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双重敏感mPEG-PDPA-P(AAm-co-AN)聚合物自组装体的药物递送

宋佳 张紫薇 张婕 秦飞扬 徐首红

宋 佳, 张紫薇, 张 婕, 秦飞扬, 徐首红. 双重敏感mPEG-PDPA-P(AAm-co-AN)聚合物自组装体的药物递送[J]. 功能高分子学报,2023,36(1):1-11 doi: 10.14133/j.cnki.1008-9357.20220322001
引用本文: 宋 佳, 张紫薇, 张 婕, 秦飞扬, 徐首红. 双重敏感mPEG-PDPA-P(AAm-co-AN)聚合物自组装体的药物递送[J]. 功能高分子学报,2023,36(1):1-11 doi: 10.14133/j.cnki.1008-9357.20220322001
SONG Jia, ZHANG Ziwei, ZHANG Jie, QIN Feiyang, XU Shouhong. Self-Assembly of Dual-Sensitive mPEG-PDPA-P(AAm-co-AN) for Drug Delivery[J]. Journal of Functional Polymers. doi: 10.14133/j.cnki.1008-9357.20220322001
Citation: SONG Jia, ZHANG Ziwei, ZHANG Jie, QIN Feiyang, XU Shouhong. Self-Assembly of Dual-Sensitive mPEG-PDPA-P(AAm-co-AN) for Drug Delivery[J]. Journal of Functional Polymers. doi: 10.14133/j.cnki.1008-9357.20220322001

双重敏感mPEG-PDPA-P(AAm-co-AN)聚合物自组装体的药物递送

doi: 10.14133/j.cnki.1008-9357.20220322001
基金项目: 国家自然科学基金(22078087)
详细信息
    作者简介:

    宋佳:宋 佳(1997—),女,硕士生,主要研究方向为智能药物载体设计与合成。E-mail:sjzly1016@163.com

    通讯作者:

    徐首红,E-mail:xushouhong@ecust.edu.cn

  • 中图分类号: O648.2

Self-Assembly of Dual-Sensitive mPEG-PDPA-P(AAm-co-AN) for Drug Delivery

  • 摘要: 设计合成了一种新型两亲性三嵌段ABC聚合物聚乙二醇单甲醚-聚甲基丙烯酸二异丙胺基乙酯-聚(丙烯酰胺-co-丙烯腈)(mPEG-PDPA-P(AAm-co-AN))。该聚合物具有pH敏感嵌段PDPA和温度敏感嵌段P(AAm-co-AN),临界溶解温度(UCST)较高,且可以通过改变单体比例来调节UCST。在室温、中性环境下,该聚合物通过自组装形成刺激响应型胶束,可用于抗肿瘤药物的控释研究。温度升高诱导聚合物胶束向不对称囊泡结构转变,pH降低促使聚合物形成更加松散的胶束。在体外释药探究中,聚合物胶束对亲水药物阿霉素(DOX)和疏水药物槲皮素都具有良好的载药效果,在37 ℃、pH=7.4的条件下泄漏量低,随着温度升高和pH降低,胶束释放药物的速率和释放量明显增加。

     

  • 图  1  聚合物mPEG-PDPA-P(AAm-co-AN)溶液在不同环境下的自组装结构

    Figure  1.  Self-assembled structures of polymer mPEG-PDPA-P(AAm-co-AN) solution in different environments

    图  2  mPEG-PDPAk-P(AAmm-co-ANn)的合成路线

    Figure  2.  Synthesis route of mPEG-PDPAk-P(AAmm-co-ANn)

    图  3  (a) mPEG-PDPAk-Br在CDCl3中与 (b) mPEG-PDPAk-P(AAmm-co-ANn)在DMSO中的1H-NMR谱图

    Figure  3.  1H-NMR spectra of (a) mPEG-PDPAk-Br in CDCl3 and (b) mPEG-PDPAk-P(AAmm-co-ANn) in DMSO

    图  4  聚合物的FT-IR谱图

    Figure  4.  FT-IR spectra of polymers

    图  5  (a) 聚合物P1在不同温度、不同质量浓度下的透射率曲线(pH=3.0);(b) 聚合物P1~P4在不同温度下的透射率曲线(pH=3.0,1.0 mg/mL)

    Figure  5.  (a) Transmittance curves of polymer P1 at different temperatures and different mass concentrations (pH=3.0); (b) Transmittance curves of polymer P1~P4 at different temperatures (pH=3.0, 1.0 mg/mL)

    图  6  (a) mPEG-PDPAk-Br在不同pH下透射率曲线;(b) 聚合物P3在不同温度下的透射率曲线(聚合物质量浓度为1.0 mg/mL)

    Figure  6.  (a) Transmittance curve of mPEG-PDPAk-Br at different pH values; (b) Transmittance curves of polymer P3 at different temperatures (the mass concentration of polymer is 1.0 mg/mL)

    图  7  P3胶束在 (a) 不同温度、pH 7.4条件下和 (b) 在不同pH、25 ℃下的粒径分布(聚合物质量浓度为1.0 mg/mL)

    Figure  7.  Particle size distribution of P3 micelles at (a) different temperatures, pH 7.4 and (b) different pH values 25 ℃ (the mass concentration of polymer is 1.0 mg/mL)

    图  8  P3胶束在 (a) 37 ℃,pH 7.4;(b) 45 ℃,pH 7.4;(c) 37 ℃,pH 5.0;(d) 45 ℃,pH 5.0的TEM图

    Figure  8.  TEM images of P3 micelles at (a) 37 ℃, pH 7.4; (b) 45 ℃, pH 7.4; (c) 37 ℃, pH 5.0; (d) 45 ℃, pH 5.0

    图  9  (a) 聚合物胶束在不同pH和不同温度下的DOX累积释放率动力学曲线;(b) 聚合物胶束多阶段pH和温度响应的累积释放率

    Figure  9.  (a) Kinetic curves of DOX cumulative release of polymer micelles at different pH values and different temperatures; (b) Multi-stage pH and temperature response of cumulative release of polymer micelles

    图  10  聚合物胶束在不同pH和不同温度下的槲皮素累积释放率动力学曲线

    Figure  10.  Kinetic curves of quercetin cumulative release of polymer micelles at different pH values and different temperatures

    表  1  聚合物mPEG-PDPAk-P(AAmm-co-ANn)的性质

    Table  1.   Properties of the mPEG-PDPAk-P(AAmm-co-ANn) polymers

    Samplen(AAm)∶n(AN)∶$n({ {\rm{mPEG\text{-}PDPA} }_{k}\text{-}{\rm{Br} } })$MnUCST/℃CMC/(mg·L−1)
    P11125∶375∶110.4×104242.14
    P21050∶450∶110.6×104505.24
    P3500∶214∶15.3×104440.68
    P4350∶150∶14.2×104310.12
    下载: 导出CSV

    表  2  P3胶束在不同环境下的粒径和PDI

    Table  2.   Particle size and PDI of P3 micelles in different environments

    pHSize/nmPDI
    25 ℃37 ℃45 ℃25 ℃37 ℃45 ℃
    7.4134.6±2.5127.7±0.8108.5±2.70.38±0.040.30±0.010.25±0.01
    6.0619.7±37563.9±5.8827.5±13.70.49±0.070.42±0.060.38±0.04
    5.0803±5.3935.3±23.81058±17.670.90±0.060.73±0.020.57±0.01
    下载: 导出CSV

    表  3  聚合物P3胶束在不同温度和不同pH下的Zeta电位

    Table  3.   Zeta potentials of polymeric micelles P3 at different temperatures and pH values

    pHZeta potential/mV
    25 ℃37 ℃45 ℃
    7.4−0.57−1.78−2.14
    6.62.040.55−0.22
    5.67.516.835.37
    下载: 导出CSV
  • [1] XIA C, DONG X, LI H, CAO M, SUN D, HE S, YANG F, YAN X, ZHANG S, LI N, CHEN W. Cancer statistics in China and United States, 2022: Profiles, trends, and determinants [J]. Chin Med J (Eng),2022,135(5):584-590. doi: 10.1097/CM9.0000000000002108
    [2] AKBARI E, MOUSAZADEH H, SABET Z, FATTAHI T, DEHNAD E, AKBARZADEH A, ALIZADEH E. Dual drug delivery of trapoxin A and methotrexate from biocompatible PLGA-PEG polymeric nanoparticles enhanced antitumor activity in breast cancer cell line [J]. Journal of Drug Delivery Science and Technology,2021,61:102294. doi: 10.1016/j.jddst.2020.102294
    [3] KAUR J, MISHRA V, SINGH S K, GULATI M, KAPOOR B, CHELLAPPAN E K, GOWTHAMARAJAN K. Harnessing amphiphilic polymeric micelles for diagnostic and therapeutic applications: Breakthroughs and bottlenecks [J]. J Control Release,2021,334:64-95. doi: 10.1016/j.jconrel.2021.04.014
    [4] LI H J, DU J Z, LIU J, DU X, SONG S, ZHU Y, WANG X, YE X, NIE S, WANG J. Smart superstructures with ultrahigh pH-sensitivity for targeting acidic tumor microenvironment: Instantaneous size switching and improved tumor penetration [J]. ACS Nano,2016,10(7):6753-6761. doi: 10.1021/acsnano.6b02326
    [5] KARIMI M, SAHANDI ZANGABAD P, GHASEMI A, AMIRI M, BAHEAMI M, MALEKZAD H, GHAHRAMANZADEH A, MAHDIEH, BOZORGOMID M, GHASEMI A, HAMBLIN H. Temperature-responsive smart nanocarriers for delivery of therapeutic agents: Applications and recent advances [J]. ACS Appl Mater Interfaces,2016,8(33):21107-21133. doi: 10.1021/acsami.6b00371
    [6] CHEN Z, WAN L, YUAN Y, YING K, XU X, TIAO L, LIU J, XU Z, JIANG B, CAO L. pH/GSH-dual-sensitive hollow mesoporous silica nanoparticle-based drug delivery system for targeted cancer therapy [J]. ACS Biomater Sci Eng,2020,6(6):3375-3387. doi: 10.1021/acsbiomaterials.0c00073
    [7] WANG F, YANG Z, LIU M, TAO Y, LI Z, WU Z, SHUANG Y. Facile nose-to-brain delivery of rotigotine-loaded polymer micelles thermosensitive hydrogels: In vitro characterization and in vivo behavior study [J]. Int J Pharm,2020,577:119046. doi: 10.1016/j.ijpharm.2020.119046
    [8] 陈昊文, 陈淼鑫, 刘晔宏, 张钰华, 徐首红. pH/温度刺激响应型核-壳结构介孔二氧化硅纳米颗粒的设计与制备 [J]. 功能高分子学报,2022,35(2):155-163. doi: 10.14133/j.cnki.1008-9357.20210402001

    CHEN H W, CHEN M X, LIU Y H , ZHANG Y H, XU S H. Design and preparation of pH/temperature stimulated responsive core-shell mesoporous silica nanoparticles [J]. Journal of Functional Polymers,2022,35(2):155-163. doi: 10.14133/j.cnki.1008-9357.20210402001
    [9] POURJAVADI A, ASGARI S, HOSSEINI S H. Graphene oxide functionalized with oxygen-rich polymers as a pH-sensitive carrier for co-delivery of hydrophobic and hydrophilic drugs [J]. Journal of Drug Delivery Science and Technology,2020,56:101542. doi: 10.1016/j.jddst.2020.101542
    [10] ZHANG L, PU Y, LI J, YAN Q, GU Z, GAO W, HE B. pH responsive coumarin and imidazole grafted polymeric micelles for cancer therapy [J]. Journal of Drug Delivery Science and Technology,2020,58:101789. doi: 10.1016/j.jddst.2020.101789
    [11] DAI Y, LI Q, ZHANG S, SHI S, LI Y, ZHAO X, ZHOU L, WANG X, ZHU Y, LI W. Smart GSH/pH dual-bioresponsive degradable nanosponges based on β-CD-appended hyper-cross-linked polymer for triggered intracellular anticancer drug delivery [J]. Journal of Drug Delivery Science and Technology,2021,64:102650. doi: 10.1016/j.jddst.2021.102650
    [12] AGGARWAL V, TULI H S, VAROL A, THAKRAL F, YERER B, SAK K, VAROL M, JAIN A, KHAN A, SETHI G. Role of reactive oxygen species in cancer progression: Molecular mechanisms and recent advancements[J]. Biomolecules, 2019, 9(11):735.
    [13] PU X Q, JU X J, ZHANG L, CAI Q, LIU Y, PENG H, XIE R, WANG W, ZHUANG L, CHU L. Novel multifunctional stimuli-responsive nanoparticles for synergetic chemo-photothermal therapy of tumors [J]. ACS Appl Mater Interfaces,2021,13(24):28802-28817. doi: 10.1021/acsami.1c05330
    [14] XIONG D, ZHANG X, PENG S, GU H, ZHANG L. Smart pH-sensitive micelles based on redox degradable polymers as DOX/GNPs carriers for controlled drug release and CT imaging [J]. Colloids Surf B Biointerfaces,2018,163:29-40. doi: 10.1016/j.colsurfb.2017.12.008
    [15] GHEZZI M, PESCINA S, PADULA C, M, SANTI P, del FAVERO E L, CANTU B, NICOLI S. Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions [J]. J Control Release,2021,332:312-336. doi: 10.1016/j.jconrel.2021.02.031
    [16] WU D, XU S, ZHANG X, LI Y, ZHANG W, YAN Q, YANG Q, GUO F, YANG G. A near-infrared laser-triggered size-shrinkable nanosystem with in situ drug release for deep tumor penetration [J]. ACS Appl Mater Interfaces,2021,13(14):16036-16047. doi: 10.1021/acsami.1c00022
    [17] TANG S, MENG Q, SUN H, SUN J, YIN Q, ZHANG Z, YU H, CHEN L, GU W, LI Y. Dual pH-sensitive micelles with charge-switch for controlling cellular uptake and drug release to treat metastatic breast cancer [J]. Biomaterials,2017,114:44-53. doi: 10.1016/j.biomaterials.2016.06.005
    [18] FEI Z, YOOSEFIAN M. Design and development of polymeric micelles as nanocarriers for anti-cancer Ribociclib drug [J]. Journal of Molecular Liquids,2021,329:115574. doi: 10.1016/j.molliq.2021.115574
    [19] YANG H, KHAN A R, LIU M, FU M, JI J, CHI L, ZHAI G. Stimuli-responsive polymeric micelles for the delivery of paclitaxel [J]. Journal of Drug Delivery Science and Technology,2020,56:101523. doi: 10.1016/j.jddst.2020.101523
    [20] HAO W, HAN X, SHANG Y, XU S, LIU H. Insertion of pH-sensitive bola-type copolymer into liposome as a "stability anchor" for control of drug release [J]. Colloids Surf B Biointerfaces,2015,136:809-816. doi: 10.1016/j.colsurfb.2015.10.033
    [21] HAO W J, ZHANG J Q, SHANG Y Z, XU S, LIU H. Preparation of fluorescently labeled pH-sensitive micelles for controlled drug release [J]. Acta Physico-Chimica Sinica,2016,32(10):2628-2635. doi: 10.3866/PKU.WHXB201606296
    [22] LEI B, CHEN M, WANG Y, ZHANG J, XU S, LIU H. Double security drug delivery system DDS constructed by multi-responsive (pH/redox/US) microgel [J]. Colloids Surf B Biointerfaces,2020,193:111022. doi: 10.1016/j.colsurfb.2020.111022
    [23] WANG Y, LIU Y, XU S, LIU H. Design and synthesis of multi-responsive copolymers for drug carrier [J]. Acta Physico-Chimica Sinica,2019,35(8):876-884. doi: 10.3866/PKU.WHXB201901019
    [24] LEI B, SUN M, CHEN M, XU S, LIU H. pH and temperature double-switch hybrid micelles for controllable drug release [J]. Langmuir,2021,37(50):14628-14637. doi: 10.1021/acs.langmuir.1c02298
    [25] ZHAO C, DOLMANS L, ZHU X X. Thermoresponsive behavior of poly(acrylic acid-co-acrylonitrile) with a UCST [J]. Macromolecules,2019,52(12):4441-4446. doi: 10.1021/acs.macromol.9b00794
    [26] OTSUKA C, WAKAHARA Y, OKABE K, SAKATA J, OKUYAMA M, HAYASHI A, TOKUYAMA H, UCHIYAMA H. Fluorescent labeling method re-evaluates the intriguing thermoresponsive behavior of poly(acrylamide-co-acrylonitrile)s with upper critical solution temperatures [J]. Macromolecules,2019,52(20):7646-7660. doi: 10.1021/acs.macromol.9b00880
    [27] 吴春, 孔琪, 李健, 许威. 槲皮素微胶囊的稳定性及缓释性能研究 [J]. 化学与黏合,2006,28(1):11-13.

    WU C, KONG Q, LI J, XU W. Study on stability and controlled release of microencapsulating quercetin [J]. Chemistry and Adhesion,2006,28(1):11-13.
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出版历程
  • 收稿日期:  2022-03-22
  • 录用日期:  2022-07-07
  • 网络出版日期:  2022-10-17

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