adaptive nanodecoy synergizes bacterial eradication, inflammation alleviation, and immunomodulation in promoting biofilm-associated diabetic chronic wound healing cascade . Aggregate , 2024 , 5 ( 6 ), e 640 . doi: 10.1002/agt2.640 http://dx.doi.org/10.1002/agt2.640

Wu H. Y. ; Liu Y. ; Wang Y. M. ; Piao Y. Z. ; Meng Z. J. ; Hu X. W. ; Shi L. Q. ; Shen J. ; Li Y. F. Dynamic covalent prodrug nanonetworks via reaction-induced self-assembly for periodontitis treatment . ACS Nano , 2024 , 18 ( 51 ), 34884 - 34901 . doi: 10.1021/acsnano.4c12580 http://dx.doi.org/10.1021/acsnano.4c12580

Zhang X. N. ; Ren K. X. ; Xiao C. S. ; Chen X. S. Guanosine-driven hyaluronic acid-based supramolecular hydrogels with peroxidase-like activity for chronic diabetic wound treatment . Acta Biomater. , 2023 , 172 , 206 - 217 . doi: 10.1016/j.actbio.2023.10.014 http://dx.doi.org/10.1016/j.actbio.2023.10.014

Wang Y. ; Yang Y. N. ; Shi Y. R. ; Song H. ; Yu C. Z. Antibiotic-free antibacterial strategies enabled by nanomaterials: progress and perspectives . Adv. Mater. , 2020 , 32 ( 18 ), 1904106 . doi: 10.1002/adma.202070138 http://dx.doi.org/10.1002/adma.202070138

杜佳强 , 张彦峰 , 成一龙 . 聚硫辛酸基多功能水凝胶的构建及在感染皮肤伤口修复中的应用 . 高分子学报 , 2024 , 55 ( 5 ), 624 - 636 .

Wan P. Q. ; Guo W. ; Wang Y. J. ; Deng M. X. ; Xiao C. S. ; Chen X. S. Photosensitizer-polypeptide conjugate for effective elimination of candida albicans biofilm . Adv. Healthc. Mater. , 2022 , 11 ( 16 ), e 2200268 . doi: 10.1002/adhm.202200268 http://dx.doi.org/10.1002/adhm.202200268

Liu Y. ; Shi L. Q. ; Su L. Z. ; van der Mei H. C. ; Jutte P. C. ; Ren Y. J. ; Busscher H. J. Nanotechnology-based antimicrobials and delivery systems for biofilm-infection control . Chem. Soc. Rev. , 2019 , 48 ( 2 ), 428 - 446 . doi: 10.1039/c7cs00807d http://dx.doi.org/10.1039/c7cs00807d

Chen Y. C. ; Gao Y. F. ; Huang Y. ; Jin Q. ; Ji J. Inhibiting quorum sensing by active targeted pH-sensitive nanoparticles for enhanced antibiotic therapy of biofilm-associated bacterial infections . ACS Nano , 2023 , 17 ( 11 ), 10019 - 10032 . doi: 10.1021/acsnano.2c12151 http://dx.doi.org/10.1021/acsnano.2c12151

廖宇思 , 梁剑箫 , 温转 , 蔡明泽 , 宋张志 , 张薿元 , 安红维 , 王浩 . 生物医用高分子材料细胞膜表面功能化的策略与应用 . 高分子学报 , 2024 , 55 ( 5 ), 553 - 572 .

Bi Y. F. ; Xia G. X. ; Shi C. ; Wan J. L. ; Liu L. Q. ; Chen Y. ; Wu Y. M. ; Zhang W. J. ; Zhou M. ; He H. Y. ; Liu R. H. Therapeutic strategies against bacterial biofilms . Fundam. Res. , 2021 , 1 ( 2 ), 193 - 212 . doi: 10.1016/j.fmre.2021.02.003 http://dx.doi.org/10.1016/j.fmre.2021.02.003

Shao N. ; Yuan L. ; Ma P. C. ; Zhou M. ; Xiao X. M. ; Cong Z. H. ; Wu Y. M. ; Xiao G. H. ; Fei J. ; Liu R. H. Heterochiral β -peptide polymers combating multidrug-resistant cancers effectively without inducing drug resistance . J. Am. Chem. Soc. , 2022 , 144 ( 16 ), 7283 - 7294 . doi: 10.1021/jacs.2c00452 http://dx.doi.org/10.1021/jacs.2c00452

Su L. Z. ; Liu Y. ; Li Y. F. ; An Y. L. ; Shi L. Q. Responsive polymeric nanoparticles for biofilm-infection control . Chinese J. Polym. Sci. , 2021 , 39 ( 11 ), 1376 - 1391 . doi: 10.1007/s10118-021-2610-3 http://dx.doi.org/10.1007/s10118-021-2610-3

Shi Q. Q. ; Yin H. ; Song R. D. ; Xu J. ; Tan J. J. ; Zhou X. ; Cen J. ; Deng Z. Y. ; Tong H. M. ; Cui C. H. ; Zhang Y. F. ; Li X. P. ; Zhang Z. B. ; Liu S. Y. Digital micelles of encoded polymeric amphiphiles for direct sequence reading and ex vivo label-free quantification . Nat. Chem. , 2023 , 15 ( 2 ), 257 - 270 . doi: 10.1038/s41557-022-01076-y http://dx.doi.org/10.1038/s41557-022-01076-y

Cheng J. ; Gan G. H. ; Zheng S. Q. ; Zhang G. Y. ; Zhu C. ; Liu S. Y. ; Hu J. M. Biofilm heterogeneity-adaptive photoredox catalysis enables red light-triggered nitric oxide release for combating drug-resistant infections . Nat. Commun. , 2023 , 14 ( 1 ), 7510 . doi: 10.1038/s41467-023-43415-8 http://dx.doi.org/10.1038/s41467-023-43415-8

Cao B. ; Xiao F. F. ; Xing D. ; Hu X. L. Polyprodrug antimicrobials: remarkable membrane damage and concurrent drug release to combat antibiotic resistance of methicillin-resistant staphylococcus aureus . Small , 2018 , 14 ( 41 ), 1802008 . doi: 10.1002/smll.201870186 http://dx.doi.org/10.1002/smll.201870186

Seidi F. ; Zhong Y. J. ; Xiao H. N. ; Jin Y. C. ; Crespy D. Degradable polyprodrugs: design and therapeutic efficiency . Chem. Soc. Rev. , 2022 , 51 ( 15 ), 6652 - 6703 . doi: 10.1039/d2cs00099g http://dx.doi.org/10.1039/d2cs00099g

Shi Q. Q. ; Zhou X. ; Xu J. ; Wang N. ; Zhang J. L. ; Hu X. L. ; Liu S. Y. Controlled fabrication of uniform digital nanorods from precise sequence-defined amphiphilic polymers in aqueous media . Chinese J. Polym. Sci. , 2023 , 41 ( 5 ), 768 - 777 . doi: 10.1007/s10118-023-2946-y http://dx.doi.org/10.1007/s10118-023-2946-y

Liu Y. ; Ren Y. J. ; Li Y. F. ; Su L. Z. ; Zhang Y. M. ; Huang F. ; Liu J. J. ; Liu J. F. ; van Kooten T. G. ; An Y. L. ; Shi L. Q. ; van der Mei H. C. ; Busscher H. J. Nanocarriers with conjugated antimicrobials to eradicate pathogenic biofilms evaluated in murine in vivo and human ex vivo infection models . Acta Biomater. , 2018 , 79 , 331 - 343 . doi: 10.1016/j.actbio.2018.08.038 http://dx.doi.org/10.1016/j.actbio.2018.08.038

Huang Y. Q. ; Li Y. F. ; Liu Y. ; Shi L. Q. Triclosan-conjugated, lipase-responsive polymeric micelles for eradication of staphylococcal biofilms . Chinese J. Polym. Sci. , 2024 , 42 ( 6 ), 718 - 728 . doi: 10.1007/s10118-024-3094-8 http://dx.doi.org/10.1007/s10118-024-3094-8

Qian Y. H. ; Hu X. L. ; Wang J. H. ; Li Y. F. ; Liu Y. ; Xie L. P. Polyzwitterionic micelles with antimicrobial-conjugation for eradication of drug-resistant bacterial biofilms . Colloids Surf. B Biointerfaces , 2023 , 231 , 113542 . doi: 10.1016/j.colsurfb.2023.113542 http://dx.doi.org/10.1016/j.colsurfb.2023.113542

Yang K. K. ; Yang Z. Q. ; Yu G. C. ; Nie Z. H. ; Wang R. B. ; Chen X. Y. Polyprodrug nanomedicines: an emerging paradigm for cancer therapy . Adv. Mater. , 2022 , 34 ( 6 ), 2107434 . doi: 10.1002/adma.202107434 http://dx.doi.org/10.1002/adma.202107434

Ke W. D. ; Li J. J. ; Mohammed F. ; Wang Y. H. ; Tou K. ; Liu X. Y. ; Wen P. Y. ; Kinoh H. ; Anraku Y. ; Chen H. B. ; Kataoka K. ; Ge Z. S. Therapeutic polymersome nanoreactors with tumor-specific activable cascade reactions for cooperative cancer therapy . ACS Nano , 2019 , 13 ( 2 ), 2357 - 2369 .

Ekladious I. ; Colson Y. L. ; Grinstaff M. W. Polymer-drug conjugate therapeutics: advances, insights and prospects . Nat. Rev. Drug Discov. , 2019 , 18 ( 4 ), 273 - 294 . doi: 10.1038/s41573-018-0005-0 http://dx.doi.org/10.1038/s41573-018-0005-0

Xu X. D. ; Saw P. E. ; Tao W. ; Li Y. J. ; Ji X. Y. ; Bhasin S. ; Liu Y. L. ; Ayyash D. ; Rasmussen J. ; Huo M. ; Shi J. J. ; Farokhzad O. C. ROS-responsive polyprodrug nanoparticles for triggered drug delivery and effective cancer therapy . Adv. Mater. , 2017 , 29 ( 33 ), 1700141 . doi: 10.1002/adma.201700141 http://dx.doi.org/10.1002/adma.201700141

Xiang J. J. ; Liu X. ; Yuan G. P. ; Zhang R. N. ; Zhou Q. ; Xie T. ; Shen Y. Q. Nanomedicine from amphiphilized prodrugs: concept and clinical translation . Adv. Drug Deliv. Rev. , 2021 , 179 , 114027 . doi: 10.1016/j.addr.2021.114027 http://dx.doi.org/10.1016/j.addr.2021.114027

Deng Z. Y. ; Liu S. Y. Controlled drug delivery with nanoassemblies of redox-responsive prodrug and polyprodrug amphiphiles . J. Control. Release , 2020 , 326 , 276 - 296 . doi: 10.1016/j.jconrel.2020.07.010 http://dx.doi.org/10.1016/j.jconrel.2020.07.010

Liu Y. ; Li Y. F. ; Keskin D. ; Shi L. Q. Poly( β -amino esters): synthesis, formulations, and their biomedical applications . Adv. Healthcare Mater. , 2019 , 8 ( 2 ), 1801359 . doi: 10.1002/adhm.201801359 http://dx.doi.org/10.1002/adhm.201801359

Li Y. F. ; Piao Y. Z. ; Chen H. ; Shi K. Q. ; Dai J. Q. ; Wang S. R. ; Zhou T. L. ; Le A. T. ; Wang Y. R. ; Wu F. ; Ma R. J. ; Shi L. Q. ; Liu Y. Dynamic covalent nano-networks comprising antibiotics and polyphenols orchestrate bacterial drug resistance reversal and inflammation alleviation . Bioact. Mater. , 2023 , 27 , 288 - 302 . doi: 10.1016/j.bioactmat.2023.04.014 http://dx.doi.org/10.1016/j.bioactmat.2023.04.014

Lynn D. M. ; Langer R. Degradable poly( β -amino esters): synthesis, characterization, and self-assembly with plasmid, DNA . J. Am. Chem. Soc. , 2000 , 122 ( 44 ), 10761 - 10768 . doi: 10.1021/ja0015388 http://dx.doi.org/10.1021/ja0015388

Liu Y. ; Busscher H. J. ; Zhao B. R. ; Li Y. F. ; Zhang Z. K. ; van der Mei H. C. ; Ren Y. J. ; Shi L. Q. Surface-adaptive, antimicrobially loaded, micellar nanocarriers with enhanced penetration and killing efficiency in staphylococcal biofilms . ACS Nano , 2016 , 10 ( 4 ), 4779 - 4789 . doi: 10.1021/acsnano.6b01370 http://dx.doi.org/10.1021/acsnano.6b01370

Silva L. N. ; Zimmer K. R. ; Macedo A. J. ; Trentin D. S. Plant natural products targeting bacterial virulence factors . Chem. Rev. , 2016 , 116 ( 16 ), 9162 - 9236 . doi: 10.1021/acs.chemrev.6b00184 http://dx.doi.org/10.1021/acs.chemrev.6b00184

Hu X. W. ; Li D. D. ; Li H. P. ; Piao Y. Z. ; Wan H. P. ; Zhou T. L. ; Karimi M. ; Zhao X. H. ; Li Y. F. ; Shi L. Q. ; Liu Y. Reaction-induced self-assembly of polymyxin mitigates cytotoxicity and reverses drug resistance . Adv. Mater. , 2024 , 36 ( 36 ), 2406156 .

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南开大学药物化学生物学全国重点实验室

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