聚多巴胺-阿霉素纳米颗粒对癌细胞的化疗-光热治疗协同作用

doi:10.7503/cjcu20141108

摘要/Abstract

摘要：

通过在水相中加入乙醇和氨水, 将单分子多巴胺聚合成具有良好光热转换能力的聚多巴胺纳米颗粒(PDA), 并利用π-π作用与共价键作用, 将抗癌药物阿霉素(Dox)负载到聚多巴胺纳米颗粒的表面, 制备了聚多巴胺纳米颗粒负载阿霉素(PDA-Dox), 研究了PDA-Dox的药物缓释性能. 结果发现, PDA-Dox能够在酸性环境下增加药物释放. 细胞实验显示, PDA-Dox配合激光照射, 能够通过化疗和光热治疗高效地杀死癌细胞.

关键词: 聚多巴胺纳米颗粒, 阿霉素, 化疗, 光热治疗

Abstract:

Polydopamine(PDA) nanoparticles were prepared with ethanol and ammonia in water, which performed an excellent light-heat energy conversion ability. An anti-cancer medicine, doxorubicin(Dox), was loaded on the surface of the polydopamine nanoparticles efficiently through π-π stacking and covalent bond, and then the doxorubicin loaded polydopamine(PDA-Dox) nanoparticles were prepared. The drug delivery property of the materials was studied. As a result, the drug release behavior could be controlled by the pH value of the environment, which was improved in acidic condition. When the PDA-Dox nanoparticles were exposed to the laser irradiation, the cancer cell, HeLa, could be killed efficiently by the materials through the chemo-photothermal synergistic therapy. Combined with the laser irradition, the nanomaterial could kill the cancer cell efficiently with the synergistic therapy between the phototherpy and chemotherapy in vitro.

Key words: Polydopamine nanoparticle, Doxorubicin, Chemotherpy, Photothermal therpy

中图分类号:

TrendMD:

刘宇炜, 郭卓. 聚多巴胺-阿霉素纳米颗粒对癌细胞的化疗-光热治疗协同作用. 高等学校化学学报, 2015, 36(7): 1389.

LIU Yuwei, GUO Zhuo. Polydopamine-doxorubicin Colloidal Nanoparticles for Chemo-Photothermal Synergistic Therapy Against Cancer Cell^†. Chem. J. Chinese Universities, 2015, 36(7): 1389.

图/表 10

Fig.1 TEM image(A) and histogram of particle size distribution(B) of PDA nanoparticles

Fig.2 UV-Vis absorption spectra of PDA nano-particles(a) and dopamine molecules(b) dispersed in aqueous solution

Fig.3 Temperature-time profiles of aqueous dispersions of PDA nanoparticles at different concentrations under NIR light irradiation(A) and temperature elevation of PDA nanoparticles dispersed in 1 mL of PBS solution(0.2 mg/mL) over five laser on/off cycles under NIR laser irradiation(B)(A) a. Water; cPDA/(mg·mL-1): b. 0.1; c. 0.2; d. 0.3; e. 0.5.

Fig.4 UV-Vis absorption spectra of solutions of Dox supernate before(a) and after(b) loading and PDA nanoparticles before(c) and after(d) loading

Fig.5 Fluorescence emission spectra of solutions of Dox supernate before(a) and after(b) loa-ding and PDA nanoparticles before(c) and after(d) loadingλex=470 nm.

Fig.6 FTIR spectra of PDA nanoparticles(a), Dox(b) and PDA-Dox nanoparticles(c)

Fig.7 Release profiles of Dox from PDA-Dox nano-particles at pH=5.5(a) and pH=7.4(b)

Fig.8 Viability of HeLa cells incubated with the PDA nanoparticles at different concentrationsa. Control; cPDA/(μg·mL-1) from b to h: 20, 40, 80, 160, 320, 640, 1280.

Fig.9 Viability of HeLa cells incubated with PBS control(a), free Dox(b), PDA nanoparticles(c) and PDA-Dox nanoparticles(d) with and without NIR irradiation at 2 W/cm2

Fig.10 Confocal images of HeLa cells incubated with DMEM medium(A), PDA nanoparticles(B, C) and PDA-Dox nanoparticles(D) dispersed in DMEM for 24 h at 37 ℃ without(A, B) and with(C, D) NIR irradiation at 2 W/cm2 for 5 min

参考文献 22

[1]	Song X. L., You J., Wang J., Zhu A. P., Li L. J., Guo R., Chem. Res. Chinese Universities, 2014, 30(2), 326—332
[2]	Si J. Y., Yang H., Mater. Chem. Phys., 2011, 128(3), 519—524
[3]	Wei Y. F., Kong J. H., Yang L. P., Ke L., Tan H. R., Liu H., Huang Y. Z., Sun X. W., Lu X. H., Du H. J., J. Mater. Chem. A, 2013, 1(16), 5045—5052
[4]	Liu Y., Jin H. B., Zhu S. M., Liu Y. C., Long M. C., Zhou Y. F., Yan D. Y., Nanotechnology, 2012, 23(32), 325602—325611
[5]	Jiang H., Yang L. P., Li C. Z., Yan C. Y., Lee P. S., Ma J., Energy & Environmental Science, 2011, 4(5), 1813—1819
[6]	Liu Q. Z., Yu B., Ye W. C., Zhou F., Macromolecular Bioscience, 2011, 11(9), 1227—1234
[7]	Cui J. W., Yan Y., Such G. K., Liang K., Ochs C. J., Postma A., Caruso F., Biomacromolecules, 2012, 13(8), 2225—2228
[8]	Ma Z. Y., Jia X., Hu J. M., Zhang G. X., Zhou F., Liu Z. Y., Wang H. Y., Langmuir, 2013, 29(19), 5631—5637
[9]	Park J. Y., Brust T. F., Lee H. J., Lee S. C., Watts V. J., Yeo Y., ACS Nano, 2014, 8(4), 3347—3356
[10]	Huang X. H., Ei-Sayed I. H., Qian W., El-Sayed M. A., J. Am. Chem. Soc., 2006, 128(6), 2115—2120
[11]	Liu Y. L., Ai K. L., Liu J. H., Deng M., He Y. Y., Lu L. H., Adv. Mater., 2013, 25(9), 1353—1359
[12]	Zhu M. T., Nie G. J., Meng H., Xia T., Nel A., Zhao Y. L., Accounts of Chemical Research, 2013, 46(3), 622—631
[13]	Xu H. L., Liu X. K., Wang D. Y., Chem. Mater., 2011, 23(23), 5105—5110
[14]	Ding X. G., Liow C. H., Zhang M. X., Huang R. J., Li C. Y., Shen H., Liu M. Y., Zou Y., Gao N., Zhang Z. J., Li Y. G., Wang Q. B., Li S. Z., Jiang J., J. Am. Chem. Soc., 2014, 136(44), 15684—15693
[15]	Lin L. S., Cong Z. X., Cao J. B., Ke K. M., Peng Q. L., Gao J. H., Yang H. H., Liu G., Chen X. Y., ACS Nano, 2014, 8(4), 3876—3883
[16]	Tian Q. W., Hu J. Q., Zhu Y. H., Zou R. J., Chen Z. G., Yang S. P., Li R. W., Su Q. Q., Han Y., Liu X. G., J. Am. Chem. Soc., 2013, 135(23), 8571—8577
[17]	Yu X., Fan H. L., Liu Y., Shi Z. J., Jin Z. X., Langmuir, 2014, 30(19), 5497—5505
[18]	Das G., Nicastri A., Coluccio M. L., Gentile F., Candeloro P., Cojoc G., Liberale C., Angelis F. D., Fabrizio E. D., Microscopy Research and Technique, 2010, 73(10), 991—995
[19]	Mok H., Veiseh O., Fang C., Kievit F. M., Wang F. Y., Park J. O., Zhang M. Q., Molecular Pharmaceutics, 2010, 7(6), 1930—1939
[20]	Padilla P. S., Matos P. M., Kondo N., Marin M., Santos N. C., Melikyan G. B., Proceedings of the National Academy of Sciences, 2012, 109(43), 17627—17632
[21]	Zheng Q. S., Lin T. R., Wu H. Y., Guo L. Q., Ye P. R., Hao Y. L., Guo Q. Q., Jiang J. Z., Fu F. F., Chen G. N., International Journal of Pharmaceutics, 2014, 463(1), 22—26
[22]	Sun X. M., Liu Z., Welsher K., Robinson J. T., Goodwin A., Zaric S., Dai H. J., Nano Research, 2008, 1(3), 203—212