Abstract
The selective identification and removal of senescent cells including senescent cancer cells are very important to prolong life and improve the treatment efficacy of cancer therapy. In this study, we integrated the high selectivity of enzyme-instructed self-assembly (EISA) and efficient reactive oxygen species (ROS) generating property of a novel luminogen with aggregation-induced emission (AIE) character to selectively identify and remove senescent HeLa (s-HeLa) cells. The s-HeLa cells expressed high levels of β-galactosidase (β-Gal), which led to the selective accumulation and formation of nanomaterials of Comp. 1 in the cells. Upon white light irradiation, the nanomaterials efficiently produced ROS and therefore killed s-HeLa cells. Our study demonstrated a promising strategy to selectively remove senescent cells and improve the treatment efficacy of cancer therapy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
He S, Sharpless NE. Cell, 2017, 169: 1000–1011
Saleh T, Tyutyunyk-Massey L, Gewirtz DA. Cancer Res, 2019, 79: 1044–1046
Zhang B, Fu D, Xu Q, Cong X, Wu C, Zhong X, Ma Y, Lv Z, Chen F, Han L, Qian M, Chin YE, Lam EWF, Chiao P, Sun Y. Nat Commun, 2018, 9: 1723
Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, Dörr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dörken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt CA. Nature, 2018, 553: 96–100
Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, Janakiraman K, Sharpless NE, Ding S, Feng W, Luo Y, Wang X, Aykin-Burns N, Krager K, Ponnappan U, Hauer-Jensen M, Meng A, Zhou D. Nat Med, 2016, 22: 78–83
Scudellari M. Nature, 2017, 550: 448–450
Celli JP, Spring BQ, Rizvi I, Evans CL, Samkoe KS, Verma S, Pogue BW, Hasan T. Chem Rev, 2010, 110: 2795–2838
Dolmans DEJGJ, Fukumura D, Jain RK. Nat Rev Cancer, 2003, 3: 380–387
Wang D, Su H, Kwok RTK, Hu X, Zou H, Luo Q, Lee MMS, Xu W, Lam JWY, Tang BZ. Chem Sci, 2018, 9: 3685–3693
Xu S, Yuan Y, Cai X, Zhang CJ, Hu F, Liang J, Zhang G, Zhang D, Liu B. Chem Sci, 2015, 6: 5824–5830
Liang J, Tang BZ, Liu B. Chem Soc Rev, 2015, 44: 2798–2811
Ding S, Liu M, Hong Y. Sci China Chem, 2018, 61: 882–891
Zhou Y, Liu H, Zhao N, Wang Z, Michael MZ, Xie N, Tang BZ, Tang Y. Sci China Chem, 2018, 61: 892–897
Bai Y, Liu D, Han Z, Chen Y, Chen Z, Jiao Y, He W, Guo Z. Sci China Chem, 2018, 61: 1413–1422
Baysec S, Minotto A, Klein P, Poddi S, Zampetti A, Allard S, Cacialli F, Scherf U. Sci China Chem, 2018, 61: 932–939
Shimizu M, Nakatani M, Nishimura K. Sci China Chem, 2018, 61: 925–931
Wang Z, Zhou F, Wang J, Zhao Z, Qin A, Yu Z, Tang BZ. Sci China Chem, 2018, 61: 76–87
Jurk D, Wang C, Miwa S, Maddick M, Korolchuk V, Tsolou A, Gonos ES, Thrasivoulou C, Jill Saffrey M, Cameron K, von Zglinicki T. Aging Cell, 2012, 11: 996–1004
Shi J, Schneider JP. Angew Chem, 2019, 13844–13848
Tang W, Zhao Z, Chong Y, Wu C, Liu Q, Yang J, Zhou R, Lian ZX, Liang G. ACS Nano, 2018, 12: 9966–9973
Wang H, Liu J, Han A, Xiao N, Xue Z, Wang G, Long J, Kong D, Liu B, Yang Z, Ding D. ACS Nano, 2014, 8: 1475–1484
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O. Proc Natl Acad Sci USA, 1995, 92: 9363–9367
Brown N, Lei J, Zhan C, Shimon LJW, Adler-Abramovich L, Wei G, Gazit E. ACS Nano, 2018, 12: 3253–3262
Kubota R, Liu S, Shigemitsu H, Nakamura K, Tanaka W, Ikeda M, Hamachi I. Bioconjugate Chem, 2018, 29: 2058–2067
Zhao F, Weitzel CS, Gao Y, Browdy HM, Shi J, Lin HC, Lovett ST, Xu B. Nanoscale, 2011, 3: 2859–2861
Wang H, Feng Z, Qin Y, Wang J, Xu B. Angew Chem Int Ed, 2018, 57: 4931–4935
Yang Z, Liang G, Wang L, Xu B. J Am Chem Soc, 2006, 128: 3038–3043
Zhan J, Cai Y, He S, Wang L, Yang Z. Angew Chem Int Ed, 2018, 57: 1813–1816
Xu T, Cai Y, Zhong X, Zhang L, Zheng D, Gao Z, Pan X, Wang F, Chen M, Yang Z. Chem Commun, 2019, 7175–7178
Chang B-D, Broude EV, Dokmanovic M, Zhu H, Ruth A, Xuan Y, Kandel ES, Lausch E, Christov K, Roninson IB. Cancer Res, 1999, 59: 3761–3767
Ewald JA, Desotelle JA, Wilding G, Jarrard DF. J Natl Cancer Institute, 2010, 102: 1536–1546
Wang W, Vellaisamy K, Li G, Wu C, Ko CN, Leung CH, Ma DL. Anal Chem, 2017, 89: 11679–11684
Lim SH, Thivierge C, Nowak-Sliwinska P, Han J, van den Bergh H, Wagnieres G, Burgess K, Lee HB. J Med Chem, 2010, 53: 2865–2874
Saftig P, Sandhoff K. Nature, 2013, 502: 312–313
Shen K, Sun L, Zhang H, Xu Y, Qian X, Lu Y, Li Q, Ni L, Liu J. Cancer Lett, 2013, 333: 229–238
Galluzzi L, Bravo-San Pedro JM, Kroemer G. Nat Cell Biol, 2014, 16: 728–736
Yosef R, Pilpel N, Tokarsky-Amiel R, Biran A, Ovadya Y, Cohen S, Vadai E, Dassa L, Shahar E, Condiotti R, Ben-Porath I, Krizhanovsky V. Nat Commun, 2016, 7: 11190
Li Y, Liu Y, Fu Y, Wei T, Le Guyader L, Gao G, Liu RS, Chang YZ, Chen C. Biomaterials, 2012, 33: 402–411
Youle RJ, Strasser A. Nat Rev Mol Cell Biol, 2008, 9: 47–59
Kågedal K, Zhao M, Svensson I, Brunk UT. Biochem J, 2001, 359: 335–343
Acknowledgments
This work was supported by the National Key Research and Development Program of China (2017YFC2103502, 2017YFE0132200), the Fundamental Research Funds for the Central Universities, the National Natural Science Fundation of China (31870949, 31670973), and Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC44900).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Conflict of interest The authors declare that they have no conflict of interest.
Experimental Supporting Information
Rights and permissions
About this article
Cite this article
Gao, Z., Gao, H., Zheng, D. et al. β-galactosidase responsive AIE fluorogene for identification and removal of senescent cancer cells. Sci. China Chem. 63, 398–403 (2020). https://doi.org/10.1007/s11426-019-9659-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11426-019-9659-2