English
往期目录
新闻公告
More
化学进展 2021, Vol. 33 Issue (5): 883-894 DOI: 10.7536/PC200660 前一篇   

• 研究论文 •

基于微/纳马达的智能癌症诊断、递送及治疗

王佳佳1, 吴惠英1, 董任峰1, 蔡跃鹏1   

  1. 1 华南师范大学化学学院 广州 510006
  • 收稿日期:2020-06-22 修回日期:2020-07-22 出版日期:2021-05-20 发布日期:2020-08-20
  • 基金资助:
    国家自然科学基金项目(21671071); 国家自然科学基金项目(21805096); 广东省科技计划项目(2017B090917002); 广东省科技计划项目(2019A050510038); 广东省科技计划项目(2019B1515120027); 中国博士后科学基金面上资助(2019M662948); 华南师范大学青年教师科研培育基金项目(18KJ13)
Richhtml ( 28 ) 下载PDF ( 444 ) 引用
导出

Micro/Nanomotors on the Way to Intelligent Cancer Diagnosis, Delivery and Therapy

Jiajia Wang1, Huiying Wu1, Renfeng Dong1, Yuepeng Cai1   

  1. 1 South China Normal University, School of Chemistry, Guangzhou 510006, China
  • Received:2020-06-22 Revised:2020-07-22 Online:2021-05-20 Published:2020-08-20
  • Supported by:
    National Natural Science Foundation of China(21671071); National Natural Science Foundation of China(21805096); Guangdong Provincial Science and Technology Project(2017B090917002); Guangdong Provincial Science and Technology Project(2019A050510038); Guangdong Provincial Science and Technology Project(2019B1515120027); China Postdoctoral Science Foundation(2019M662948); South China Normal University Young Teachers Research and Development Fund(18KJ13)

癌症严重威胁着人类的生命健康,早期的诊断和治疗对于提高癌症治愈率、挽救人们的生命有着至关重要的作用。随着纳米科技的发展,具有自主运动性能的微/纳马达为癌症的诊断与治疗带来了新的发展契机。微/纳马达能够有效地将多种能量(光、声、磁、电、热等)转化为自身运动的动能,有望在微米或纳米空间内执行各种复杂而精确的任务,这在智能化癌症诊疗领域具有得天独厚的优势。目前,已成功制备出不同形状的微/纳马达,比如线状马达、微管马达、Janus双面神结构马达等,促进了一系列新型诊断方法、胞内递送系统及光治疗策略等的发展。本文主要总结了微/纳马达在智能化癌症诊疗领域的研究进展,首先从化学场驱动与物理场驱动这两个角度总结了微/纳马达在检测和靶向递送方面的最新研究进展,并进一步总结了微/纳马达在癌症光治疗领域的应用进展,最后探讨了目前存在的问题及未来的发展方向。

关键词： 微/纳马达, 癌症, 诊断, 治疗, 智能化

Cancers seriously threaten human health due to their relatively high mortality. Early diagnosis and treatment play key roles in improving the cancers cure rate and saving people’s lives. With the development of science and nanotechnology, the advent of micro/nanomotors with self-propelled capabilities has enabled exciting opportunities for the diagnosis and therapy of cancers. The micro/nanomotors can effectively convert diverse energy sources(light, ultrasound, magnetic, electrical, heat, etc.) into their own driving forces, and show encouraging potential for performing various complex and precise tasks in the micrometer or nanometer space. Compared with nanomaterials with passive Brownian motion, micro/nanomotors with active propulsion capabilities endow more flexibility in intelligent cancer diagnosis and treatment. With the development of fabrication strategies, various shapes of micro/nanomotors that can be driven in various modes have been successfully fabricated, such as Janus microspheres, microtubular microrockets and nanowires, etc. These micro/nanomotors have been widely used in different fields of cancer research, as evidenced by significant breakthroughs in the development of a series of intracellular delivery systems, novel diagnosis methods and imaging strategies. In this review, we mainly focus on the tremendous inspiration and opportunities offered by micro/nanomotors in intelligent cancer diagnosis and therapy. Firstly, we demonstrate the recent progress of micro/nanomotors in the fields of cancer diagnostics(ranging from isolation of circulating tumor cells to detection of cancer related biomarkers, such as protein and microRNA), cancer-target delivery(such as drug, interfering RNA, etc.), as well as tumor phototherapy. The challenges and outlooks of micro/nanomotors for future development are also discussed.

Contents

1 Introduction

2 Cancer diagnosis

2.1 Chemical field-driven micro/nanomotor for detection of circulating tumor cells(CTC)

2.2 Physical field-driven micro/nanomotor for detection of intracellular tumor-related biomarkers

3 Targeted drug delivery

3.1 Chemical field-driven motor assist targeted drug delivery

3.2 Physical field-driven motor assist targeted drug delivery

4 Micro/nanomotor-assisted tumor phototherapy

4.1 Photothermal therapy of tumor

4.2 Photodynamic therapy of tumor

5 Conclusion and outlook

Key words: micro/nanomotors, cancer, diagnosis, therapy, intelligent
()
图1 (a) 用于捕获和分离循环肿瘤细胞的磁性纳米球[41];(b) 气泡驱动的微管马达用于捕获和分离癌细胞的过程示意图[42]
Fig. 1 (a) Magnetic nanospheres for capturing and separating circulating cancer cells[41];(b) Schematic illustration of microrockets for capture and isolation of cancer cells[42]
图2 超声驱动的FAM-AIB1-apt-GO/AuNW纳米马达基于“OFF-ON”荧光传感策略实现癌细胞中AIB1蛋白检测的示意图[59]
Fig. 2 Schematic diagram of AIB1 detection in living cancer cells using ultrasound(US)-propelled FAM-AIB1-apt-GO/AuNW nanomotors based on “OFF-ON” fluorescence sensing strategy [59]
图3 气泡驱动的Janus Pt/CaCO3@HA-CB[6]纳米马达通过双重刺激响应的靶向作用实现胞内递送的示意图[67]
Fig. 3 Schematic diagram of the intracellular delivery using Janus Pt/CaCO3@HA-CB[6] nanomotors by the dual stimuli-responsive targeting effect[67]
图4 (a) 基于介孔二氧化硅纳米粒子的脲酶催化纳米马达制备过程示意图[73];(b) 脲酶催化纳米马达应用于药物靶向递送的原理示意图;该马达以脲酶催化尿素为动力,超分子阀门在癌细胞的酸性环境下打开并释放马达所负载的药物[73]
Fig. 4 (a) Schematic illustration of the fabrication of enzyme-powered mesoporous silica nanomotors[73];(b) Schematic of enzyme-powered nanomotors for drug delivery;the nanomotors are driven by the enzymatic conversion of urea; at acidic pH in cancer cells, supramolecular nanovalve opens and releases their cargo[73]
图5 (a) 用于药物靶向递送的磁场驱动纳米马达结构示意图[39];(b) 精子混合马达用于药物靶向递送;负载有抗癌药物的精子混和马达在磁场引导下到达肿瘤细胞表面,其结构中的磁性四角架弯曲的同时原位释放精子[75]
Fig. 5 (a) Schematic diagram of the structure of magnetically driven nanomotors for targeted drug delivery[39];(b) The sperm-hybrid micromotor for targeted drug delivery. The drug-loaded sperm can be guided magnetically, and when the tetrapod of the micromotor hits a tumor spheroid, the tetrapod bends and releases the drug-loaded sperm[75]
图6 (a) 在4 MHz超声场中棒状马达的运动示意图,包括平面内旋转、轴向运动及链组装等[77];(b) 超声驱动的多孔纳米金马达用于药物靶向递送的示意图[38];(c) 超声驱动纳米马达用于递送siRNA的示意图,包括荧光图像[78]
Fig. 6 (a) Schematic illustration of the kinds of motion in a 4 MHz acoustic field, including in-plane rotation, axial directional motion, chain assembly, etc.[77];(b) Schematic of nanoporous Au nanomotors for targeted drug delivery under ultrasound field[38];(c) Schematic diagram of the acoustically propelled nanomotors for siRNA delivery, including fluorescence images[78]
图7 (a) Au-BP@SP Janus纳米马达在近红外照射下实现肿瘤光热治疗的示意图[87];(b) 巨噬细胞膜(MPCM)掩盖的Janus中孔二氧化硅纳米马达的制备及其用于肿瘤光热疗法的过程示意图[88];(c) 口腔细胞纳米马达对肿瘤细胞进行光热消融的示意图[89]
Fig. 7 (a) Schematic diagram of a Au-BP@SP Janus nanoparticle for PTT under NIR laser irradiation[87];(b) Schematic diagram of the fabrication of the MPCM-camouflaged Janus mesoporous silica nanomotor(MPCM@JMSNM) and its application in tumor photothermal therapy[88];(c) Schematic illustration for the autonomous photothermal ablation of cancer cells using the nanomotors[89]
图8 (a) RBCM微型马达的制备过程示意图;(b) RBCM微型马达应用于光动力疗法的原理示意图[94]
Fig. 8 (a) Schematic diagram of the fabrication of RBCM micromotors;(b) Schematic of ultrasound-powered and magnetically guided RBCM micromotors for the PDT[94]
[1]
Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšic M, Bonaventure A, Valkov M, Johnson C J, Estève J. et al. Lancet, 2018, 391:1023.

doi: S0140-6736(17)33326-3     pmid: 29395269
[2]
Chen H B, Gu Z J, An H W, Chen C Y, Chen J, Cui R, Chen S Q, Chen W H, Chen X S, Chen X Y, Chen Z, Ding B Q, Dong Q, Fan Q, Fu T, Hou D Y, Jiang Q, Ke H T, Jiang X Q, Liu G, Li S P, Li T, Liu Z, Nie G J, Ovais M, Pang D W, Qiu N S, Shen Y Q, Tian H Y, Wang C, Wang H, Wang Z Q, Xu H P, Xu J F, Yang X L, Zhu S, Zheng X C, Zhang X Z, Zhao Y B, Tan W H, Zhang X, Zhao Y L. Sci. China Chem., 2018, 61(12):1503.

doi: 10.1007/s11426-018-9397-5     URL    
[3]
Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. J. Control. Release, 2015, 200:138.

doi: 10.1016/j.jconrel.2014.12.030     URL    
[4]
Wang J J, Dong R F, Wu H Y, Cai Y P, Ren B Y. Nano-Micro Lett., 2020, 12:11.
[5]
Ren B Y, Cai Y P, Dong R F. Chin. Sci. Bull., 2017, 62(2/3):152.

doi: 10.1360/N972016-00843     URL    
[6]
Wei Y Y, Chen L, Wang J L, Yu S P, Liu X G, Yang Y Z. Prog. Chem., 2020, 32:381.
( 卫迎迎, 陈琳, 王军丽, 于世平, 刘旭光, 杨永珍. 化学进展, 2020, 32:381.).

doi: 10.7536/PC190739    
[7]
Wegner K D, Hildebrandt N. Chem. Soc. Rev., 2015, 44(14):4792.

doi: 10.1039/c4cs00532e     pmid: 25777768
[8]
Xia Y N, Li W Y, Cobley C M, Chen J Y, Xia X H, Zhang Q, Yang M X, Cho E C, Brown P K. Acc. Chem. Res., 2011, 44(10):914.

doi: 10.1021/ar200061q     URL    
[9]
Du X, Cui H, Zhao Q, Wang J, Chen H, Wang Y. Research, 2019, 2019:1.
[10]
Yu Q L, Li Z, Dou C Y, Zhao Y P, Gong J X, Zhang J F. Prog. Chem., 2020, 32:179.
( 于秋灵, 李政, 窦春妍, 赵义平, 巩继贤, 张健飞. 化学进展, 2020, 32:179.).

doi: 10.7536/PC190802    
[11]
Ye Z R, Sun Y Y, Zhang H, Song B, Dong B. Nanoscale, 2017, 9(46):18516.

doi: 10.1039/C7NR05896A     URL    
[12]
Zheng J, Dai B H, Wang J Z, Xiong Z, Yang Y, Liu J, Zhan X J, Wan Z H, Tang J Y. Nat. Commun., 2017, 8:1438.

doi: 10.1038/s41467-017-01778-9     pmid: 29127414
[13]
Wang W, Li S X, Mair L, Ahmed S, Huang T J, Mallouk T E. Angew. Chem., 2014, 126(12):3265.

doi: 10.1002/ange.201309629     URL    
[14]
Ahmed S, Wang W, Bai L J, Gentekos D T, Hoyos M, Mallouk T E. ACS Nano, 2016, 10(4):4763.

doi: 10.1021/acsnano.6b01344     URL    
[15]
Hu N, Wang L F, Zhai W H, Sun M M, Xie H, Wu Z G, He Q. Macromol. Chem. Phys., 2018, 219(5):1700540.

doi: 10.1002/macp.v219.5     URL    
[16]
Li J X, Angsantikul P, Liu W J, Esteban-Fernández de Ávila B, Chang X C, Sandraz E, Liang Y Y, Zhu S Y, Zhang Y, Chen C R, Gao W W, Zhang L F, Wang J. Adv. Mater., 2018, 30(2):1704800.

doi: 10.1002/adma.v30.2     URL    
[17]
Jiang J Z, Guo M H, Yao F Z, Li J, Sun J J. RSC Adv., 2017, 7(11):6297.

doi: 10.1039/C6RA25162E     URL    
[18]
Calvo-Marzal P, Sattayasamitsathit S, Balasubramanian S, Windmiller J R, Dao C, Wang J. Chem. Commun., 2010, 46(10):1623.

doi: 10.1039/b925568k     URL    
[19]
Su Y J, Ge Y, Liu L M, Zhang L N, Liu M, Sun Y Y, Zhang H, Dong B. ACS Appl. Mater. Interfaces, 2016, 8(6):4250.

doi: 10.1021/acsami.6b00012     URL    
[20]
Mou F Z, Chen C R, Ma H R, Yin Y X, Wu Q Z, Guan J G. Angew. Chem. Int. Ed., 2013, 52(28):7208.

doi: 10.1002/anie.201300913     URL    
[21]
Jiao J P, Xu D D, Liu Y H, Zhao W W, Zhang J H, Zheng T T, Feng H H, Ma X. Micromachines, 2018, 9(2):83.

doi: 10.3390/mi9020083     URL    
[22]
Ji Y X, Lin X K, Zhang H Y, Wu Y J, Li J B, He Q. Angew. Chem. Int. Ed., 2019, 58(13):4184.

doi: 10.1002/anie.v58.13     URL    
[23]
Wang J J, Dong R F, Yang Q X, Wu H Y, Bi Z J, Liang Q Y, Wang Q L, Wang C, Mei Y F, Cai Y P. Nanoscale, 2019, 11(35):16592.

doi: 10.1039/C9NR04295D     URL    
[24]
Zha F J, Wang T W, Luo M, Guan J G. Micromachines, 2018, 9(2):78.

doi: 10.3390/mi9020078     URL    
[25]
Xu B R, Mei Y F. Sci. Bull., 2017, 62(8):525.

doi: 10.1016/j.scib.2017.04.003     URL    
[26]
Tian Z A, Zhang L N, Fang Y F, Xu B R, Tang S W, Hu N, An Z H, Chen Z, Mei Y F. Adv. Mater., 2017, 29(13):1604572.

doi: 10.1002/adma.201604572     URL    
[27]
Paxton W F, Kistler K C, Olmeda C C, Sen A, St Angelo S K, Cao Y Y, Mallouk T E, Lammert P E, Crespi V H. J. Am. Chem. Soc., 2004, 126(41):13424.

doi: 10.1021/ja047697z     URL    
[28]
Li J, Xiao Q, Jiang J Z, Chen G N, Sun J J. RSC Adv., 2014, 4(52):27522.

doi: 10.1039/c4ra02959c     URL    
[29]
Wang J Z, Xiong Z, Zhan X J, Dai B H, Zheng J, Liu J, Tang J Y. Adv. Mater., 2017, 29(30):1701451.

doi: 10.1002/adma.201701451     URL    
[30]
Li J X, Liu W J, Wang J Y, Rozen I, He S, Chen C R, Kim H G, Lee H J, Lee H B R, Kwon S H, Li T L, Li L Q, Wang J, Mei Y F. Adv. Funct. Mater., 2017, 27(24):1700598.

doi: 10.1002/adfm.v27.24     URL    
[31]
Ahmed S, Wang W, Mair L O, Fraleigh R D, Li S X, Castro L A, Hoyos M, Huang T J, Mallouk T E. Langmuir, 2013, 29(52):16113.

doi: 10.1021/la403946j     URL    
[32]
Li T L, Zhang A N, Shao G B, Wei M S, Guo B, Zhang G Y, Li L Q, Wang W. Adv. Funct. Mater., 2018, 28(25):1870173.

doi: 10.1002/adfm.v28.25     URL    
[33]
Li L Q, Wang J Y, Li T L, Song W P, Zhang G Y. J. Appl. Phys., 2015, 117(10):104308.

doi: 10.1063/1.4915114     URL    
[34]
Jiang H R, Yoshinaga N, Sano M. Phys. Rev. Lett., 2010, 105(26):268302.

doi: 10.1103/PhysRevLett.105.268302     URL    
[35]
Wang J J, Wu H Y, Liu X Y, Liang Q Y, Bi Z J, Wang Z C, Cai Y P, Dong R F. Adv. Intell. Syst., 2020, 2(3):1900159.

doi: 10.1002/aisy.v2.3     URL    
[36]
Liu R, Sen A. J. Am. Chem. Soc., 2011, 133(50):20064.

doi: 10.1021/ja2082735     URL    
[37]
Kagan D, Benchimol M J, Claussen J C, Chuluun-Erdene E, Esener S, Wang J. Angew. Chem. Int. Ed., 2012, 51(30):7519.

doi: 10.1002/anie.201201902     URL    
[38]
Garcia-Gradilla V, Sattayasamitsathit S, Soto F, Kuralay F, Yardımcı C, Wiitala D, Galarnyk M, Wang J. Small, 2014, 10(20):4154.

doi: 10.1002/smll.201401013     pmid: 24995778
[39]
Gao W, Kagan D, Pak O S, Clawson C, Campuzano S, Chuluun-Erdene E, Shipton E, Fullerton E E, Zhang L F, Lauga E, Wang J. Small, 2012, 8(3):460.

doi: 10.1002/smll.201101909     URL    
[40]
Soper S A, Brown K, Ellington A, Frazier B, Garcia-Manero G, Gau V, Gutman S I, Hayes D F, Korte B, Landers J L, Larson D, Ligler F, Majumdar A, Mascini M, Nolte D, Rosenzweig Z, Wang J, Wilson D. Biosens. Bioelectron., 2006, 21(10):1932.

doi: 10.1016/j.bios.2006.01.006     URL    
[41]
Wen C Y, Wu L L, Zhang Z L, Liu Y L, Wei S Z, Hu J, Tang M, Sun E Z, Gong Y P, Yu J, Pang D W. ACS Nano, 2014, 8(1):941.

doi: 10.1021/nn405744f     URL    
[42]
Balasubramanian S, Kagan D, Jack Hu C M, Campuzano S, Lobo-Castañon M J, Lim N, Kang D Y, Zimmerman M, Zhang L F, Wang J. Angew. Chem. Int. Ed., 2011, 50(18):4161.

doi: 10.1002/anie.v50.18     URL    
[43]
Chang Z M, Wang Z, Shao D, Yue J, Xing H, Li L, Ge M F, Li M Q, Yan H Z, Hu H Z, Xu Q B, Dong W F. ACS Appl. Mater. Interfaces, 2018, 10(13):10656.

doi: 10.1021/acsami.7b19325     URL    
[44]
Lee H, Choi M, Lim J, Jo M, Han J Y, Kim T M, Cho Y. Theranostics, 2018, 8(2):505.

doi: 10.7150/thno.21967     URL    
[45]
Zhao L, Liu Y, Xie S Z, Ran P, Wei J J, Liu Q J, Li X H. Chem. Eng. J., 2020, 382:123041.

doi: 10.1016/j.cej.2019.123041     URL    
[46]
Stobiecka M, Chalupa A. J. Phys. Chem. B, 2015, 119(41):13227.

doi: 10.1021/acs.jpcb.5b07778     URL    
[47]
Gribko A, Künzel J, Wünsch D, Lu Q, Nagel S M, Knauer S K, Stauber R H, Ding G B. Int. J. Nanomed., 2019, 14:4187.

doi: 10.2147/IJN.S198319     pmid: 31289440
[48]
Castañeda A D, Brenes N J, Kondajji A, Crooks R M. J. Am. Chem. Soc., 2017, 139(22):7657.

doi: 10.1021/jacs.7b03648     URL    
[49]
Huang L, Li Z C, Huang S Q, Peter Reiss, Li L. Acta Chem. Sinica, 2017, 75:300.
( 黄璐, 李志春, 黄寿强, 李良. 化学学报, 2017, 75:300.).

doi: 10.6023/A16100543    
[50]
Zhao X L, Xu L G, Sun M Z, Ma W, Wu X L, Kuang H, Wang L B, Xu C L. Small, 2016, 12(34):4662.

doi: 10.1002/smll.v12.34     URL    
[51]
Li S, Xu L G, Ma W, Wu X L, Sun M Z, Kuang H, Wang L B, Kotov N A, Xu C L. J. Am. Chem. Soc., 2016, 138(1):306.

doi: 10.1021/jacs.5b10309     URL    
[52]
Zhang L, Liu X Y, Shen J J, Lu X M, Fan Q L, Huang W. Prog. Chem., 2013, 25:1375.

doi: 10.7536/PC121205    
( 张磊, 刘晓燕, 沈晶晶, 卢晓梅, 范曲立, 黄维. 化学进展, 2013, 25:1375.).

doi: 10.7536/PC121205    
[53]
Lu W J, Chen Y P, Liu Z, Tang W B, Feng Q, Sun J S, Jiang X Y. ACS Nano, 2016, 10(7):6685.

doi: 10.1021/acsnano.6b01903     URL    
[54]
Li J X, Esteban-Fernández de Ávila B, Gao W, Zhang L F, Wang J. Sci. Robot., 2017, 2(4):6431.
[55]
Qualliotine J R, Bolat G, Beltrán-Gastélum M, de Ávila B E F, Wang J, Califano J A. Otolaryngol. Neck Surg., 2019, 161(5):814.
[56]
Esteban-Fernández de Ávila B, Martín A, Soto F, Lopez-Ramirez M A, Campuzano S, Vásquez-Machado G M, Gao W W, Zhang L F, Wang J. ACS Nano, 2015, 9(7):6756.

doi: 10.1021/acsnano.5b02807     pmid: 26035455
[57]
Lee K, Lee A, Song B J, Kang C S. World J. Surg. Oncol., 2011, 9:139.

doi: 10.1186/1477-7819-9-139     URL    
[58]
Osborne C K, Bardou V, Hopp T A, Chamness G C, Hilsenbeck S G, Fuqua S A W, Wong J, Allred D C, Clark G M, Schiff R. JNCI J. Natl. Cancer Inst., 2003, 95(5):353.

doi: 10.1093/jnci/95.5.353     URL    
[59]
Beltrán-Gastélum M, Esteban-Fernández de Ávila B, Gong H, Venugopalan P L, Hianik T, Wang J, Subjakova V. ChemPhysChem, 2019, 20(23):3177.

doi: 10.1002/cphc.201900844     pmid: 31639248
[60]
De Lena M, Latorre A, Calabrese P, Catino A, Lorusso V, Mazzei A, Aloe A. J. Chemother., 2000, 12(4):367.

pmid: 10949988
[61]
Singal P K, Iliskovic N. N Engl J. Med., 1998, 339(13):900.

doi: 10.1056/NEJM199809243391307     URL    
[62]
Takemura G, Fujiwara H. Prog. Cardiovasc. Dis., 2007, 49(5):330.

pmid: 17329180
[63]
Krischke M, Hempel G, Völler S, André N, D’Incalci M, Bisogno G, Köpcke W, Borowski M, Herold R, Boddy A V, Boos J. Cancer Chemother. Pharmacol., 2016, 78(6):1175.

doi: 10.1007/s00280-016-3174-8     URL    
[64]
Barenholz Y C. J. Control. Release, 2012, 160(2):117.

doi: 10.1016/j.jconrel.2012.03.020     URL    
[65]
Brambilla D, Luciani P, Leroux J C. J. Control. Release, 2014, 190:9.

doi: 10.1016/j.jconrel.2014.03.056     pmid: 24794899
[66]
Szatrowski T P, Nathan C F. Cancer Res. 1991, 51:794.

pmid: 1846317
[67]
Choi H, Hwang B W, Park K M, Kim K S, Hahn S K. Part. Part. Syst. Charact., 2020, 37(1):1900418.

doi: 10.1002/ppsc.v37.1     URL    
[68]
Sattayasamitsathit S, Kou H H, Gao W, Thavarajah W, Kaufmann K, Zhang L F, Wang J. Small, 2014, 10(14):2830.

doi: 10.1002/smll.201303646     pmid: 24706367
[69]
Gao W, Dong R F, Thamphiwatana S, Li J X, Gao W W, Zhang L F, Wang J. ACS Nano, 2015, 9(1):117.

doi: 10.1021/nn507097k     URL    
[70]
de Ávila B E F, Angsantikul P, Li J X, Angel Lopez-Ramirez M, Ramírez-Herrera D E, Thamphiwatana S, Chen C R, Delezuk J, Samakapiruk R, Ramez V, Obonyo M, Zhang L F, Wang J. Nat. Commun., 2017, 8:272.

doi: 10.1038/s41467-017-00309-w     URL    
[71]
Li J X, Thamphiwatana S, Liu W J, Esteban-Fernández de Ávila B, Angsantikul P, Sandraz E, Wang J X, Xu T L, Soto F, Ramez V, Wang X L, Gao W W, Zhang L F, Wang J. ACS Nano, 2016, 10(10):9536.

doi: 10.1021/acsnano.6b04795     URL    
[72]
Wu Z G, Li L, Yang Y R, Hu P, Li Y, Yang S Y, Wang L V, Gao W. Sci. Robot., 2019, 4(32):eaax0613.

doi: 10.1126/scirobotics.aax0613     URL    
[73]
Llopis-Lorente A, García-Fernández A, Murillo-Cremaes N, Hortelão A C, Patiño T, Villalonga R, SancenÓn F, Martínez-Máñez R, Sánchez S. ACS Nano, 2019, 13(10):12171.

doi: 10.1021/acsnano.9b06706     pmid: 31580642
[74]
Tang S S, Zhang F Y, Gong H, Wei F N, Zhuang J, Karshalev E, Esteban-Fernández de Ávila B, Huang C Y, Zhou Z D, Li Z X, Yin L, Dong H F, Fang R H, Zhang X J, Zhang L F, Wang J. Sci. Robot., 2020, 5(43):eaba6137.

doi: 10.1126/scirobotics.aba6137     URL    
[75]
Xu H F, Medina-Sánchez M, Magdanz V, Schwarz L, Hebenstreit F, Schmidt O G. ACS Nano, 2018, 12(1):327.

doi: 10.1021/acsnano.7b06398     URL    
[76]
Jiao X Y, Wang Z M, Xiu J D, Dai W H, Zhao L, Xu T L, Du X, Wen Y Q, Zhang X J. Appl. Mater. Today, 2020, 18:100504.
[77]
Wang W, Castro L A, Hoyos M, Mallouk T E. ACS Nano, 2012, 6(7):6122.

doi: 10.1021/nn301312z     pmid: 22631222
[78]
Esteban-Fernández de Ávila B, Angell C, Soto F, Lopez-Ramirez M A, Báez D F, Xie S B, Wang J, Chen Y. ACS Nano, 2016, 10(5):4997.

doi: 10.1021/acsnano.6b01415     pmid: 27022755
[79]
Zhang Z J, Wang J, Chen C Y. Adv. Mater., 2013, 25(28):3869.

doi: 10.1002/adma.v25.28     URL    
[80]
Jaque D, Martínez Maestro L, del Rosal B, Haro-Gonzalez P, Benayas A, Plaza J L, Martín Rodríguez E, García Solé J. Nanoscale, 2014, 6(16):9494.

doi: 10.1039/c4nr00708e     pmid: 25030381
[81]
Li C X, Zhang Y F, Li Z M, Mei E C, Lin J, Li F, Chen C G, Qing X L, Hou L Y, Xiong L L, Hao H, Yang Y, Huang P. Adv. Mater., 2018, 30(8):1870049.

doi: 10.1002/adma.v30.8     URL    
[82]
Dolmans D E J G J, Fukumura D, Jain R K. Nat. Rev. Cancer, 2003, 3(5):380.

pmid: 12724736
[83]
Luo G F, Chen W H, Lei Q, Qiu W X, Liu Y X, Cheng Y J, Zhang X Z. Adv. Funct. Mater., 2016, 26(24):4339.

doi: 10.1002/adfm.v26.24     URL    
[84]
Chen W H, Luo G F, Qiu W X, Lei Q, Liu L H, Wang S B, Zhang X Z. Biomaterials, 2017, 117:54.

doi: 10.1016/j.biomaterials.2016.11.057     URL    
[85]
Maity S, Downen L N, Bochinski J R, Clarke L I. Polymer, 2011, 52(7):1674.

doi: 10.1016/j.polymer.2011.01.062     URL    
[86]
Schachoff R, Selmke M, Bregulla A P, Cichos F, Rings D, Chakraborty D, Kroy K, Günther K, Henning-Knechtel A, Sperling E, Mertig M. diffusion-fundamentals.org. 2015, 23:1.
[87]
Yang P P, Zhai Y G, Qi G B, Lin Y X, Luo Q, Yang Y, Xu A P, Yang C, Li Y S, Wang L, Wang H. Small, 2016, 12(39):5423.

doi: 10.1002/smll.v12.39     URL    
[88]
Xuan M J, Shao J X, Gao C Y, Wang W, Dai L R, He Q. Angew. Chem. Int. Ed., 2018, 57(38):12463.

doi: 10.1002/anie.201806759     URL    
[89]
Choi H, Lee G H, Kim K S, Hahn S K. ACS Appl. Mater. Interfaces, 2018, 10(3):2338.

doi: 10.1021/acsami.7b16595     URL    
[90]
Maas A L, Carter S L, Wileyto E P, Miller J, Yuan M, Yu G Q, Durham A C, Busch T M. Cancer Res., 2012, 72(8):2079.

doi: 10.1158/0008-5472.CAN-11-3744     URL    
[91]
Sahu A, Choi W I, Tae G. Adv. Therap., 2018, 1(4):1800026.

doi: 10.1002/adtp.v1.4     URL    
[92]
Liu K, Xing R R, Zou Q L, Ma G H, Möhwald H, Yan X H. Angew. Chem. Int. Ed., 2016, 55(9):3036.

doi: 10.1002/anie.201509810     URL    
[93]
Chatterjee D K, Fong L S, Zhang Y. Adv. Drug Deliv. Rev., 2008, 60(15):1627.

doi: 10.1016/j.addr.2008.08.003     URL    
[94]
Gao C Y, Lin Z H, Wang D L, Wu Z G, Xie H, He Q. ACS Appl. Mater. Interfaces, 2019, 11(26):23392.

doi: 10.1021/acsami.9b07979     URL    
[95]
You Y Q, Xu D D, Pan X, Ma X. Appl. Mater. Today, 2019, 16:508.
[96]
Yu M Z, Zhao K L, Zhu X H, Tang S Y, Nie Z, Huang Y, Zhao P, Yao S Z. Biosens. Bioelectron., 2017, 95:41.

doi: 10.1016/j.bios.2017.03.065     URL    
[97]
Izadifar Z, Babyn P, Chapman D. Ultrasound Med. Biol., 2017, 43(6):1085.

doi: S0301-5629(17)30052-2     pmid: 28342566
[98]
Sammet S. Abdom. Radiol., 2016, 41(3):444.

doi: 10.1007/s00261-016-0680-4     URL    
[99]
Hardell L, Sage C. Biomed. Pharmacother., 2008, 62(2):104.

doi: 10.1016/j.biopha.2007.12.004     URL    
[100]
Laakso I, Morimoto R, Heinonen J, Jokela K, Hirata A. Phys. Med. Biol., 2017, 62(17):6980.

doi: 10.1088/1361-6560/aa81fe     pmid: 28791963
[101]
Harden R N, Remble T A, Houle T T, Long J F, Markov M S, Gallizzi M A. Pain Pract., 2007, 7(3):248.

pmid: 17714104
[1] 何静, 陈佳, 邱洪灯. 中药碳点的合成及其在生物成像和医学治疗方面的应用[J]. 化学进展, 2023, 35(5): 655-682.
[2] 张婉萍, 刘宁宁, 张倩洁, 蒋汶, 王梓鑫, 张冬梅. 刺激响应性聚合物微针系统经皮药物递释[J]. 化学进展, 2023, 35(5): 735-756.
[3] 赵京龙, 沈文锋, 吕大伍, 尹嘉琦, 梁彤祥, 宋伟杰. 基于人体呼气检测应用的气体传感器[J]. 化学进展, 2023, 35(2): 302-317.
[4] 张荡, 王曦, 王磊. 生物酶驱动的微纳米马达在生物医学领域的应用[J]. 化学进展, 2022, 34(9): 2035-2050.
[5] 冯海弟, 赵璐, 白云峰, 冯锋. 纳米金属有机框架在肿瘤靶向治疗中的应用[J]. 化学进展, 2022, 34(8): 1863-1878.
[6] 陈晓峰, 王开元, 梁芳铭, 姜睿祺, 孙进. 外泌体递药系统及其在肿瘤治疗中的应用[J]. 化学进展, 2022, 34(4): 773-786.
[7] 钟琴, 周帅, 王翔美, 仲维, 丁晨迪, 傅佳骏. 介孔二氧化硅基智能递送体系的构建及其在各类疾病治疗中的应用[J]. 化学进展, 2022, 34(3): 696-716.
[8] 郭玲香, 李菊平, 刘志洋, 李全. 聚集诱导发光型光敏剂用于线粒体靶向光动力治疗[J]. 化学进展, 2022, 34(11): 2489-2502.
[9] 王嘉莉, 朱凌, 王琛, 雷圣宾, 杨延莲. 循环肿瘤细胞及细胞外囊泡的纳米检测技术[J]. 化学进展, 2022, 34(1): 178-197.
[10] 祝梓琳, 范中贤, 缪梦昭, 黄怀义. 铱(Ⅲ)配合物乏氧肿瘤光动力治疗[J]. 化学进展, 2021, 33(9): 1473-1481.
[11] 陈永杭, 李欣芳, 余伟江, 王幽香. 刺激响应聚合物微针在经皮给药中的应用[J]. 化学进展, 2021, 33(7): 1152-1158.
[12] 荆晓东, 孙莹, 于冰, 申有青, 胡浩, 丛海林. 肿瘤微环境响应药物递送系统的设计[J]. 化学进展, 2021, 33(6): 926-941.
[13] 许惠凤, 董永强, 朱希, 余丽双. 新型二维材料MXene在生物医学的应用[J]. 化学进展, 2021, 33(5): 752-766.
[14] 刘文杰, 刘凯会, 张彦伟, 王良, 张梦裔, 李静. 糖基化在新型冠状病毒侵染中的机制及药物研发中的应用[J]. 化学进展, 2021, 33(4): 524-532.
[15] 任飞, 石建兵, 佟斌, 蔡政旭, 董宇平. 具有聚集诱导发光性质的近红外荧光染料[J]. 化学进展, 2021, 33(3): 341-354.