Platinum(Ⅳ) Prodrug-grafted Phosphorothioate DNA and Its Self-assembled Nanostructure for Targeted Drug Delivery

doi:10.7503/cjcu20200283

Abstract

Abstract: cis-Platin drugs play a vital role in the clinical treatment of various cancers. However, its poor water solubility, non-targeting capability and severe side effects result in limited antitumor efficacy and greatly impede its clinic practices. To address these challenges, we successfully graft a multitude of Pt(Ⅳ) prodrugs on a diblock DNA that consists of a regular phosphodiester DNA segment with MUC-1 aptamer sequence and a phosphorothioate(PS) ploy T segment. After being modified with iodoacetate moiety, the prodrug can efficiently react with PS groups and grafted onto the backbone of PS segment, resulting in the formation of an MUC-1/^PODNA-b-(^PSDNA-g-Pt) conjugate. Owing to its amphiphilic feature, the obtained DNA-drug conjugate(DDC) could further self-assembled into spherical nucleic acid like nanostructure(MUC-1/Pt-SNAs) to serve as a new drug delivery system. With the presence of MUC-1 aptamer on particle surface, MUC-1/Pt-SNAs can actively target the tumor cells overexpressed MUC-1 proteins and internalize into cells with high efficiency. Together with a high drug loading ratio(39.6%) achieved by simple and convenient conjugation method, the obtained DNA-based targeted delivery system shows substantial antitumor effect and low side effects both in vitro and in vivo.

Key words: Platinum prodrug, Phosphorothioate DNA, Targeted drug delivery, Spherical nucleic acid, MUC-1 aptamer

CLC Number:

O626.413

TrendMD:

REN Yushuang, GUO Yuanyuan, LIU Xueyi, SONG Jie, ZHANG Chuan. Platinum(Ⅳ) Prodrug-grafted Phosphorothioate DNA and Its Self-assembled Nanostructure for Targeted Drug Delivery[J]. Chem. J. Chinese Universities, 2020, 41(8): 1721.

References 44

[1]	Siegel R. L., Miller K. D., Jemal A., CA-Cancer J. Clin., 2019, 69(1), 7-34
[2]	Ferlay J., Colombet M., Soerjomataram I., Mathers C., Parkin D. M., Pineros M., Znaor A., Bray F., Int. J. Cancer, 2019, 144(8), 1941-1953
[3]	Li L., Xu X. R., Li Y. Q., Zhang C. F., Chem. J. Chinese Univversity, 2019, 40(9), 1998-2004(李林, 许鑫汝, 李英奇, 张彩凤. 高等学校化学学报, 2019, 40(9), 1998-2004)
[4]	Moncharmont C., Auberdiac P., Mélis A., Afqir S., Magné N., Bull. Cancer, 2011, 98(2), 164-175
[5]	Johnstone T. C., Suntharalingam K., Lippard S. J., Chem Rev., 2016, 116(5), 3436-3486
[6]	McKeage M. J., Expert Opin. Invest. Drugs, 2001, 10(1), 119-128
[7]	Brabec V., Prog. Nucleic Acid Res. Mol. Biol., 2002, 71, 1-68
[8]	Dan G., J. Inorg. Biochem., 2019, 191, 77-84
[9]	Xu S. T., Zhu X. Y., Zhang C., Huang W., Zhou Y. F., Yan D. Y., Nat. Commun., 2018, 9(1), 2053
[10]	Gao M. M., Wang C. L., Dou H. J., Xu G. X., Chem. J. Chinese Univversity, 2019, 40(6), 1301-1309(高苗苗, 王成龙, 窦红静, 许国雄. 高等学校化学学报, 2019, 40(6), 1301-1309)
[11]	Xu S. T., Zhu X. Y., Huang W., Zhou Y. F., Yan D. Y., J. Controlled Release, 2017, 266, 36-46
[12]	Hall M. D., Okabe M., Shen D. W., Liang X. J., Gottesman M. M., Annu. Rev. Pharmacol. Toxicol., 2008, 48, 495-535
[13]	Okabe M., Szakacs G., Suzuki T., Gottesman M. M., Gastroenterology, 2007, 132(4), A631-A631
[14]	Huttunen K. M., Raunio H., Rautio J., Pharmacol. Rev., 2011, 63(3), 750-771
[15]	Guo D. B., Xu S. T., Huang Y., Jiang H. Y., Yasen W., Wang N., Su Y., Qian J. W., Li J., Zhang C., Zhu X. Y., Biomaterials, 2018, 177, 67-77
[16]	Qian Q. H., Shi L. L., Gao X. H., Ma Y., Yang J. P., Zhang Z. H., Qian J. W., Zhu X. Y., Small, 2019, 15(47), e1903208
[17]	Lee D. S., Qian H., Tay C. Y., Leong D. T., Chem. Soc. Rev., 2016, 45(15), 4199-4225
[18]	Ling X., Chen X., Riddell I. A., Tao W., Wang J., Hollett G., Lippard S. J., Farokhzad O. C., Shi J., Wu J., Nano Lett., 2018, 18(7), 4618-4625
[19]	Bi H.T., Dai Y. L., Yang P. P., Xu J. T., Yang D., Gai S. L., He F., Liu B., Zhong C. N., An G. H., Lin J., Small, 2018, 14(13), e1703809
[20]	Petruzzella E., Sirota R., Solazzo I., Gandin V., Gibson D., Chem. Sci., 2018, 9(18), 4299-4307
[21]	Qian Q. H., Zhu L. J., Zhu X. Y., Sun M., Yan D. Y., Matter, 2019, 1(6), 1618-1630
[22]	Azhdarzadeh M., Atyabi F., Saei A. A., Varnamkhasti B. S., Omidi Y., Fateh M., Ghavami M., Shanehsazzadeh S., Dinarvand R., Colloids Surf. B, 2016, 143, 224-232
[23]	Cai L., Chen Z. Z., Chen M. Y., Tang H. W., Pang D. W., Biomaterials, 2013, 34(2), 371-381
[24]	Alibolandi M., Hoseini F., Mohammad M., Ramezani P., Einafshar E., Taghdisi S. M., Ramezani M., Abnous K., Int. J. Pharm., 2018, 549(1), 67-75
[25]	Felgner P. L., Ringold G. M., Nature, 1989, 337(6205), 387-388
[26]	Farhood H., Serbina N., Huang L., Biochim. Biophys. Acta, 1995, 1235(2), 289-295
[27]	Al-Jamal W. T., Kostarelos K., Acc. Chem. Res., 2011, 44(10), 1094-1104
[28]	Pack D. W., Hoffman A. S., Pun S., Stayton P. S., Nat. Rev. Drug Discovery, 2005, 4(7), 581-593
[29]	Duncan B., Kim C., Rotello V. M., J. Controlled Release, 2010, 148(1), 122-127
[30]	Chan M., Esteve D., Fourniols J. Y., Escriba C., Campo E., Artif. Intell. Med., 2012, 56(3), 137-156
[31]	Basu U., Banik B., Wen R., Pathak R. K., Dhar S., Dalton Trans., 2016, 45(33), 12992-13004
[32]	Williams S. C. P., Proc. Natl. Acad. Sci. USA, 2013, 110(33), 13231-13233
[33]	Zhang L. H., Cao S. T., Liu J. B., Zuo X. L., Wang L. H., Fan C. H., Li J., Chem. J. Chinese Univversity, 2020, 41(6), 1151-1162(张露灏, 曹书婷, 刘江波, 左小磊, 王丽华, 樊春海, 李江. 高等学校化学学报, 2020, 41(6), 1151-1162)
[34]	Liu T., Song P., Marcher A., Kjems J., Yang C., Gothelf K. V., Chembiochem., 2019, 20(8), 1014-1018
[35]	Fakhoury J. J., McLaughlin C. K., Edwardson T. W., Conway J. W., Sleiman H. F., Biomacromolecules, 2014, 15(1), 276-282
[36]	Wang D.L., Liu B., Ma Y., Wu C. W., Mou Q. B., Deng H. P., Wang R. B., Yan D. Y., Zhang C., Zhu X. Y., J. Am. Chem. Soc., 2017, 139(40), 14021-14024
[37]	Zhang C., Li X., Tian C., Yu G. M., Li Y. L., Jiang W., Mao C. D., ACS Nano, 2014, 8(2), 1130-1135
[38]	Wei M., Chen N., Li J., Yin M., Liang L., He Y., Song H. Y., Fan C. H., Huang Q., Angew. Chem. Int. Ed., 2012, 51(5), 1202-1206
[39]	Tan X., Lu X., Jia F., Liu X., Sun Y., Logan J. K., Zhang K., J. Am. Chem. Soc., 2016, 138(34), 10834-10837
[40]	Li F. F., Lu J., Liu J., Liang C., Wang M. L., Wang L. Y., Li D. F., Yao H. Z., Zhang Q. L., Wen J., Zhang Z. K., Li J., Lv Q. X., He X. J., Guo B. S., Guan D. G., Yu Y. Y., Dang L., Wu X. H., Li Y. S., Chen G. F., Jiang F., Sun S. G., Zhang B. T., Lu A., Zhang G., Nat. Commun., 2017, 8(1), 1390-1404
[41]	Guo Y. Y., Zhang J., Ding F., Pan G. F., Li J., Feng J., Zhu X. Y., Zhang C., Adv. Mater., 2019, 31(16), e1807533
[42]	Zhang J., Guo Y. Y., Ding F., Pan G. F., Zhu X. Y., Zhang C., Angew. Chem. Int. Ed., 2019, 58(39), 13794-13798
[43]	Chin C. F., Tian Q., Setyawati M. I., Fang W., Tan E. S. Q., Leong D. T., Ang W. H., J. Med.Chem., 2012, 55(17), 7571-7582
[44]	Yap S. Q., Chin C. F., Thng A. H. H., Pang Y. Y., Ho H. K., Ang W. H., Chemmedchem., 2017, 12(4), 300-311