Upconversion nano-photosensitizer targeting into mitochondria for cancer apoptosis induction and cyt c fluorescence monitoring
Tóm tắt
Disruption of mitochondrial reactive oxygen species (mitoROS) plays a major role in cancer cell apoptosis. Here, we designed a core/shell-structured mitochondria-targeting upconversion-based nano-photosensitizer (TPP-UC(PS)) with a lanthanide-doped upconversion nanoparticle (UCNP) core coated by a photosensitizer (PS)-incorporated dense silica shell. Following irradiation with external near-infrared laser (NIR), TPP-UC(PS) in mitochondria caused serious mitochondrial matrix swelling for the activated upconversion-based photodynamic therapy (UC-PDT), and the mobilization of cytochrome c (cyt c) was amplified in response to the increased mitoROS. Specifically, this heme-containing cyt c could be monitored by varying TPP-UC(PS)’s upconversion luminescence signal (UCL), which may facilitate the in situ detection of cyt c for apoptosis research. As a proof of concept, our designed TPP-UC(PS) may provide significant opportunities for controlling cancer cell apoptosis under NIR stimulation and for studying apoptosis using the dynamic UCL, which is influenced by local cyt c.
Tài liệu tham khảo
Gogvadze, V. Targeting mitochondria in fighting cancer. Curr. Pharm. Des. 2011, 17, 4034–4046.
Fulda, S.; Galluzzi, L.; Kroemer, G. Targeting mitochondria for cancer therapy. Nat. Rev. Drug Discov. 2010, 9, 447–464.
Jokerst, J. V.; Gambhir, S. S. Molecular imaging with theranostic nanoparticles. Acc. Chem. Res. 2011, 44, 1050–1060.
Hu, Q. L.; Gao, M.; Feng, G. X.; Liu, B. Mitochondriatargeted cancer therapy using a light-up probe with aggregation-induced-emission characteristics. Angew. Chem., Int. Ed. 2014, 53, 14225–14229.
Petronilli, V.; Penzo, D.; Scorrano, L.; Bernardi, P.; Di Lisa, F. The mitochondrial permeability transition, release of cytochrome c and cell death. Correlation with the duration of pore openings in situ. J. Biol. Chem. 2001, 276, 12030–12034.
Dougherty, T. J.; Gomer, C. J.; Henderson, B. W.; Jori, G.; Kessel, D.; Korbelik, M.; Moan, J.; Peng, Q. Photodynamic therapy. J. Natl. Cancer Inst. 1998, 90, 889–905.
Liu, Y. Y.; Liu, Y.; Bu, W. B.; Cheng, C.; Zuo, C. J.; Xiao, Q. F.; Sun, Y.; Ni, D. L.; Zhang, C.; Liu, J. N. et al. Hypoxia induced by upconversion-based photodynamic therapy: Towards highly effective synergistic bioreductive therapy in tumors. Angew. Chem., Int. Ed. 2015, 54, 8105–8109.
Fan, W. P.; Bu, W. B.; Shen, B.; He, Q. J.; Cui, Z. W.; Liu, Y. Y.; Zheng, X. P.; Zhao, K. L.; Shi, J. L. Intelligent MnO2 nanosheets anchored with upconversion nanoprobes for concurrent pH-/H2O2-responsive UCL imaging and oxygenelevated synergetic therapy. Adv. Mater. 2015, 27, 4155–4161.
Ai, X. Z.; Ho, C. J. H.; Aw, J.; Attia, A. B. E.; Mu, J.; Wang, Y.; Wang, X. Y.; Wang, Y.; Liu, X. G.; Chen, H. B. et al. In vivo covalent cross-linking of photon-converted rareearth nanostructures for tumour localization and theranostics. Nat. Commun. 2016, 7, 10432.
Idris, N. M.; Gnanasammandhan, M. K.; Zhang, J.; Ho, P. C.; Mahendran, R.; Zhang, Y. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat. Med. 2012, 18, 1580–1585.
Toccafondi, C.; Prato, M.; Maidecchi, G.; Penco, A.; Bisio, F.; Cavalleri, O.; Canepa, M. Optical properties of yeast cytochrome c monolayer on gold: An in situ spectroscopic ellipsometry investigation. J. Colloid Interface Sci. 2011, 364, 125–132.
Ishida, M.; Dohmae, N.; Shiro, Y.; Oku, T.; Iizuka, T.; Isogai, Y. Design and synthesis of de novo cytochromes c. Biochemistry 2004, 43, 9823–9833.
Wang, X. H.; Peng, H. S.; Yang, L.; You, F. T.; Teng, F.; Hou, L. L.; Wolfbeis, O. S. Targetable phosphorescent oxygen nanosensors for the assessment of tumor mitochondrial dysfunction by monitoring the respiratory activity. Angew. Chem., Int. Ed. 2014, 53, 12471–12475.
Liu, Y. Y.; Liu, Y.; Bu, W. B.; Xiao, Q. F.; Sun, Y.; Zhao, K. L.; Fan, W. P.; Liu, J. N.; Shi, J. L. Radiation-/hypoxia-induced solid tumor metastasis and regrowth inhibited by hypoxiaspecific upconversion nanoradiosensitizer. Biomaterials 2015, 49, 1–8.
Qiao, X. F.; Zhou, J. C.; Xiao, J. W.; Wang, Y. F.; Sun, L. D.; Yan, C. H. Triple-functional core–shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro. Nanoscale 2012, 4, 4611–4623.
Shi, X. Y.; Wang, S. H.; Swanson, S. D.; Ge, S.; Cao, Z. Y.; Van Antwerp, M. E.; Landmark, K. J.; Baker, J. R., Jr. Dendrimer-functionalized shell-crosslinked iron oxide nanoparticles for in-vivo magnetic resonance imaging of tumors. Adv. Mater. 2008, 20, 1671–1678.
Wang, X. H.; Peng, H. S.; Yang, L.; You, F. T.; Teng, F.; Tang, A. W.; Zhang, F. J.; Li, X. H. Poly-L-lysine assisted synthesis of core–shell nanoparticles and conjugation with triphenylphosphonium to target mitochondria. J. Mater. Chem. B 2013, 1, 5143–5152.
Gallego, M. A.; Joseph, B.; Hemstrom, T. H.; Tamiji, S.; Mortier, L.; Kroemer, G.; Formstecher, P.; Zhivotovsky, B.; Marchetti, P. Apoptosis-inducing factor determines the chemoresistance of non-small-cell lung carcinomas. Oncogene 2004, 23, 6282–6291.
Kumar, R.; Han, J. Y.; Lim, H. J.; Ren, W. X.; Lim, J. Y.; Kim, J. H.; Kim, J. S. Mitochondrial induced and selfmonitored intrinsic apoptosis by antitumor theranostic prodrug: In vivo imaging and precise cancer treatment. J. Am. Chem. Soc. 2014, 136, 17836–17843.
Crompton, M. The mitochondrial permeability transition pore and its role in cell death. Biochem. J. 1999, 341, 233–249.
Ding, F.; Shao, Z. W.; Yang, S. H.; Wu, Q.; Gao, F.; Xiong, L. M. Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells. Apoptosis 2012, 17, 579–590.
Chen, T. T.; Tian, X.; Liu, C. L.; Ge, J.; Chu, X.; Li, Y. F. Fluorescence activation imaging of cytochrome c released from mitochondria using aptameric nanosensor. J. Am. Chem. Soc. 2015, 137, 982–989.
Konermann, L.; Douglas, D. J. Acid-induced unfolding of cytochrome c at different methanol concentrations: Electrospray ionization mass spectrometry specifically monitors changes in the tertiary structure. Biochemistry 1997, 36, 12296–12302.