纳米药物载体聚酰胺胺的细胞毒性研究

引用本文: 李俊锋, 张清荣, 付彦丰, 李思莹, 刘禹麟, 周晶, 蔡明军, 杨国程, 单玉萍. 纳米药物载体聚酰胺胺的细胞毒性研究[J]. 分析化学, 2021, 49(6): 999-1007. doi: 10.19756/j.issn.0253-3820.211129 shu

Citation: LI Jun-Feng, ZHANG Qing-Rong, FU Yan-Feng, LI Si-Ying, LIU Yu-Lin, ZHOU Jing, CAI Ming-Jun, YANG Guo-Cheng, SHAN Yu-Ping. Study on Cytotoxicity of Nanodrug Carrier-Polyamidoamine Dendrimers[J]. Chinese Journal of Analytical Chemistry, 2021, 49(6): 999-1007. doi: 10.19756/j.issn.0253-3820.211129 shu

纳米药物载体聚酰胺胺的细胞毒性研究

李俊锋 ^1, ,
张清荣 ^1, ,
付彦丰 ^1, ,
李思莹 ^1, ,
刘禹麟 ^1, ,
周晶 ^1, ,
蔡明军 ^2, ,
杨国程 ^1, ,
单玉萍 ^{1,
,}

1.
长春工业大学化学与生命科学学院, 材料科学高等研究院, 长春 130012;
2.
中国科学院长春应用化学研究所, 电分析化学国家重点实验室, 长春 130022

通讯作者: 单玉萍,E-mail:shanyp@mail.ccut.edu.cn

基金项目:
国家自然科学基金项目（No.21773017）资助。

摘要: 聚酰胺胺（PAMAM）是具有双亲性的树枝状大分子，载药能力良好，已成为纳米药物转运体系中重要的药物载体。在近生理环境下，实时测量不同代数（G2、G5和G7）、不同末端基团（—OH、—NH₂和—COOH） PAMAM的细胞毒性，对于其作为药物载体的应用尤为重要。本研究利用原子力显微镜（AFM）纳米压痕技术可以在生理条件下测量单个细胞力学性质的优势，通过比较浓度梯度和时间梯度下不同代数及不同末端基团PAMAM对细胞力学性质（杨氏模量）的影响，分析了PAMAM的细胞毒性。由于没有明显的电荷效应，不同浓度的G2-PAMAM-NH₂和G5-PAMAM-OH与HeLa细胞共孵育不同时间后，细胞杨氏模量的改变（毒性）并不明显。以0.5 μmol/L G5-PAMAM-NH₂与HeLa细胞共孵育0、0.5、1和2 h后，细胞杨氏模量分别为0.61、0.45、0.46和0.22 kPa；分别以0.5、1.0、2.0和5.0 μmol/L G5-PAMAM-NH₂与HeLa细胞共孵育2 h后，细胞杨氏模量分别为0.30、0.20、0.17和0.22 kPa。由此可知，时间是影响其细胞毒性的主导因素。不同末端基团的G5-PAMAM-COOH的细胞毒性具有浓度依赖性。本研究为PAMAM作为纳米药物载体在纳米医学中的应用提供了基础数据。

关键词:

English

Study on Cytotoxicity of Nanodrug Carrier-Polyamidoamine Dendrimers

1.
School of Chemistry and Life Science, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, China;
2.
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China

Corresponding author: SHAN Yu-Ping, shanyp@mail.ccut.edu.cn

Received Date: 19 February 2021
Revised Date: 14 April 2021
Fund Project:
Supported by the National Natural Science Foundation of China(No.201773017).

Abstract: Due to the excellent drug loading capacity, the amphiphobic dendritic macromolecule polyamide amine (PAMAM) has become an important drug carrier in nanodrug transport system. Therefore, real-time measurement of the cytotoxicity of different generations and different terminal groups of PAMAM in the near physiological environment is particularly important for drug carrier screening. In this study, taking the advantages of atomic force microscopy (AFM)-based nanoindentation technology for measuring the mechanical properties of individual cells under physiological conditions, the cell mechanical properties (Young's modulus) were compared after coincubation with different generations and different terminal groups of PAMAM at different concentrations for different tme, and the cytotoxicity of PAMAM was analyzed. Because there was no obvious charge effect, the change of Young's modulus of HeLa cells coincubated with G2-PAMAM-NH₂ and G5-PAMAM-OH at different concentrations for different time was not obvious. The Young's modulus of HeLa cells was 0.61, 0.45, 0.46 and 0.22 kPa after coincubation with 0.5 μmol/L G5-PAMAM-NH₂ for 0 h, 0.5 h, 1 h and 2 h, respectively. The Young's modulus of HeLa cells were 0.30, 0.20, 0.17 and 0.22 kPa after coincubation with G5-PAMAM-NH₂ for 2 h at 0.5, 1.0, 2.0 and 5.0 μmol/L, respectively. It was found that the coincubation time was the dominant factor of cytotoxicity, while the cytotoxicity of G5-PAMAM-COOH was concentration-dependent. This study would lay a theoretical foundation for the better application of PAMAM in nanomedicine as a nanodrug carrier.

Key words:

1. [1]
  JAIN N K, PRAJAPATI R, AGARWAL A, GUPTA U, ASTHANA A. Asian J. Pharm., 2009, 3(3): 188-196.
2. [2]
  TORRES-PEREZ S A, RAMOS-GODINEZ M D P, RAMON-GALLEGOS E. J. Drug Delivery Sci. Technol., 2020, 58(1): 101769.
3. [3]
  YOYEN-ERMIS D, OZTURK-ATAR K, KURSUNEL M A, AYDIN C, OZKAZANC D, GURBUZ M U, UNER A, TULU M, CALIS S, ESENDAGLI G. Mol. Pharmaceutics, 2018, 15(4): 1526-1533.
4. [4]
  LIU D F, WANG C, YANG J, AN Y L, YANG R, TENG G J. ACS Omega, 2020, 5(16): 9316-9323.
5. [5]
  MUNDER A, MOSKOVITZ Y, MEIR A, KAHREMANY S, LEVY L, KOLITZ-DOMB M, COHEN G, SHTRIKER E, VISKIND O, LELLOUCHE J P, SENDEROWITZ H, CHESSLER S D, KORSHIN E E, RUTHSTEIN S, GRUZMAN A. Medchemcomm, 2019, 10(2): 280-293.
6. [6]
  SHEN W, DONGEN M A, HAN Y C, YU M M, LI Y Z, LIU G, BANASZAK H M M, QI R. Eur. J. Pharm. Biopharm., 2014, 88(3): 658-663.
7. [7]
  CAMINADE A M, FRUCHON S, TURRIN C O, POUPOT M, OUALI A, MARAVAL A, GARZONI M, MALY M, FURER V, KOVALENKO V, MAJORAL J P, PAVAN G M, POUPOT R. Nat. Commun., 2015, 6: 7722.
8. [8]
  EL-SAYED M, GINSKI M, RHODES C, GHANDEHARI H. J. Controlled Release, 2002, 81(3): 355-365.
9. [9]
  TERAMURA Y, KANEDA Y, TOTANI T, IWATA H. Biomaterials, 2008, 29(10): 1345-1355.
10. [10]
  ZENG Y, KUROKAWA Y, WIN-SHWE T T, ZENG Q, HIRANO S, ZHANG Z Y, SONE H. J. Toxicol. Sci., 2016, 41(3): 351-369.
11. [11]
  LEROUEIL P R, BERRY S A, DUTHIE K, HAN G, ROTELLO V M, MCNERNY D Q, BAKER J J R, ORR B G, BANASZAK H M M. Nano Lett., 2008, 8(2): 420-424.
12. [12]
  HONG S, LEROUEIL P R, JANUS E K, PETERS J L, KOBER M M, ISLAM M T, ORR B G, BAKER J J R,BANASZAK H M M. Bioconjugate Chem., 2006, 17(3): 728-734.
13. [13]
  CHEN J M, HESSLER J A, PUTCHAKAYALA K, PANAMA B K, KHAN D P, HONG S, MULLEN D G, DIMAGGIO S C, SOM A, TEW G N, LOPATIN A N, BAKER J J R, BANASZAK H M M, ORR B G. J. Phys. Chem. B, 2009, 113(32): 11179-11185.
14. [14]
  LEROUEIL P R, HONG S, MECKE A, BAKER J R J R, ORR B G, BANASZAK H M M. Acc. Chem. Res., 2007, 40(5): 335-342.
15. [15]
  DUNCAN R, IZZO L. Adv. Drug Delivery Rev., 2005, 57(15): 2215-2237.
16. [16]
  LEE J H, CHA K E, KIM M S, HONG H W, CHUNG D J, RYU G, MYUNG H. Toxicol. Lett., 2009, 190(2): 202-207.
17. [17]
  EVANS K O, LASZLO J A, COMPTON D L. Biochim. Biophys. Acta, Biomembr., 2014, 1838(1): 445-455.
18. [18]
  TAMAYO-BELDA M, GONZALEZ-PLEITER M, PULIDO-REYES G, MARTIN-BETANCOR K, LEGANES F, ROSAL R, FERNANDEZ-PINAS F. Environ. Sci.: Nano, 2019, 6(3): 863-878.
19. [19]
  WANG L, TIAN L G, ZHANG W X, WANG Z B, LIU X P. Micromachines, 2020, 11(6): 562.
20. [20]
  ALCARAZ J, OTERO J, JORBA I, NAVAJAS D. Semin. Cell Dev. Biol., 2018, 73(1): 71-81.
21. [21]
  ODDONE N, ZAMBRANA A I, TASSANO M, PORCAL W, CABRAL P, BENECH J C. J. Nanopart. Res., 2013, 15(7): 1776.
22. [22]
  REBELO L M, SOUSA J S, FILHO J M, RADMACHER M. Nanotechnology, 2013, 24(5): 055102.
23. [23]
  HELVERT S, FRIEDL P. ACS Appl. Mater. Interfaces, 2016, 8(34): 21946-21955.
24. [24]
  ZHAO P P, CHEN L S, SHAO H, ZHANG Y N, SUN Y Q, KE Y, RAMAKRISHNA S, HE L M, XUE W. Biomed. Mater. (Bristol, U. K.), 2016, 11(1): 015021.
25. [25]
  VIDAL F, VASQUEZ P, DIAZ C, NOVA D, ALDERETE J, GUZMAN L. Mol. Pharmaceutics, 2016, 13(10): 3395-3403.
26. [26]
  ALBERTAZZI L, SERRESI M, ALBANESE A, BELTRAM F. Mol. Pharmaceutics, 2010, 7(3): 680-688.
27. [27]
  HUANG M, MA Z S, KHOR E, LIM L Y. Pharm. Res., 2002, 19(10): 1488-1494.
28. [28]
  LI H J, LIU J, LUO Y L, CHEN S B, LIU R, DU J Z, WANG J. Nano Lett., 2019, 19(12): 8947-8955.
29. [29]
  PARIMI S, BARNES J T, CALLEN D F, PRESTIDGE C A. Biomacromolecules, 2010, 11(2): 382-389.
30. [30]
  MORRIS C J, ALJAYYOUSSI G, MANSOUR O, GRIFFITHS P, GUMBLETON M. Pharm. Res., 2017, 34(12): 2517-2531.
31. [31]
  KOLHE P, MISRA E, KANNAN R M, KANNAN S, LIEH-LAI M. Int. J. Pharm. (Amsterdam, Neth.), 2003, 259(1-2): 143-160.

扫一扫看文章

计量

PDF下载量: 14
文章访问数: 1155
HTML全文浏览量: 227

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

纳米药物载体聚酰胺胺的细胞毒性研究

通讯作者: 单玉萍,E-mail:shanyp@mail.ccut.edu.cn

English

Study on Cytotoxicity of Nanodrug Carrier-Polyamidoamine Dendrimers

Corresponding author: SHAN Yu-Ping, shanyp@mail.ccut.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

纳米药物载体聚酰胺胺的细胞毒性研究

通讯作者: 单玉萍,E-mail:shanyp@mail.ccut.edu.cn

English

Study on Cytotoxicity of Nanodrug Carrier-Polyamidoamine Dendrimers

Corresponding author: SHAN Yu-Ping, shanyp@mail.ccut.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

文章相关

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs