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Research Article

Direct cytoplasm delivery of gold nanoparticles for real-time apoptosis detection

Qiang Li, Fengchao Wang, Jie Yang( ), Dingbin Liu( )
Research Center for Analytical Sciences, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, and Tianjin Key Laboratory of Molecular Recognition and Biosensing, College of Chemistry, Nankai University, Tianjin 300071, China
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Abstract

Gold nanoparticles (AuNPs) assembled with fluorescent peptides through Au-S bonds (pep-AuNPs) have been widely used in biomolecular detection. However, due to the endo/lysosomal trapping after the nanoprobes enter cells, the direct delivery of AuNP probes into the cytoplasm for real-time imaging remains a difficult barrier for many cytoplasm-targeting agents. Here, we prepare AuNP@gel by wrapping a multi-functional nanogel structure on the surface of a single AuNP probe by in-situ polymerization in order to directly deliver AuNP probes into the cell cytoplasm. Compared with the pep-AuNP probes, which are trapped inside lysosomes for long periods, the AuNP@gel probes use the proton-sponge effect to effectively disrupt endo/lysosomal membranes and remain in the cytoplasm. In addition, the AuNP@gel probes rapidly escape from endo/lysosomes to avoid the complex environment that interferes with the stability of the AuNP probes and the lysosomal-storage trigger the upregulation of oxidative stress into the cells. The nanogel structure enables the AuNP probes to avoid some detrimental effects and to achieve high-fidelity fluorescence signals in the cells. Compared to traditional strategies for lysosomal escape, this one-step in-situ polymerization procedure avoids the complicated modification of additional ligands and is generally applicable to peptide-, DNA-, and polymer-linked AuNP probes.

Keywords

gold nanoprobesnanogelendo/lysosomal escapereal-time imagingapoptosis detection

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References

[1]
Qian, X. M.; Peng, X. H.; Ansari, D. O.; Yin-Goen, Q.; Chen, G. Z.; Shin, D. M.; Yang, L.; Young, A. N.; Wang, M. D.; Nie, S. M. In vivo tumor targeting and spectroscopic detection with surface-enhanced raman nanoparticle tags. Nat. Biotechnol. 2008, 26, 83-90.
Google Scholar
[2]
Zhou, W.; Li, Q.; Liu, H. Q.; Yang, J.; Liu, D. B. Building electromagnetic hot spots in living cells via target-triggered nanoparticle dimerization. ACS Nano 2017, 11, 3532-3541.
Google Scholar
[3]
Jun, Y. W.; Sheikholeslami, S.; Hostetter, D. R.; Tajon, C.; Craik, C. S.; Alivisatos, A. P. Continuous imaging of plasmon rulers in live cells reveals early-stage caspase-3 activation at the single-molecule level. Proc. Natl. Acad. Sci. USA 2009, 106, 17735-17740.
Google Scholar
[4]
Zhao, X.; Yang, C. X.; Chen, L. G.; Yan, X. P. Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy. Nat. Commun. 2017, 8, 14998.
Google Scholar
[5]
Liu, Z. J.; Zhao, J.; Zhang, R. L.; Han, G. M.; Zhang, C.; Liu, B. H.; Zhang, Z. P.; Han, M. Y.; Gao, X. H. Cross-platform cancer cell identification using telomerase-specific spherical nucleic acids. ACS Nano 2018, 12, 3629-3637.
Google Scholar
[6]
Lee, S.; Cha, E. J.; Park, K.; Lee, S. Y.; Hong, J. K.; Sun, I. C.; Kim, S. Y.; Choi, K.; Kwon, I. C.; Kim, K. et al. A near-infrared-fluorescence-quenched gold-nanoparticle imaging probe for in vivo drug screening and protease activity determination. Angew. Chem., Int. Ed. 2008, 47, 2804-2807.
Google Scholar
[7]
Wang, P.; Zhang, L. M.; Zheng, W. F.; Cong, L. M.; Guo, Z. R.; Xie, Y. Z.; Wang, L.; Tang, R. B.; Feng, Q.; Hamada, Y. et al. Thermo-triggered release of crispr-cas9 system by lipid-encapsulated gold nanoparticles for tumor therapy. Angew. Chem., Int. Ed. 2018, 57, 1491-1496.
Google Scholar
[8]
Zhang, L. M.; Wang, L.; Xie, Y. Z. Y.; Wang, P.; Deng, S.; Qin, A. P.; Zhang, J. J.; Yu, X. Y.; Zheng, W. F.; Jiang, X. Y. Triple-targeting delivery of crispr/cas9 to reduce the risk of cardiovascular diseases. Angew. Chem., Int. Ed. 2019, 58, 12404-12408.
Google Scholar
[9]
Zhu, Y. X.; Jia, H. R.; Pan, G. Y.; Ulrich, N. W.; Chen, Z.; Wu, F. G. Development of a light-controlled nanoplatform for direct nuclear delivery of molecular and nanoscale materials. J. Am. Chem. Soc. 2018, 140, 4062-4070.
Google Scholar
[10]
Blanco, E.; Shen, H. F.; Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015, 33, 941-951.
Google Scholar
[11]
Le Roy, C.; Wrana, J. L. Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling. Nat. Rev. Mol. Cell Biol. 2005, 6, 112-126.
Google Scholar
[12]
Ma, W.; Fu, P.; Sun, M. Z.; Xu, L. G.; Kuang, H.; Xu, C. L. Dual quantification of micrornas and telomerase in living cells. J. Am. Chem. Soc. 2017, 139, 11752-11759.
Google Scholar
[13]
Xu, L. G.; Kuang, H.; Xu, C. L.; Ma, W.; Wang, L. B.; Kotov, N. A. Regiospecific plasmonic assemblies for in situ raman spectroscopy in live cells. J. Am. Chem. Soc. 2012, 134, 1699-1709.
Google Scholar
[14]
Hu, B.; Kong, F. P.; Gao, X. N.; Jiang, L. L.; Li, X. F.; Gao, W.; Xu, K. H.; Tang, B. Avoiding thiol compound interference: A nanoplatform based on high-fidelity Au-Se bonds for biological applications. Angew. Chem., Int. Ed. 2018, 57, 5306-5309.
Google Scholar
[15]
Liu, X. J.; Song, X. X.; Luan, D. R.; Hu, B.; Xu, K. H.; Tang, B. Real-time in situ visualizing of the sequential activation of caspase cascade using a multicolor gold-selenium bonding fluorescent nanoprobe. Anal. Chem. 2019, 91, 5994-6002.
Google Scholar
[16]
Dong, B.; Du, S. L.; Wang, C. X.; Fu, H. H.; Li, Q.; Xiao, N. N.; Yang, J.; Xue, X.; Cai, W. S.; Liu, D. B. Reversible self-assembly of nanoprobes in live cells for dynamic intracellular pH imaging. ACS Nano 2019, 13, 1421-1432.
Google Scholar
[17]
Levine, B.; Mizushima, N.; Virgin, H. W. Autophagy in immunity and inflammation. Nature 2011, 469, 323-335.
Google Scholar
[18]
Yong, T. Y.; Zhang, X. Q.; Bie, N. N.; Zhang, H. B.; Zhang, X. T.; Li, F. Y.; Hakeem, A.; Hu, J.; Gan, L.; Santos, H. A. et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat. Commun. 2019, 10, 3838.
Google Scholar
[19]
Cheng, Y. L.; Yumul, R. C.; Pun, S. H. Virus-inspired polymer for efficient in vitro and in vivo gene delivery. Angew. Chem., Int. Ed. 2016, 55, 12013-12017.
Google Scholar
[20]
Xiong, X. B.; Uludağ, H.; Lavasanifar, A. Biodegradable amphiphilic poly(ethylene oxide)-block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery. Biomaterials 2009, 30, 242-253.
Google Scholar
[21]
Sun, W. J.; Jiang, T. Y.; Lu, Y.; Reiff, M.; Mo, R.; Gu, Z. Cocoon-like self-degradable DNA nanoclew for anticancer drug delivery. J. Am. Chem. Soc. 2014, 136, 14722-14725.
Google Scholar
[22]
Theodossiou, T. A.; Goncalves, A. R.; Yannakopoulou, K.; Skarpen, E.; Berg, K. Photochemical internalization of tamoxifens transported by a “trojan-horse” nanoconjugate into breast-cancer cell lines. Angew. Chem., Int. Ed. 2015, 54, 4885-4889.
Google Scholar
[23]
Han, L.; Liu, C. Y.; Qi, H. Z.; Zhou, J. H.; Wen, J.; Wu, D.; Xu, D.; Qin, M.; Ren, J.; Wang, Q. X. et al. Systemic delivery of monoclonal antibodies to the central nervous system for brain tumor therapy. Adv. Mater. 2019, 31, 1805697.
Google Scholar
[24]
Liu, Y.; Du, J. J.; Yan, M.; Lau, M. Y.; Hu, J.; Han, H.; Yang, O. O.; Liang, S.; Wei, W.; Wang, H. et al. Biomimetic enzyme nanocomplexes and their use as antidotes and preventive measures for alcohol intoxication. Nat. Nanotechnol. 2013, 8, 187-192.
Google Scholar
[25]
Yan, M.; Du, J. J.; Gu, Z.; Liang, M.; Hu, Y. F.; Zhang, W. J.; Priceman, S.; Wu, L.; Zhou, Z. H.; Liu, Z. et al. A novel intracellular protein delivery platform based on single-protein nanocapsules. Nat. Nanotechnol. 2010, 5, 48-53.
Google Scholar
[26]
Ding, J. X.; Chen, J. J.; Gao, L. Q.; Jiang, Z. Y.; Zhang, Y.; Li, M. Q.; Xiao, Q. C.; Lee, S. S.; Chen, X. S. Engineered nanomedicines with enhanced tumor penetration. Nano Today 2019, 29, 100800.
Google Scholar
[27]
Li, Q.; Qiao, X. K.; Wang, F. C.; Li, X. J.; Yang, J.; Liu, Y.; Shi, L. Q.; Liu, D. B. Encapsulating a single nanoprobe in a multifunctional nanogel for high-fidelity imaging of caspase activity in vivo. Anal. Chem. 2019, 91, 13633-13638.
Google Scholar
[28]
Zhang, J.; Campbell, R. E.; Ting, A. Y.; Tsien, R. Y. Creating new fluorescent probes for cell biology. Nat. Rev. Mol. Cell Biol. 2002, 3, 906-918.
Google Scholar
[29]
Ma, D.; Fang, Q.; Wang, P.; Gao, R.; Wu, W. B.; Lu, T. S.; Cao, L.; Hu, X. Y.; Wang, J. S. Induction of heme oxygenase-1 by Na+-H+ exchanger 1 protein plays a crucial role in imatinib-resistant chronic myeloid leukemia cells. J. Biol. Chem. 2015, 290, 12558-12571.
Google Scholar
[30]
Guan, L. Y.; Han, B. S.; Li, Z. S.; Hua, F. Y.; Huang, F.; Wei, W.; Yang, Y.; Xu, C. M. Sodium selenite induces apoptosis by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in human acute promyelocytic leukemia NB4 cells. Apoptosis 2009, 14, 218-225.
Google Scholar
[31]
Cheng, H.; Lederer, W. J.; Cannell, M. B. Calcium sparks: Elementary events underlying excitation-contraction coupling in heart muscle. Science 1993, 262, 740-744.
Google Scholar
[32]
Shi, H. B.; Kwok, R. T. K.; Liu, J. Z.; Xing, B. Q.; Tang, B. Z.; Liu, B. Real-time monitoring of cell apoptosis and drug screening using fluorescent light-up probe with aggregation-induced emission characteristics. J. Am. Chem. Soc. 2012, 134, 17972-17981.
Google Scholar
[33]
Yuan, Y. Y.; Kwok, R. T. K.; Tang, B. Z.; Liu, B. Targeted theranostic platinum(IV) prodrug with a built-in aggregation-induced emission light-up apoptosis sensor for noninvasive early evaluation of its therapeutic responses in situ. J. Am. Chem. Soc. 2014, 136, 2546-2554.
Google Scholar
[34]
Green, D. R. The coming decade of cell death research: Five riddles. Cell 2019, 177, 1094-1107.
Google Scholar
[35]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol. 2007, 35, 495-516.
Google Scholar
[36]
Chang, H. Y.; Yang, X. Proteases for cell suicide: Functions and regulation of caspases. Microbiol. Mol. Biol. Rev. 2000, 64, 821-846.
Google Scholar
[37]
Yun, C. S.; Javier, A.; Jennings, T.; Fisher, M.; Hira, S.; Peterson, S.; Hopkins, B.; Reich, N. O.; Strouse, G. F. Nanometal surface energy transfer in optical rulers, breaking the FRET barrier. J. Am. Chem. Soc. 2005, 127, 3115-3119.
Google Scholar
[38]
Zhao, F.; Zhao, Y.; Liu, Y.; Chang, X. L.; Chen, C. Y.; Zhao, Y. L. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 2011, 7, 1322-1337.
Google Scholar
[39]
Paglin, S.; Lee, N. Y.; Nakar, C.; Fitzgerald, M.; Plotkin, J.; Deuel, B.; Hackett, N.; McMahill, M.; Sphicas, E.; Lampen, N. et al. Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated mcf-7 cells. Cancer Res. 2005, 65, 11061-11070.
Google Scholar
[40]
Mizushima, N.; Levine, B.; Cuervo, A. M.; Klionsky, D. J. Autophagy fights disease through cellular self-digestion. Nature 2008, 451, 1069-1075.
Google Scholar
[41]
Mizushima, N.; Yoshimori, T.; Levine, B. Methods in mammalian autophagy research. Cell 2010, 140, 313-326.
Google Scholar
[42]
Li, W. J.; Chen, Y.; Nie, S. P.; Xie, M. Y.; He, M.; Zhang, S. S.; Zhu, K. X. Ganoderma atrum polysaccharide induces anti-tumor activity via the mitochondrial apoptotic pathway related to activation of host immune response. J. Cell Biochem. 2011, 112, 860-871.
Google Scholar
[43]
Sun, I. C.; Lee, S.; Koo, H.; Kwon, I. C.; Choi, K.; Ahn, C. H.; Kim, K. Caspase sensitive gold nanoparticle for apoptosis imaging in live cells. Bioconjugate Chem. 2010, 21, 1939-1942.
Google Scholar
[44]
Pan, S.; Berk, B. C. Glutathiolation regulates tumor necrosis factor-α-induced caspase-3 cleavage and apoptosis: Key role for glutaredoxin in the death pathway. Circ. Res. 2007, 100, 213-219.
Google Scholar
[45]
Walkey, C. D.; Olsen, J. B.; Guo, H. B.; Emili, A.; Chan, W. C. W. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J. Am. Chem. Soc. 2012, 134, 2139-2147.
Google Scholar
[46]
Ye, D. J.; Shuhendler, A. J.; Cui, L. N.; Tong, L.; Tee, S. S.; Tikhomirov, G.; Felsher, D. W.; Rao, J. H. Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo. Nat. Chem. 2014, 6, 519-526.
Google Scholar
Nano Research
Volume 13 Issue 3,
March 2020
Pages 853-860
DOI: 10.1007/s12274-020-2707-y
Cite this article:
Li Q, Wang F, Yang J, et al. Direct cytoplasm delivery of gold nanoparticles for real-time apoptosis detection. Nano Research, 2020, 13(3): 853-860. https://doi.org/10.1007/s12274-020-2707-y
Topics:
Cell death Fiber optic sensorsFluorescenceGold nanoparticlesMetal nanoparticlesNanoprobesNanostructured materialsPeptidesProbes

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Received: 20 December 2019
Revised: 07 February 2020
Accepted: 09 February 2020
Published: 06 March 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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