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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

陈昊文 陈淼鑫 刘晔宏 张钰华 徐首红

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. doi: 10.14133/j.cnki.1008-9357.20210402001
引用本文: 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. doi: 10.14133/j.cnki.1008-9357.20210402001
CHEN Haowen, CHEN Miaoxin, LIU Yehong, ZHANG Yuhua, XU Shouhong. Design and Preparation of pH/Temperature Stimulated Responsive Core-Shell Mesoporous Silica Nanoparticles[J]. Journal of Functional Polymers. doi: 10.14133/j.cnki.1008-9357.20210402001
Citation: CHEN Haowen, CHEN Miaoxin, LIU Yehong, ZHANG Yuhua, XU Shouhong. Design and Preparation of pH/Temperature Stimulated Responsive Core-Shell Mesoporous Silica Nanoparticles[J]. Journal of Functional Polymers. doi: 10.14133/j.cnki.1008-9357.20210402001

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

doi: 10.14133/j.cnki.1008-9357.20210402001
基金项目: 国家自然科学基金项目(21776071,22078087)
详细信息
    作者简介:

    陈昊文(1996—),男,硕士生,研究方向为智能药物载体设计与合成。E-mail:648429247@qq.com

    通讯作者:

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

  • 中图分类号: O648.2

Design and Preparation of pH/Temperature Stimulated Responsive Core-Shell Mesoporous Silica Nanoparticles

  • 摘要: 将具有pH敏感特性的聚合物聚甲基丙烯酸二异丙胺基乙酯(PDPA)和靶向分子叶酸(FA)接枝到介孔二氧化硅纳米颗粒(MSNs)表面,合成了MSNs-PDPA-FA。然后将单体甲基-2-丙烯酸-2-(2-甲氧基乙氧基)乙酯(MEO2MA)、聚乙二醇甲醚甲基丙烯酸酯(OEGMA)与甲基丙烯酸二异丙胺基乙酯(DPA)通过原子转移自由基聚合(ATRP)反应制备了pH/温度双重响应型聚合物P(MEO2MA90-co-OEGMA10)-b-PDPA10。最后在pH=7.4的条件下将聚合物P(MEO2MA90-co- OEGMA10)-b-PDPA10通过疏水作用自组装到MSNs-PDPA-FA的壳层来保护FA分子。通过粒径与透射率表征分析了该自组装体的pH/温度响应性能。并对该自组装纳米载体的体外释药动力学进行了研究。结果表明,该自组装体系能够灵敏地响应环境中pH与温度的变化。在正常生理环境下,48 h后的药物累计释放量不超过10%,而在pH=5.0、44 °C下,药物48 h的累计释放量达到65%。

     

  • 图  1  MSNs的聚合物修饰及其pH响应药物释放行为示意图

    Figure  1.  Schematic diagram of polymer modification and the pH-responsive drug release behavior of MSNs

    图  2  样品的 (a) 红外光谱图和(b) Zeta电位图

    Figure  2.  (a) FT-IR spectrum and (b) Zeta potential values of samples

    图  3  MSNs-PDPA-FA在不同pH下的(a)粒径分布曲线和(b)平均粒径变化曲线

    Figure  3.  (a) Particle size distribution and (b) average particle size of MSNs-PDPA-FA at different pH values

    图  4  P(MEO2MA90-co-OEGMA10)-b-PDPA10在CDCl3中的1H-NMR谱图

    Figure  4.  1H-NMR spectrum of P(MEO2MA90-co-OEGMA10)-b-PDPA10 in CDCl3

    图  5  P(MEO2MA90-co-OEGMA10)-b-PDPA10水溶液透射率与 (a)温度和(b) pH的变化关系

    Figure  5.  Transmittance of P(MEO2MA90-co-OEGMA10)-b-PDPA10 solution as a function of (a) temperature and (b) pH

    图  6  样品的(a)TEM图;(b)DLS粒径分布;(c) N2吸附-脱附曲线;(d) 孔径分布曲线

    1*—MSNs; 2*—MSNs— ···; 3*— ···

    Figure  6.  (a—c) TEM images; (b) size distribution; (c) nitrogen absorption-desorption isotherms and (d) pore size distributions of samples

    图  7  样品的热重分析曲线

    Figure  7.  TGA curves of samples

    图  8  MSNs-PDPA-FA@Polymer的粒径与温度的变化关系

    Figure  8.  The size of MSNs-PDPA-FA@Polymer as a function of temperature

    图  9  25 ℃下MSNs-PDPA-FA@Polymer的Zeta电位与pH的变化关系

    Figure  9.  Zeta potential values of MSNs-PDPA-FA@Polymer as a function of pH at 25 ℃

    图  10  MSNs-PDPA-FA@Polymer的(a)释药动力学曲线和(b)多阶段pH响应释药(44 ℃)

    Figure  10.  (a) Drug release kinetics curves and (b) the programmable drug release curves of MSNs-PDPA-FA@Polymer at 44 ℃

  • [1] ULBRICH K, HOLA K, SUBR V, et al. Targeted drug delivery with polymers and magnetic nanoparticles: Covalent and noncovalent approaches, release control, and clinical studies [J]. Chem Rev,2016,116(9):5338-5431. doi: 10.1021/acs.chemrev.5b00589
    [2] JIN Q, DENG Y, CHEN X, et al. Rational design of cancer nanomedicine for simultaneous stealth surface and enhanced cellular uptake [J]. ACS Nano,2019,13(9):954-977.
    [3] SURNAR B, SHARMA K, JAYAKANNAN M. Core-shell polymer nanoparticles for prevention of GSH drug detoxification and cisplatin delivery to breast cancer cells [J]. Nanoscale,2015,7(42):17964-17979. doi: 10.1039/C5NR04963F
    [4] HARTSHORN C M, BRADBURY M S, LANZA G M, et al. Nanotechnology strategies to advance outcomes in clinical cancer care [J]. ACS Nano,2018,12(1):24-43. doi: 10.1021/acsnano.7b05108
    [5] WANG J, WANG Y, LIU Q, et al. Rational design of multifunctional dendritic mesoporous silica nanoparticles to load curcumin and enhance efficacy for breast cancer therapy [J]. ACS Appl Mater Interfaces,2016,8(40):26511-26523. doi: 10.1021/acsami.6b08400
    [6] CHEN W, ZHOU S, GE L, et al. Translatable high drug loading drug delivery systems based on biocompatible polymer nanocarriers [J]. Biomacromolecules,2018,19(6):1732-1745. doi: 10.1021/acs.biomac.8b00218
    [7] ZHAO X, LIU P. Reduction-responsive core-shell-corona micelles based on triblock copolymers: Novel synthetic strategy, characterization, and application as a tumor microenvironment-responsive drug delivery system [J]. ACS Appl Mater Interfaces,2015,7(1):166-174. doi: 10.1021/am505531e
    [8] LAI W F, WONG W T, ROGACH A L. Molecular design of layer-by-layer functionalized liposomes for oral drug delivery [J]. ACS Appl Mater Interfaces,2020,12(39):43341-43351. doi: 10.1021/acsami.0c13504
    [9] YANG J, ZHANG Q, CHANG H, et al. Surface-engineered dendrimers in gene delivery [J]. Chem Rev,2015,115(11):5274-5300. doi: 10.1021/cr500542t
    [10] SHIAO Y S, CHIU H H, WU P H, et al. Aptamer-functionalized gold nanoparticles as photoresponsive nanoplatform for co-drug delivery [J]. ACS Appl Mater Interfaces,2014,6(24):21832-21841. doi: 10.1021/am5026243
    [11] WEN J, YANG K, LIU F, et al. Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems [J]. Chem Soc Rev,2017,46(19):6024-6045. doi: 10.1039/C7CS00219J
    [12] LIU J, DETREMBLEUR C, de PAUW-GILLET M C, et al. Gold nanorods coated with mesoporous silica shell as drug delivery system for remote near infrared light-activated release and potential phototherapy [J]. Small,2015,11(19):2323-2332. doi: 10.1002/smll.201402145
    [13] KAMALY N, YAMEEN B, WU J, et al. Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release [J]. Chem Rev,2016,116(4):2602-2663. doi: 10.1021/acs.chemrev.5b00346
    [14] CHENG Y J, QIN S Y, MA Y H, et al. Super-pH-sensitive mesoporous silica nanoparticle-based drug delivery system for effective combination cancer therapy [J]. ACS Biomater Sci Eng,2019,5(4):1878-1886. doi: 10.1021/acsbiomaterials.9b00099
    [15] MUHAMMAD F, GUO M, QI W, et al. pH-Triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids [J]. J Am Chem Soc,2011,133(23):8778-8781. doi: 10.1021/ja200328s
    [16] CHENG W, NIE J, XU L, et al. pH-Sensitive delivery vehicle based on folic acid-conjugated polydopamine-modified mesoporous silica nanoparticles for targeted cancer therapy [J]. ACS Appl Mater Interfaces,2017,9(22):18462-18473. doi: 10.1021/acsami.7b02457
    [17] CHANG B, CHEN D, WANG Y, et al. Bioresponsive controlled drug release based on mesoporous silica nanoparticles coated with reductively sheddable polymer shell [J]. Chemistry of Materials,2013,25(4):574-585. doi: 10.1021/cm3037197
    [18] ZHANG J, YUAN Z F, WANG Y, et al. Multifunctional envelope-type mesoporous silica nanoparticles for tumor-triggered targeting drug delivery [J]. Journal of the American Chemical Society,2013,135(13):5068-5073. doi: 10.1021/ja312004m
    [19] FENG Y, LI N X, YIN H L, et al. A thermo- and pH-responsive, lipid-coated, mesoporous silica nanoparticles-based dual drug delivery system to improve the anti-tumor effect of hydrophobic drugs. [J]. Mol Pharm,2019,16(1):422-436. doi: 10.1021/acs.molpharmaceut.8b01073
    [20] BAEK S, SINGH R K, KIM T H, et al. Triple hit with drug carriers: pH- and temperature-responsive theranostics for multimodal chemo- and photothermal therapy and diagnostic applications [J]. ACS Appl Mater Interfaces,2016,8(14):8967-8979. doi: 10.1021/acsami.6b00963
    [21] PARIS J L, VILLAVERDE G, CABANAS M V, et al. From proof-of-concept material to PEGylated and modularly targeted ultrasound-responsive mesoporous silica nanoparticles [J]. J Mater Chem B,2018,6(18):2785-2794. doi: 10.1039/C8TB00444G
    [22] LI X, XIE C, XIA H, et al. pH and Ultrasound dual-responsive polydopamine-coated mesoporous silica nanoparticles for controlled drug delivery [J]. Langmuir,2018,34(34):9974-9981. doi: 10.1021/acs.langmuir.8b01091
    [23] YANG K, LUO H, ZENG M, et al. Intracellular pH-triggered, targeted drug delivery to cancer cells by multifunctional envelope-type mesoporous silica nanocontainers [J]. ACS Appl Mater Interfaces,2015,7(31):17399-17407. doi: 10.1021/acsami.5b04684
    [24] CHENG Y J, ZHANG A Q, HU J J, et al. Multifunctional peptide-amphiphile end-capped mesoporous silica nanoparticles for tumor targeting drug delivery [J]. ACS Appl Mater Interfaces,2017,9(3):2093-2103. doi: 10.1021/acsami.6b12647
    [25] PECHAR M, POLA R, LAGA R, et al. Coiled coil peptides and polymer-peptide conjugates: Synthesis, self-assembly, characterization and potential in drug delivery systems [J]. Biomacromolecules,2014,15(7):2590-2599. doi: 10.1021/bm500436p
    [26] WANG Y, LIU Y, XU S, et al. 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
    [27] LI H J, DU J Z, LIU J, et al. 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
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出版历程
  • 收稿日期:  2021-04-02
  • 网络出版日期:  2021-05-06

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