用于光动力疗法的pH敏感性碳酸钙-二氢卟吩e6纳米粒的制备与表征

doi:10.5246/jcps.2021.11.078

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (11): 904-911.DOI: 10.5246/jcps.2021.11.078

用于光动力疗法的pH敏感性碳酸钙-二氢卟吩e6纳米粒的制备与表征

王景茹¹^,², 张爽¹^,², 李卓越¹^,², 徐美琦¹^,², 王光雪¹^,², 张烜¹^,²^,^*()

1. 北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室, 北京 100191
2. 北京大学医学部药学院药剂学系, 北京 100191

收稿日期:2021-05-19 修回日期:2021-06-20 接受日期:2021-07-14 出版日期:2021-11-28 发布日期:2021-11-28
通讯作者: 张烜
作者简介:
+ Tel.: +86-10-82805928, E-mail: xuanzhang@bjmu.edu.cn

Preparation and characterization of pH-sensitive calcium carbonate-chlorin e6 nanoparticles for photodynamic therapy

Jingru Wang¹^,², Shuang Zhang¹^,², Zhuoyue Li¹^,², Meiqi Xu¹^,², Guangxue Wang¹^,², Xuan Zhang¹^,²^,^*()

1 Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2 Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2021-05-19 Revised:2021-06-20 Accepted:2021-07-14 Online:2021-11-28 Published:2021-11-28
Contact: Xuan Zhang

摘要/Abstract

摘要：

本研究将碳酸钙纳米粒与光敏剂二氢卟吩e6(Ce6)结合构建碳酸钙-二氢卟吩e6纳米粒(CaCO₃-Ce6 NPs), 对其粒径、电位、光学性质、pH敏感性和ROS产生能力进行表征。结果表明, CaCO₃-Ce6 NPs为粒径均匀的纳米粒, 具有优良的光学特性和pH敏感性。在4T1细胞中, 660 nm激光照射下, CaCO₃-Ce6 NPs具有比Ce6更强的ROS产生能力。上述结果表明, CaCO₃-Ce6 NPs在660 nm激光照射下具有增强的光动力作用, 有望获得更强的抗肿瘤药效。

关键词: 碳酸钙纳米粒, 二氢卟吩e6, 光动力, 活性氧, pH敏感

Abstract:

In the present study, we combined CaCO₃ NPs and Ce6 to construct CaCO₃-Ce6 nanoparticles (NPs). CaCO₃-Ce6 NPs were characterized in terms of particle size, zeta potential, UV-Vis absorption spectrum, fluorescence spectrum, FTIR spectrum, and pH-responsive behavior. The reactive oxygen species (ROS) generation in vitro was measured in 4T1 cells. The results showed that CaCO₃-Ce6 NPs were uniform-sized NPs with excellent fluorescence properties and pH-responsive behavior. The ability of ROS generation by CaCO₃-Ce6 NPs was stronger compared with Ce6 in 4T1 cells because Ca²⁺ could enhance the ROS generation, which could contribute to a stronger anti-tumor effect.

Key words: Calcium carbonate nanoparticles, Chlorin e6, Photodynamic therapy, Reactive oxygen species, pH-responsive

Supporting:

王景茹, 张爽, 李卓越, 徐美琦, 王光雪, 张烜. 用于光动力疗法的pH敏感性碳酸钙-二氢卟吩e6纳米粒的制备与表征[J]. 中国药学(英文版), 2021, 30(11): 904-911.

Jingru Wang, Shuang Zhang, Zhuoyue Li, Meiqi Xu, Guangxue Wang, Xuan Zhang. Preparation and characterization of pH-sensitive calcium carbonate-chlorin e6 nanoparticles for photodynamic therapy[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(11): 904-911.

图/表 9

Figure 1. The average size (A) and zeta potential (B) of CaCO3 NPs and CaCO3-Ce6 NPs (n = 3).

Figure 2. Particle size distribution of CaCO3-Ce6 NPs.

Figure 3. Zeta potential of CaCO3-Ce6 NPs.

Figure 4. UV-Vis absorption spectra of CaCO3 NPs, Ce6 and CaCO3-Ce6 NPs.

Figure 5. Fluorescence spectra of CaCO3 NPs, Ce6 and CaCO3-Ce6 NPs (Ex: excitation spectrum; Em: Emission spectrum).

Figure 6. FTIR spectra of CaCO3 NPs, Ce6 and CaCO3-Ce6 NPs.

Figure 7. Changes in particle size of CaCO3-Ce6 NPs after incubated in PBS with different pH values at 37 °C (n = 3).

Figure 8. Fluorescence intensity of DCFH. ***P < 0.001 (n = 3).

Figure 9. (A) Confocal images of ROS generation in 4T1 tumor cells and (B) semi-quantitative analysis. *P < 0.05, ***P < 0.001.

参考文献 26

[1]	Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J. Clin. 2018, 68, 394–424.
[2]	Chen, J.M.; Fan, T.J.; Xie, Z.J.; Zeng, Q.Q.; Xue, P.; Zheng, T.T.; Chen, Y.; Luo, X.L.; Zhang, H. Advances in nanomaterials for photodynamic therapy applications: Status and challenges. Biomaterials. 2020, 237, 119827.
[3]	De Angelis, C. Side effects related to systemic cancer treatment: are we changing the Promethean experience with molecularly targeted therapies? Curr. Oncol. Tor. Ont. 2008, 15, 198–199.
[4]	Phua, S.Z.F.; Yang, G.B.; Lim, W.Q.; Verma, A.; Chen, H.Z.; Thanabalu, T.; Zhao, Y.L. Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor. ACS Nano. 2019, 13, 4742–4751.
[5]	Dolmans, D.E.; Fukumura, D.; Jain, R.K. Photodynamic therapy for cancer. Nat. Rev. Cancer. 2003, 3, 380–387.
[6]	Jiang, W.; Zhang, Z.; Wang, Q.; Dou, J.X.; Zhao, Y.Y.; Ma, Y.C.; Liu, H.R.; Xu, H.X.; Wang, Y.C. Tumor reoxygenation and blood perfusion enhanced photodynamic therapy using ultrathin graphdiyne oxide nanosheets. Nano Lett. 2019, 19, 4060–4067.
[7]	Alzeibak, R.; Mishchenko, T.A.; Shilyagina, N.Y.; Balalaeva, I.V.; Vedunova, M.V.; Krysko, D.V. Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future. J. Immunother. Cancer. 2021, 9, e001926. DOI:10.1136/jitc-2020-001926.
[8]	Zhou, H.; Ge, J.X.; Miao, Q.Q.; Zhu, R.; Wen, L.; Zeng, J.F.; Gao, M.Y. Biodegradable inorganic nanoparticles for cancer theranostics: insights into the degradation behavior. Bioconjugate Chem. 2020, 31, 315–331.
[9]	Bourquin, J.; Milosevic, A.; Hauser, D.; Lehner, R.; Blank, F.; Petri-Fink, A.; Rothen-Rutishauser, B. Biodistribution, clearance, and long-term fate of clinically relevant nanomaterials. Adv. Mater. 2018, 30, 1704307.
[10]	Arami, H.; Khandhar, A.; Liggitt, D.; Krishnan, K.M. In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles. Chem. Soc. Rev. 2015, 44, 8576–8607.
[11]	Maleki Dizaj, S.; Barzegar-Jalali, M.; Zarrintan, M.H.; Adibkia, K.; Lotfipour, F. Calcium carbonate nanoparticles as cancer drug delivery system. Expert. Opin. Drug Deliv. 2015, 12, 1649–1660.
[12]	Maleki Dizaj, S.; Sharifi, S.; Ahmadian, E.; Eftekhari, A.; Adibkia, K.; Lotfipour, F. An update on calcium carbonate nanoparticles as cancer drug/gene delivery system. Expert. Opin. Drug Deliv. 2019, 16, 331–345.
[13]	Cheng, L.; Weir, M.D.; Xu, H.H.K.; Antonucci, J.M.; Kraigsley, A.M.; Lin, N.J.; Lin-Gibson, S.; Zhou, X.D. Antibacterial amorphous calcium phosphate nanocomposites with a quaternary ammonium dimethacrylate and silver nanoparticles. Dent. Mater. 2012, 28, 561–572.
[14]	Ferreira, J.R.; Ferreira, J.R.; Padilla, R.; Urkasemsin, G.; Yoon, K.; Goeckner, K.; Hu, W.S.; Ko, C.C. Titanium-enriched hydroxyapatite-gelatin scaffolds with osteogenically differentiated progenitor cell aggregates for calvaria bone regeneration. Tissue Eng. A. 2013, 19, 1803–1816.
[15]	Huang, H.F.; Zhang, W.J.; Liu, Z.; Guo, H.Q.; Zhang, P.Y. Smart responsive-calcium carbonate nanoparticles for dual-model cancer imaging and treatment. Ultrasonics. 2020, 108, 106198.
[16]	Zhao, D.; Liu, C.J.; Zhuo, R.X.; Cheng, S.X. Alginate/CaCO₃ hybrid nanoparticles for efficient codelivery of antitumor gene and drug. Mol. Pharm. 2012, 9, 2887–2893.
[17]	Lin, T.; Zhao, X.; Zhao, S.; Yu, H.; Cao, W.; Chen, W.; Wei, H.; Guo, H. O₂^-generating MnO₂ nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia. Theranostics. 2018, 8, 990–1004.
[18]	Hoorelbeke, D.; Decrock, E.; van Haver, V.; Bock, M.D.; Leybaert, L. Calcium, a pivotal player in photodynamic therapy? Biochim. Et Biophys. Acta BBA Mol. Cell Res. 2018, 1865, 1805–1814.
[19]	Ding, X.M.; Xu, Q.Z.; Liu, F.G.; Zhou, P.K.; Gu, Y.; Zeng, J.; An, J.; Dai, W.D.; Li, X.S. Hematoporphyrin monomethyl ether photodynamic damage on HeLa cells by means of reactive oxygen species production and cytosolic free calcium concentration elevation. Cancer Lett. 2004, 216, 43–54.
[20]	Hong, X.; Jiang, F.; Kalkanis, S.N.; Zhang, Z.G.; Zhang, X.P.; Zheng, X.G.; Jiang, H.; Chopp, M. Intracellular free calcium mediates glioma cell detachment and cytotoxicity after photodynamic therapy. Lasers Med. Sci. 2009, 24, 777–786.
[21]	Görlach, A.; Bertram, K.; Hudecova, S.; Krizanova, O. Calcium and ROS: a mutual interplay. Redox Biol. 2015, 6, 260–271.
[22]	Yan, Y.; Wei, C.L.; Zhang, W.R.; Cheng, H.P.; Liu, J. Cross-talk between calcium and reactive oxygen species signaling. Acta Pharmacol. Sin. 2006, 27, 821–826.
[23]	Wu, J.L.; Wang, C.Q.; Zhuo, R.X.; Cheng, S.X. Multi-drug delivery system based on alginate/calcium carbonate hybrid nanoparticles for combination chemotherapy. Colloids Surf. B Biointerfaces. 2014, 123, 498–505.
[24]	Preisig, D.; Haid, D.; Varum, F.J.O.; Bravo, R.; Alles, R.; Huwyler, J.; Puchkov, M. Drug loading into porous calcium carbonate microparticles by solvent evaporation. Eur. J. Pharm. Biopharm. 2014, 87, 548–558.
[25]	Wang, C.; Tao, H.Q.; Cheng, L.; Liu, Z. Near-infrared light induced in vivo photodynamicS therapy of cancer based on upconversion nanoparticles. Biomaterials. 2011, 32, 6145–6154.
[26]	Yang, T.Z.; Wan, Z.H.; Liu, Z.Y.; Li, H.H.; Wang, H.; Lu, N.; Chen, Z.H.; Mei, X.F.; Ren, X.L. In situ mineralization of anticancer drug into calcium carbonate monodisperse nanospheres and their pH-responsive release property. Mater. Sci. Eng. C. 2016, 63, 384–392.

用于光动力疗法的pH敏感性碳酸钙-二氢卟吩e6纳米粒的制备与表征

Preparation and characterization of pH-sensitive calcium carbonate-chlorin e6 nanoparticles for photodynamic therapy

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