高级搜索

金属有机框架在肿瘤治疗中的应用进展

郭阳, 吴素清, 温朝辉

郭阳, 吴素清, 温朝辉. 金属有机框架在肿瘤治疗中的应用进展[J]. 肿瘤防治研究, 2022, 49(5): 472-477. DOI: 10.3971/j.issn.1000-8578.2022.21.1158
引用本文: 郭阳, 吴素清, 温朝辉. 金属有机框架在肿瘤治疗中的应用进展[J]. 肿瘤防治研究, 2022, 49(5): 472-477. DOI: 10.3971/j.issn.1000-8578.2022.21.1158
GUO Yang, WU Suqing, WEN Zhaohui. Application Progress of Metal-organic Frameworks in Tumors Therapy[J]. Cancer Research on Prevention and Treatment, 2022, 49(5): 472-477. DOI: 10.3971/j.issn.1000-8578.2022.21.1158
Citation: GUO Yang, WU Suqing, WEN Zhaohui. Application Progress of Metal-organic Frameworks in Tumors Therapy[J]. Cancer Research on Prevention and Treatment, 2022, 49(5): 472-477. DOI: 10.3971/j.issn.1000-8578.2022.21.1158

金属有机框架在肿瘤治疗中的应用进展

基金项目: 

国家自然科学基金 51873052

详细信息
    作者简介:

    郭阳(1991-),男,硕士在读,主要从事超声诊断与纳米材料的研究

    通讯作者:

    温朝辉(1968-),女,博士,主任医师,主要从事超声诊断与纳米材料的研究,E-mail: wenzhaohui1968@163.com

  • 中图分类号: R730.8

Application Progress of Metal-organic Frameworks in Tumors Therapy

Funding: 

National Natural Science Foundation of China 51873052

More Information
  • 摘要:

    金属有机框架(MOFs)是一类由金属离子和有机配体通过配位反应自组装形成的特殊材料,具有生物相容性好、比表面积大、pH敏感度强等理化性质。进行修饰或改性后,可以制备出性能优良的复合纳米材料,在肿瘤治疗方面有着巨大的应用前景。本文主要基于MOFs及其衍生材料在肿瘤载药治疗、光动力治疗及免疫治疗中的应用进行综述。

     

    Abstract:

    Metal-organic frameworks (MOFs) are special materials formed by self-assembly of metal ions and organic ligands, with special physical and chemical properties, such as large specific surface area, excellent biocompatibility and strong pH sensitivity, etc. Through modification, they have synthesized nanomaterials with excellent performance, which have huge application prospects in treating tumors. This paper mainly reviews the properties of MOFs and their derived materials, and the application progress of MOFs in tumor drug-loaded therapy, photodynamic therapy and immunotherapy.

     

  • 神经纤毛蛋白1(Neuropilin-1, NRP-1)是一种多功能的跨膜糖蛋白,在生理和病理条件下都可作为多种生长因子或其他配体的共受体而发挥不同的生物学功能,在免疫、肿瘤、血管发育和神经等系统中发挥重要作用[1],前期研究表明NRP-1在乳腺癌、淋巴瘤、卵巢癌、黑色素瘤、胃肠道肿瘤等多种人类肿瘤组织及癌细胞株中均过表达,但在相应的正常组织中表达较低,并与肿瘤的预后相关,因此NRP-1在肿瘤的发生和发展中起重要作用[2-5]

    Treg细胞(CD4+CD25+CD127-Treg)是一群具有低反应性及免疫抑制功能的调节性T细胞,能阻断机体抗肿瘤免疫,达到肿瘤免疫逃逸,促进肿瘤发生、发展的作用[6]。树突状细胞(dendritic cell, DC)是一种抗原呈递细胞,目前人类外周血DC细胞主要分为髓样树突状细胞(myeloid dendritic cell, MDC)和浆细胞样树突状细胞(plasmacytdid dendritic cell, PDC)(CD123+CD303+CD304+)2个亚型,其中PDC在诱导抗原特异性抗肿瘤免疫反应上发挥重要作用[7]。但有关NRP-1与Treg、PDC在非小细胞肺癌方面的研究却鲜见报道,本研究检测了非小细胞肺癌患者和健康体检者外周血中NRP-1在Treg、PDC的表达,旨在探讨其在非小细胞肺癌发生中免疫调节的可能机制,并分析其与临床参数的相关性,为NSCLC病情监测、治疗策略、疗效判断及预后评估提供新的相关指标。

    收集2018年6月—2019年9月就诊于徐州医科大学附属医院的49例均经手术、纤维支气管镜或经皮肺穿刺活检确诊为非小细胞肺癌患者的外周血,具有完整的临床、影像学、病理及随访资料。前期均未接受针对癌症的治疗(化疗、放疗以及生物免疫治疗等),近3月内未使用过免疫增强剂。全部符合世界卫生组织(WHO)的诊断标准。49例非小细胞肺癌患者年龄30~74岁,中位年龄61岁。其中男32例、女17例。按2018年国际抗癌联盟TNM肺癌病理分期分为:Ⅰ期18例、Ⅱ12例、Ⅲ期11例、Ⅳ期8例。同时收集徐州医科大学附属医院33例健康体检者外周血作为对照组,年龄22~70岁,中位年龄55岁。其中男17例、女16例。本研究获得徐州医科大学伦理委员会批准。

    FITC/Alexa Fluor 488-A标记的抗人CD4单克隆抗体试剂、APC标记的抗人CD25单克隆抗体试剂、Alexa Fluor 700标记的抗人CD3单克隆抗体试剂及PE.Cy5标记的抗人CDl27单克隆抗体试剂均购自美国Biolegend公司;Brilliant Violet 421标记的抗人CD304(NRP-1)单克隆抗体试剂、PEcy7标记的抗人CD123单克隆抗体试剂、APC-Fire750标记的抗人CD303单克隆抗体试剂、libIlr流式细胞仪及percp-cy5.5标记的抗人CD45单克隆抗体试剂均购自美国BD公司。

    清晨空腹抽取外周静脉血2 ml(肝素抗凝),于2 h内检测。取200 μl静脉血于流式管中,加抗体2 μl混匀,暗处孵育20 min;加红细胞裂解液2 ml,混匀,充分裂解红细胞;加2 ml PBS混匀,2 000 r/min离心,洗涤3次,加200 μl PBS混匀,置暗处4℃待上机,流式细胞仪检测NRP-1的表达。

    用SPSS21.0软件对数据进行统计分析。计量资料经正态性检验,符合正态分布的数据均采用均数±标准差()表示,两组间比较采用独立样本t检验;多组间比较采用单因素方差分析,进一步采用LSD法对有统计学意义的指标进行两两比较。分类计数资料均采用例数(百分比)表示,组间比较采用χ2检验。检验水准均为P < 0.05有统计学意义。

    结果显示,肺癌患者外周血CD4+T表达为(34.19±7.61)%,Treg表达为(8.24±1.12)%,Treg上中NRP-1的表达为17.44±5.04;健康体检者外周血CD4+T表达为(38.91±4.85)%,Treg表达为(5.25±0.82)%,Treg中NRP-1的表达为12.69±3.29,见图 1

    图  1  肺癌患者(A)与健康体检者(B)外周血Treg细胞膜中NRP-l的表达流式图
    Figure  1  Flow cytometry of NRP-l expression in Treg cell membrane in peripheral blood of NSCLC patients(A) and healthy subjects(B)

    对照组外周血CD4+T、PDC的表达均明显高于非小细胞肺癌组,对照组外周血Treg/CD4+T表达与NRP-1的表达均明显低于非小细胞肺癌组(均P < 0.05),见表 1

    表  1  对照组和肺癌组临床指标比较(()
    Table  1  Comparison of clinical indicators between control group and NSCLC group ()
    下载: 导出CSV 
    | 显示表格

    49例NSCLC外周血中Treg/CD4+T表达情况与肿瘤最大径、有无淋巴结转移、TNM分期、分化程度有关,差异有统计学意义(P < 0.05)。随着TNM分期的升高和分化程度的降低,TregCD4+T的表达呈增高趋势,差异有统计学意义(P < 0.05),见表 2

    表  2  Treg/CD4+T、NRP-1与NSCLC患者临床病理参数之间的关系()
    Table  2  Correlation of Treg/CD4+T, NRP-1 with clinicopathological parameters of NSCLC patients (()
    下载: 导出CSV 
    | 显示表格

    49例NSCLC外周血Treg中NRP-1的表达情况与肿瘤最大径、有无淋巴结转移、TNM分期、分化程度有关,差异有统计学意义(P < 0.05),随着TNM分期的升高和分化程度的降低,NRP-1的表达呈增高趋势,差异有统计学意义(P < 0.05),见表 2

    49例NSCLC外周血PDC中NRP-1的表达情况与肿瘤最大径、有无淋巴结转移、TNM分期有关,差异有统计学意义(P < 0.05)。随着TNM分期的升高,NRP-1在PDC中的表达呈递减趋势,差异有统计学意义(P < 0.05),见表 3

    表  3  NRP-1在PDC中的表达与NSCLC患者临床病理参数之间的关系()
    Table  3  Relation between NRP-1 expression on PDC and clinicopathological parameters of NSCLC patients (()
    下载: 导出CSV 
    | 显示表格

    NSCLC患者Treg/CD4+T与NRP-1存在明显的正相关关系(r > 0, P < 0.05);Treg/CD4+T与PDC存在明显的负相关关系(r < 0, P < 0.05),见表 4

    表  4  Treg/CD4+T与CD4+T、NRP-1(Treg)、PDC的相关性分析
    Table  4  Correlation of Treg/CD4+T with CD4+T, NRP-1 (Treg) and PDC
    下载: 导出CSV 
    | 显示表格

    肺癌是全球癌症死亡的主要原因之一,死亡率在中国癌症相关死亡率中排名第一。最常见的病理类型是非小细胞肺癌(non-small cell lung cancer, NSCLC),主要包含鳞状细胞癌(SCC)、腺癌(LAC)和大细胞癌(LCC)[8]。随着精准医学的发展,化学治疗、放射治疗、靶向治疗以及免疫治疗虽然延长了一部分中晚期肺癌患者的生存期,然而5年生存率仍小于21%[9]。因此,寻找简便易操作的预后评估指标具有重要的临床意义。近年来,关于肺癌患者的免疫功能引起重视,研究表明恶性肿瘤的发生、发展、转移和复发与机体的免疫功能缺陷有关,肺癌患者存在一定程度的免疫功能异常。随着对肺癌免疫耐受机制的深入研究,CD4+T、NRP-1、Treg以及PDC在肺癌发生、发展中的相互作用日益引起国内外学者的关注。

    T淋巴细胞亚群的主要作用是调节机体免疫系统,在正常机体内各T细胞亚群保持动态平衡,维持机体正常细胞免疫应答。当T淋巴细胞亚群比例出现异常时,杀伤肿瘤细胞、控制肿瘤生长的作用明显减低[10]。CD3+代表总T细胞,主要分为CD4+、CD8+T细胞两大亚群,本研究检测CD4+T(CD3+CD4+T)在非小细胞肺癌患者和健康体检者的细胞比率,结果显示非小细胞肺癌患者CD4+T细胞比率明显低于健康体检者,可能原因是肿瘤细胞诱导抑制性免疫微环境的形成。临床上可通过检测肿瘤患者外周血中T淋巴细胞亚群的变化来进一步评估患者免疫功能状态和病情变化,可指导临床使用免疫调节剂及其他药物。

    目前国内外大多数学者认为NRP-1是VEGF165高亲和力受体,NRP-1通过NRP-1b1/b2结构域与络氨酸激酶受体VEGFR2结合,促进肿瘤血管的生成,在肿瘤细胞增殖、黏附、迁移、侵袭中都发挥重要作用,并且与肿瘤的发生、发展、转移、复发有关[1]。Treg是一群具有独特免疫负性调节功能的细胞,不但可抑制自身免疫性疾病的发生,而且还参与肿瘤的免疫调节[11]。近年来癌症患者肿瘤组织及外周血中Treg的积累已被广泛研究,并且与癌症进展、肿瘤免疫逃逸、预后差和对治疗缺乏反应有关。但迄今为止国内外研究中鲜见NRP-1和Treg两者在非小细胞肺癌中表达的相关研究。本研究同时检测了NRP-1和Treg两者在非小细胞肺癌中表达的情况。结果发现,两者在非小细胞肺癌表达明显高于健康体检者,随着肺癌TNM分期的升高和分化程度的降低,NRP-l、Treg的表达呈明显递增趋势。而且,相关性分析发现外周血中NRP-1表达与Treg细胞比率呈正相关(r > 0, P < 0.05)。NRP-1在癌症患者外周血Treg中的表达上调。动物实验已经证明,NRP-1与Treg介导的肿瘤免疫逃逸机制有关,NRP-1充当VEGF的共受体,并已被证明在肿瘤的Treg浸润中起重要作用,通过在Treg中表达的NRP-1起作用,肿瘤衍生的VEGF吸引NRP-1+Treg进入肿瘤组织[12],增强肿瘤的免疫逃逸,从而促进肿瘤的发生和发展。

    在人外周血中,NRP-1在PDC细胞上高表达,当前有许多标记用于识别PDC,包括CD123、BDCA-2(CD303)和NRP1(CD304)。研究表明NRP-1可通过与肿瘤细胞衍生出的VEGF的相互作用而参与PDC的肿瘤浸润,而Treg则可通过与NRP-1的相互作用,弱化DC活化效应性T细胞的功能,最终使效应性淋巴细胞活化不足,抗肿瘤抗原效应减弱[1]。本实验数据提示非小细胞肺癌外周血Treg与PDC呈明显负相关(r < 0, P < 0.05)。近年来,程序性死亡受体1(programmed death 1, PD-1)/程序性死亡配体1(programmed death ligand 1, PD-L1)免疫检查点抑制剂成为肺癌免疫治疗研究热点,PD-1在活化后的CD8+T、CD4+T、B、DC及单核细胞等诸多免疫细胞上表达[13-14]。胸腺来源的Treg细胞(tTreg)可表达PD-1。PD-1/PD-L1相互作用有助于使CD4+T细胞转化成Treg细胞,Treg细胞上表达的PD-1还可以与T细胞上表达的PD-L1相互作用,以介导免疫抑制,在抗原识别过程中,NRP-1表达促进Treg与DC的相互作用,从而抑制T细胞活化[15]。但非小细胞肺癌患者外周血中NRP-1与Treg、PDC、PD-1相互作用的具体机制,相关文献报道较少,因此明确其相互作用的关系可能有利于对非小细胞肺癌免疫治疗。

    NRP-1在人外周血Treg、PDC细胞表达的研究结果有显著差异,提示NRP-1通过与Treg、PDC的广泛相互作用在免疫调节和功能中起着重要作用。但NRP-1与Treg、PDC之间的作用机制有待进一步研究,从而使抗NRP-1治疗成为肿瘤治疗的新靶点和途径,为临床寻找新的治疗方法提供理论依据。

    Competing interests: The authors declare that they have no competing interests.
    作者贡献:
    郭阳:检索文献及撰写论文
    吴素清:修改文章
    温朝辉:指导选题及修改文章
  • [1]

    Zhang H, Jiang W, Liu R, et al. Rational Design of Metal Organic Framework Nanocarrier-Based Codelivery System of Doxorubicin Hydrochloride/Verapamil Hydrochloride for Overcoming Multidrug Resistance with Efficient Targeted Cancer Therapy[J]. ACS Appl Mater Interfaces, 2017, 9(23): 19687-19697. doi: 10.1021/acsami.7b05142

    [2]

    Song J, Huang Z, Mao J, et al. A facile synthesis of uniform hollow MIL-125 titanium-based nanoplatform for endosomal esacpe and intracellular drug delivery[J]. Chem Eng J, 2020, 396: 125246. doi: 10.1016/j.cej.2020.125246

    [3]

    Hu WC, Younis MR, Zhou Y, et al. In Situ Fabrication of Ultrasmall Gold Nanoparticles/2D MOFs Hybrid as Nanozyme for Antibacterial Therapy[J]. Small, 2020, 16(23): e2000553. doi: 10.1002/smll.202000553

    [4]

    Wang D, Zhao C, Gao G, et al. Multifunctional NaLnF4@MOF-Ln Nanocomposites with Dual-Mode Luminescence for Drug Delivery and Cell Imaging[J]. Nanomaterials (Basel), 2019, 9(9): 1274. doi: 10.3390/nano9091274

    [5]

    Gao S, Zheng P, Li Z, et al. Biomimetic O2-Evolving metal-organic framework nanoplatform for highly efficient photodynamic therapy against hypoxic tumor[J]. Biomaterials, 2018, 178: 83-94. doi: 10.1016/j.biomaterials.2018.06.007

    [6]

    Farha OK, Eryazici I, Jeong NC, et al. Metal-organic framework materials with ultrahigh surface areas: is the sky the limit?[J]. J Am Chem Soc, 2012, 134(36): 15016-15021. doi: 10.1021/ja3055639

    [7]

    Wu Z, Hao N, Zhang H, et al. Mesoporous iron-carboxylate metal-organic frameworks synthesized by the double-template method as a nanocarrier platform for intratumoral drug delivery[J]. Biomater Sci, 2017, 5(5): 1032-1040. doi: 10.1039/C7BM00028F

    [8]

    Li L, Han S, Yang C, et al. Glycyrrhetinic acid modified MOFs for the treatment of liver cancer[J]. Nanotechnology, 2020, 31(32): 325602. doi: 10.1088/1361-6528/ab8c03

    [9]

    Pandey A, Kulkarni S, Vincent AP, et al. Hyaluronic acid-drug conjugate modified core-shell MOFs as pH responsive nanoplatform for multimodal therapy of glioblastoma[J]. Int J Pharm, 2020, 588: 119735. doi: 10.1016/j.ijpharm.2020.119735

    [10]

    Kan J, Jiang Y, Xue A, et al. Surface Decorated Porphyrinic Nanoscale Metal–Organic Framework for Photodynamic Therapy[J]. Inorg Chem, 2018, 57(9): 5420-5428. doi: 10.1021/acs.inorgchem.8b00384

    [11]

    Lan G, Ni K, Xu Z, et al. Nanoscale Metal-Organic Framework Overcomes Hypoxia for Photodynamic Therapy Primed Cancer Immunotherapy[J]. J Am Chem Soc, 2018, 140(17): 5670-5673. doi: 10.1021/jacs.8b01072

    [12]

    He T, Ni B, Zhang S, et al. Ultrathin 2D Zirconium Metal-Organic Framework Nanosheets: Preparation and Application in Photocatalysis[J]. Small, 2018, 14(16): e1703929. doi: 10.1002/smll.201703929

    [13]

    Shahrak MN, Ghahramaninezhad M, Eydifarash M. Zeolitic imidazolate framework-8 for efficient adsorption and removal of Cr(VI) ions from aqueous solution[J]. Environ Sci Pollut Res Int, 2017, 24(10): 9624-9634. doi: 10.1007/s11356-017-8577-5

    [14]

    Zou Y, Liu X, Zhang H. A dual enzyme-containing microreactor for consecutive digestion based on hydrophilic ZIF-90 with size-selective sheltering[J]. Colloids Surf B Biointerfaces, 2021, 197: 111422. doi: 10.1016/j.colsurfb.2020.111422

    [15]

    Tang XQ, Zhang YD, Jiang ZW, et al. Fe3O4 and metal-organic framework MIL-101(Fe) composites catalyze luminol chemiluminescence for sensitively sensing hydrogen peroxide and glucose[J]. Talanta, 2018, 179: 43-50. doi: 10.1016/j.talanta.2017.10.049

    [16]

    Li B, Wang X, Chen L, et al. Ultrathin Cu-TCPP MOF nanosheets: a new theragnostic nanoplatform with magnetic resonance/near-infrared thermal imaging for synergistic phototherapy of cancers[J]. Theranostics, 2018, 8(15): 4086-4096. doi: 10.7150/thno.25433

    [17]

    Lo WS, Liu SM, Wang SC, et al. A green and facile approach to obtain 100 nm zeolitic imidazolate framework-90 (ZIF-90) particles via leveraging viscosity effects[J]. RSC Adv, 2014, 4(95): 52883-52886. doi: 10.1039/C4RA10488A

    [18]

    Jones CG, Stavila V, Conroy MA, et al. Versatile Synthesis and Fluorescent Labeling of ZIF-90 Nanoparticles for Biomedical Applications[J]. ACS Appl Mater Interfaces, 2016, 8(12): 7623-7630. doi: 10.1021/acsami.5b11760

    [19]

    Torad NL, Hu M, Kamachi Y, et al. Facile synthesis of nanoporous carbons with controlled particle sizes by direct carbonization of monodispersed ZIF-8 crystals[J]. Chem Commun (Camb), 2013, 49(25): 2521-2523. doi: 10.1039/c3cc38955c

    [20]

    Nejadshafiee V, Naeimi H, Goliaei B, et al. Magnetic bio-metal-organic framework nanocomposites decorated with folic acid conjugated chitosan as a promising biocompatible targeted theranostic system for cancer treatment[J]. Mater Sci Eng C Mater Biol Appl, 2019, 99: 805-815. doi: 10.1016/j.msec.2019.02.017

    [21]

    Horcajada P, Gref R, Baati T, et al. Metal-Organic Frameworks in Biomedicine[J]. Chem Rev, 2012, 112(2): 1232-1268. doi: 10.1021/cr200256v

    [22]

    PandeyA, Kulkarni S, Vincent AP, et al. Hyaluronic Acid-Drug Conjugate Modified Core-Shell MOFs as pH Responsive Nanoplatform for Multimodal Therapy of Glioblastoma[J]. Int J Pharm, 2020, 588: 119735. doi: 10.1016/j.ijpharm.2020.119735

    [23]

    He Y, Zhang W, Guo T, et al. Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan[J]. Acta Pharm Sin B, 2019, 9(1): 97-106. doi: 10.1016/j.apsb.2018.09.003

    [24]

    Fernández-Paz C, Rojas S, Salcedo-Abraira P, et al. Metal-Organic Framework Microsphere Formulation for Pulmonary Administration[J]. ACS Appl Mater Interfaces, 2020, 12(23): 25676-25682. doi: 10.1021/acsami.0c07356

    [25]

    Tan G, Zhong Y, Yang L, et al. A multifunctional MOF-based nanohybrid as injectable implant platform for drug synergistic oral cancer therapy[J]. Chem Eng J, 2020, 390(2018): 124446.

    [26]

    Liang W, Xu H, Carraro F, et al. Enhanced Activity of Enzymes Encapsulated in Hydrophilic Metal-Organic Frameworks[J]. J Am Chem Soc, 2019, 141(6): 2348-2355. doi: 10.1021/jacs.8b10302

    [27]

    Rahmati Z, Abdi J, Vossoughi M, et al. Ag-doped magnetic metal organic framework as a novel nanostructured material for highly efficient antibacterial activity[J]. Environ Res, 2020, 188: 109555. doi: 10.1016/j.envres.2020.109555

    [28]

    Shen M, Forghani F, Kong X, et al. Antibacterial applications of metal-organic frameworks and their composites[J]. Compr Rev Food Sci Food Saf, 2019, 19(4): 1397-1419.

    [29]

    Wang XG, Xu L, Li MJ, et al. Construction of Flexible-on-Rigid Hybrid-Phase Metal-Organic Frameworks (MOFs) for Controllable Multi-Drug Delivery[J]. Angew Chem Int Ed Engl, 2020, 59(41): 18078-18086. doi: 10.1002/anie.202008858

    [30]

    Chen G, Huang S, Kou X, et al. Embedding Functional Biomacromolecules within Peptide-Directed Metal-Organic Framework (MOF) Nanoarchitectures Enables Activity Enhancement[J]. Angew Chem Int Ed Engl, 2020, 59(33): 13947-13954. doi: 10.1002/anie.202005529

    [31]

    Liao FS, Lo WS, Hsu YS, et al. Shielding against Unfolding by Embedding Enzymes in Metal-Organic Frameworks via ade Novo Approach[J]. J Am Chem Soc, 2017, 139(19): 6530-6533. doi: 10.1021/jacs.7b01794

    [32]

    Huang S, Kou X, Shen J, et al. "Armor-Plating" Enzymes with Metal-Organic Frameworks (MOFs)[J]. Angew Chem Int Ed Engl, 2020, 59(23): 8786-8798. doi: 10.1002/anie.201916474

    [33]

    Chen Y, Lykourinou V, Vetromile C, et al. How Can Proteins Enter the Interior of a MOF? Investigation of Cytochromec Translocation into a MOF Consisting of Mesoporous Cages with Microporous Windows[J]. J Am Chem Soc, 2012, 134(32): 13188-13191. doi: 10.1021/ja305144x

    [34]

    An J, Hu YG, Li C, et al. A pH/Ultrasound dual-response biomimetic nanoplatform for nitric oxide gas-sonodynamic combined therapy and repeated ultrasound for relieving hypoxia[J]. Biomaterials, 2020, 230: 119636. doi: 10.1016/j.biomaterials.2019.119636

    [35]

    Park J, Jiang Q, Feng D, et al. Size-Controlled Synthesis of Porphyrinic Metal-Organic Framework and Functionalization for Targeted Photodynamic Therapy[J]. J Am Chem Soc, 2016, 138(10): 3518-3525. doi: 10.1021/jacs.6b00007

    [36]

    Xu W, Qian J, Hou G, et al. A dual-targeted hyaluronic acid-gold nanorod platform with triple-stimuli responsiveness for photodynamic/photothermal therapy of breast cancer[J]. Acta Biomater, 2019, 83: 400-413. doi: 10.1016/j.actbio.2018.11.026

    [37]

    Cai Z, Xin F, Wei Z, et al. Photodynamic Therapy Combined with Antihypoxic Signaling and CpG Adjuvant as an In Situ Tumor Vaccine Based on Metal-Organic Framework Nanoparticles to Boost Cancer Immunotherapy[J]. Adv Healthc Mater, 2019, 9(1): e1900996.

    [38]

    Zhao J, Lu D, Moya SE, et al. Bispecific T-cell engager (BiTE) immunotherapy of ovarian cancer based on MIL-88A MOF/MC gene delivery system[J]. Appl Mater Today, 2020, 20(2): 100701.

    [39]

    Shao Y, Liu B, Di Z, et al. Engineering of Upconverted Metal-Organic Frameworks for Near-Infrared Light-Triggered Combinational Photodynamic/Chemo-/Immunotherapy against Hypoxic Tumors[J]. J Am Chem Soc, 2020, 142(8): 3939-3946. doi: 10.1021/jacs.9b12788

    [40]

    Miao YB, Pan WY, Chen KH, et al. Engineering a Nanoscale Al-MOF-Armored Antigen Carried by a "Trojan Horse"-Like Platform for Oral Vaccination to Induce Potent and Long-Lasting Immunity[J]. Adv Funct Mater, 2019, 29(43): 1904828. doi: 10.1002/adfm.201904828

计量
  • 文章访问数:  1557
  • HTML全文浏览量:  448
  • PDF下载量:  1326
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-10-13
  • 修回日期:  2021-11-28
  • 网络出版日期:  2024-01-12
  • 刊出日期:  2022-05-24

目录

/

返回文章
返回
x 关闭 永久关闭