AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Article Link
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

A novel structure of ultra-high-loading small molecules-encapsulated ZIF-8 colloid particles

Pengfei Duan1Yunhe An1Xiaoxiao Wei1Yanjie Tian1Di Guan1Xiangwen Liu1( )Lanqun Mao1,2( )
Institute of Analysis and Testing, Beijing Academy of Science and Technology (Beijing Center for Physical and Chemical Analysis), Beijing 100089, China
College of Chemistry, Beijing Normal University, Beijing 100875, China
Show Author Information

Graphical Abstract

Drug-encapsulated drug delivery system (DDS) with a 90% ultra-high loading has been synthesized to greatly improve DDS’s safety in cancer treatment. Cytotoxicity tests and in vivo antitumor tests have verified that the as-synthesized DOX@ZIF-8 is safe and has a consistent or even slightly more desired efficacy with free DOX.

Abstract

The safety of nanoparticle-based drug delivery systems (DDSs) for cancer treatment is still a challenge, restricted by the intrinsic cytotoxicity of drug carriers and leakage of loaded drug. Here, we propose a novel nanocarrier’s cytotoxicity avoidance strategy by synthesizing an encapsulation core–shell structure of zeolitic imidazolate framework-8 (ZIF-8)-based colloid particles (CPs) with an amorphous ZIF-8 skin. This encapsulation structure achieves an ultra-high loading rate (LR) of 90% (i.e., 9 mg doxorubicin (DOX) per 1 mg ZIF-8) for DOX and the protection of DOX from leaking. Notably, to deliver unit-dose drug, this ultra-high LR of 90% significantly reduces the usage of ZIF-8 to 1.2% (2 orders of magnitude) compared to that of DOX@ZIF-8 with a 10% LR, in which cytotoxicity of ZIF-8 could well below the safety limit and then be relatively ignored. Safety, drug delivery efficacy, scale-up ability, and universality of this encapsulation structure have been further verified. Our findings suggest the great potential of this ZIF-8-based encapsulation core–shell structure in the field of drug delivery.

Electronic Supplementary Material

Download File(s)
12274_2023_6172_MOESM1_ESM.pdf (4.6 MB)

References

[1]

Ringsdorf, H. Structure and properties of pharmacologically active polymers. J. Polym. Sci. Polym. Symp. 1975, 51, 135–153.

[2]

Soppimath, K. S.; Aminabhavi, T. M.; Kulkarni, A. R.; Rudzinski, W. E. Biodegradable polymeric nanoparticles as drug delivery devices. J. Controlled Release 2001, 70, 1–20.

[3]

Xu, L. N.; Chai, J. S.; Wang, Y.; Zhao, X. Z.; Guo, D. S.; Shi, L. Q.; Zhang, Z. Z.; Liu, Y. Calixarene-integrated nano-drug delivery system for tumor-targeted delivery and tracking of anti-cancer drugs in vivo. Nano Res. 2022, 15, 7295–7303.

[4]

Kakemi, K.; Arita, T.; Muranishi, S. Absorption and excretion of drugs. XXVII. Effect of nonionic surface-active agents on rectal absorption of sulfonamides. Chem. Pharm. Bull. 1965, 13, 976–985.

[5]

Gaucher, G.; Dufresne, M. H.; Sant, V. P.; Kang, N.; Maysinger, D.; Leroux, J. C. Block copolymer micelles: Preparation, characterization and application in drug delivery. J. Controlled Release 2005, 109, 169–188.

[6]

Gregoriadis, G. The carrier potential of liposomes in biology and medicine: (First of two parts). N. Engl. J. Med. 1976, 295, 704–710.

[7]

Gregoriadis, G. The carrier potential of liposomes in biology and medicine: (Second of two parts). N. Engl. J. Med. 1976, 295, 765–770.

[8]

Wang, M.; Zuris, J. A.; Meng, F. T.; Rees, H.; Sun, S.; Deng, P.; Han, Y.; Gao, X.; Pouli, D.; Wu, Q. et al. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles. Proc. Natl. Acad. Sci. USA 2016, 113, 2868–2873.

[9]

Horcajada, P.; Serre, C.; Vallet-Regí, M.; Sebban, M.; Taulelle, F.; Férey, G. Metal-organic frameworks as efficient materials for drug delivery. Angew. Chem. 2006, 118, 6120–6124.

[10]

Horcajada, P.; Chalati, T.; Serre, C.; Gillet, B.; Sebrie, C.; Baati, T.; Eubank, J. F.; Heurtaux, D.; Clayette, P.; Kreuz, C. et al. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nat. Mater. 2010, 9, 172–178.

[11]

Jiang, S.; Liu, C. C.; He, Q. J.; Dang, K.; Zhang, W. W.; Tian, Y. Porphyrin-based metal-organic framework nanocrystals for combination of immune and sonodynamic therapy. Nano Res. 2023, 16, 9633–9641.

[12]
Chen, Y.; Tian, Q.; Wang, H. Y.; Ma, R. N.; Han, R. T.; Wang, Y.; Ge, H. B.; Ren, Y. J.; Yang, R.; Yang, H. M. et al. A manganese-based metal-organic framework as a cold-adapted nanozyme. Adv. Mater., in press, https://doi.org/10.1002/adma.202206421.
[13]

Huxford, R. C.; Della Rocca, J.; Lin, W. B. Metal-organic frameworks as potential drug carriers. Curr. Opin. Chem. Biol. 2010, 14, 262–268.

[14]

Liu, D.; Yang, F.; Xiong, F.; Gu, N. The smart drug delivery system and its clinical potential. Theranostics 2016, 6, 1306–1323.

[15]

Liang, M. M.; Fan, K. L.; Zhou, M.; Duan, D. M.; Zheng, J. Y.; Yang, D. L.; Feng, J.; Yan, X. Y. H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection. Proc. Natl. Acad. Sci. USA 2014, 111, 14900–14905.

[16]

Gu, C. Y.; Yang, S. Y.; Liu, X. S.; Jin, Y.; Yu, Y.; Lu, L. J. A biomimetic adipocyte mesenchymal stem cell membrane-encapsulated drug delivery system for the treatment of rheumatoid arthritis. Nano Res. 2023, 16, 11401–11410.

[17]

Lewinski, N.; Colvin, V.; Drezek, R. Cytotoxicity of nanoparticles. Small 2008, 4, 26–49.

[18]

Tacar, O.; Sriamornsak, P.; Dass, C. R. Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. J. Pharm. Pharmacol. 2013, 65, 157–170.

[19]

Zhang, J. L.; Cheng, D. F.; He, J. Y.; Hong, J. J.; Yuan, C.; Liang, M. M. Cargo loading within ferritin nanocages in preparation for tumor-targeted delivery. Nat. Protoc. 2021, 16, 4878–4896.

[20]

Allen, T. M.; Cullis, P. R. Liposomal drug delivery systems: From concept to clinical applications. Adv. Drug Deliv. Rev. 2013, 65, 36–48.

[21]

Akbarzadeh, A.; Rezaei-Sadabady, R.; Davaran, S.; Joo, S. W.; Zarghami, N.; Hanifehpour, Y.; Samiei, M.; Kouhi, M.; Nejati-Koshki, K. Liposome: Classification, preparation, and applications. Nanoscale Res. Lett. 2013, 8, 102.

[22]

Samad, A.; Sultana, Y.; Aqil, M. Liposomal drug delivery systems: An update review. Curr. Drug Deliv. 2007, 4, 297–305.

[23]

Sharma, A.; Sharma, U. S. Liposomes in drug delivery: Progress and limitations. Int. J. Pharm. 1997, 154, 123–140.

[24]

Park, K. S.; Ni, Z.; Côté, A. P.; Choi, J. Y.; Huang, R.; Uribe-Romo, F. J.; Chae, H. K.; O'Keeffe, M.; Yaghi, O. M. Exceptional chemical and thermal stability of zeolitic imidazolate frameworks. Proc. Natl. Acad. Sci. USA 2006, 103, 10186–10191.

[25]

Ferrari, M. Cancer nanotechnology: Opportunities and challenges. Nat. Rev. Cancer 2005, 5, 161–171.

[26]

Jiang, S.; He, Q. J.; Li, C. C.; Dang, K.; Ye, L.; Zhang, W. W.; Tian, Y. Employing the thiol-ene click reaction via metal-organic frameworks for integrated sonodynamic-starvation therapy as an oncology treatment. Sci. China Mater. 2022, 65, 1112–1121.

[27]

Sun, C. Y.; Qin, C.; Wang, X. L.; Yang, G. S.; Shao, K. Z.; Lan, Y. Q.; Su, Z. M.; Huang, P.; Wang, C. G.; Wang, E. B. Zeolitic imidazolate framework-8 as efficient pH-sensitive drug delivery vehicle. Dalton Trans. 2012, 41, 6906–6909.

[28]

Low, J. J.; Benin, A. I.; Jakubczak, P.; Abrahamian, J. F.; Faheem, S. A.; Willis, R. R. Virtual high throughput screening confirmed experimentally: Porous coordination polymer hydration. J. Am. Chem. Soc. 2009, 131, 15834–15842.

[29]

Xin, Y.; Wang, J. J.; Wu, Y. H.; Li, Q. Q.; Dong, M. Y.; Liu, C.; He, Q. J.; Wang, R. F.; Wang, D.; Jiang, S. et al. Identification of nanog as a novel inhibitor of Rad51. Cell Death Dis. 2022, 13, 193.

[30]

Yang, Y. X.; Sun, B. J.; Zuo, S. Y.; Li, X. M.; Zhou, S.; Li, L. X.; Luo, C.; Liu, H. Z.; Cheng, M. S.; Wang, Y. J. et al. Trisulfide bond-mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity. Sci. Adv. 2020, 6, eabc1725.

[31]

Barenholz, Y. Doxil®-the first FDA-approved nano-drug: Lessons learned. J. Controlled Release 2012, 160, 117–134.

[32]

Zheng, H. Q.; Zhang, Y. N.; Liu, L. F.; Wan, W.; Guo, P.; Nyström, A. M.; Zou, X. D. One-pot synthesis of metal-organic frameworks with encapsulated target molecules and their applications for controlled drug delivery. J. Am. Chem. Soc. 2016, 138, 962–968.

[33]

Li, Y. T.; Jin, J.; Wang, D. W.; Lv, J. W.; Hou, K.; Liu, Y. L.; Chen, C. Y.; Tang, Z. Y. Coordination-responsive drug release inside gold nanorod@metal-organic framework core–shell nanostructures for near-infrared-induced synergistic chemo-photothermal therapy. Nano Res. 2018, 11, 3294–3305.

[34]

Wang, Y.; Yan, J. H.; Wen, N. C.; Xiong, H. J.; Cai, S. D.; He, Q. Y.; Hu, Y. Q.; Peng, D. M.; Liu, Z. B.; Liu, Y. F. Metal-organic frameworks for stimuli-responsive drug delivery. Biomaterials 2020, 230, 119619.

[35]

Wu, Q.; Niu, M.; Chen, X. W.; Tan, L. F.; Fu, C. H.; Ren, X. L.; Ren, J.; Li, L. F.; Xu, K.; Zhong, H. S. et al. Biocompatible and biodegradable zeolitic imidazolate framework/polydopamine nanocarriers for dual stimulus triggered tumor thermo-chemotherapy. Biomaterials 2018, 162, 132–143.

[36]

Zhang, Z. Y.; Xu, Y. D.; Ma, Y. Y.; Qiu, L. L.; Wang, Y.; Kong, J. L.; Xiong, H. M. Biodegradable ZnO@polymer core–shell nanocarriers: pH-triggered release of doxorubicin in vitro. Angew. Chem., Int. Ed. 2013, 52, 4127–4131.

[37]

Jahn, A.; Vreeland, W. N.; DeVoe, D. L.; Locascio, L. E.; Gaitan, M. Microfluidic directed formation of liposomes of controlled size. Langmuir 2007, 23, 6289–6293.

[38]

Wang, M.; Alberti, K.; Sun, S.; Arellano, C. L.; Xu, Q. B. Combinatorially designed lipid-like nanoparticles for intracellular delivery of cytotoxic protein for cancer therapy. Angew. Chem., Int. Ed. 2014, 53, 2893–2898.

[39]

Doonan, C.; Riccò, R.; Liang, K.; Bradshaw, D.; Falcaro, P. Metal-organic frameworks at the biointerface: Synthetic strategies and applications. Acc. Chem. Res. 2017, 50, 1423–1432.

[40]

Ameloot, R.; Vermoortele, F.; Vanhove, W.; Roeffaers, M. B. J.; Sels, B. F.; De Vos, D. E. Interfacial synthesis of hollow metal-organic framework capsules demonstrating selective permeability. Nat. Chem. 2011, 3, 382–387.

[41]

Jeong, G. Y.; Ricco, R.; Liang, K.; Ludwig, J.; Kim, J. O.; Falcaro, P.; Kim, D. P. Bioactive MIL-88A framework hollow spheres via interfacial reaction in-droplet microfluidics for enzyme and nanoparticle encapsulation. Chem. Mater. 2015, 27, 7903–7909.

[42]

Liu, X. W.; Chee, S. W.; Raj, S.; Sawczyk, M.; Král, P.; Mirsaidov, U. Three-step nucleation of metal-organic framework nanocrystals. Proc. Natl. Acad. Sci. USA 2021, 118, e2008880118.

[43]

Pan, Y. C.; Heryadi, D.; Zhou, F.; Zhao, L.; Lestari, G.; Su, H. B.; Lai, Z. P. Tuning the crystal morphology and size of zeolitic imidazolate framework-8 in aqueous solution by surfactants. CrystEngComm 2011, 13, 6937–6940.

[44]

Zhu, Y. H.; Ciston, J.; Zheng, B.; Miao, X. H.; Czarnik, C.; Pan, Y. C.; Sougrat, R.; Lai, Z. P.; Hsiung, C. E.; Yao, K. X. et al. Unravelling surface and interfacial structures of a metal-organic framework by transmission electron microscopy. Nat. Mater. 2017, 16, 532–536.

[45]
Hu, Y.; Kazemian, H.; Rohani, S.; Huang, Y. N.; Song, Y. In situ high pressure study of ZIF-8 by FTIR spectroscopy. Chem. Commun. 2011 , 47, 12694–12696.
[46]

Abednejad, A.; Ghaee, A.; Nourmohammadi, J.; Mehrizi, A. A. Hyaluronic acid/carboxylated zeolitic imidazolate framework film with improved mechanical and antibacterial properties. Carbohydr. Polym. 2019, 222, 115033.

[47]

Zhou, Y.; Zhou, L.; Zhang, X. H.; Chen, Y. L. Preparation of zeolitic imidazolate framework-8/graphene oxide composites with enhanced VOCs adsorption capacity. Microporous Mesoporous Mater. 2016, 225, 488–493.

[48]

Ran, J. B.; Zeng, H.; Cai, J.; Jiang, P.; Yan, P.; Zheng, L. Y.; Bai, Y.; Shen, X. Y.; Shi, B.; Tong, H. Rational design of a stable, effective, and sustained dexamethasone delivery platform on a titanium implant: An innovative application of metal organic frameworks in bone implants. Chem. Eng. J. 2018, 333, 20–33.

[49]

Jian, M. P.; Liu, B.; Zhang, G. S.; Liu, R. P.; Zhang, X. W. Adsorptive removal of arsenic from aqueous solution by zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. Colloids Surf. A Physicochem. Eng. Asp. 2015, 465, 67–76.

[50]

Pan, Y. C.; Liu, Y. Y.; Zeng, G. F.; Zhao, L.; Lai, Z. P. Rapid synthesis of zeolitic imidazolate framework-8 (ZIF-8) nanocrystals in an aqueous system. Chem. Commun. 2011, 47, 2071–2073.

[51]

Chauhan, A.; Chauhan, P. Powder XRD technique and its applications in science and technology. J. Anal. Bioanal. Tech. 2014, 5, 1–5.

[52]

Ryczkowski, J. IR spectroscopy in catalysis. Catal. Today 2001, 68, 263–381.

[53]

Saliba, D.; Ammar, M.; Rammal, M.; Al-Ghoul, M.; Hmadeh, M. Crystal growth of ZIF-8, ZIF-67, and their mixed-metal derivatives. J. Am. Chem. Soc. 2018, 140, 1812–1823.

[54]

Lee, Y. R.; Jang, M. S.; Cho, H. Y.; Kwon, H. J.; Kim, S.; Ahn, W. S. ZIF-8: A comparison of synthesis methods. Chem. Eng. J. 2015, 271, 276–280.

[55]

Stubbs, M.; McSheehy, P. M. J.; Griffiths, J. R.; Bashford, C. L. Causes and consequences of tumour acidity and implications for treatment. Mol. Med. Today 2000, 6, 15–19.

[56]

Ren, H.; Zhang, L. Y.; An, J. P.; Wang, T. T.; Li, L.; Si, X. Y.; He, L.; Wu, X. T.; Wang, C. G.; Su, Z. M. Polyacrylic acid@zeolitic imidazolate framework-8 nanoparticles with ultrahigh drug loading capability for pH-sensitive drug release. Chem. Commun. 2014, 50, 1000–1002.

[57]

Zhou, K. J.; Liu, H. M.; Zhang, S. R.; Huang, X. N.; Wang, Y. G.; Huang, G.; Sumer, B. D.; Gao, J. M. Multicolored pH-tunable and activatable fluorescence nanoplatform responsive to physiologic pH stimuli. J. Am. Chem. Soc. 2012, 134, 7803–7811.

[58]

Abdelhamid, H. N. Zeolitic imidazolate frameworks (ZIF-8) for biomedical applications: A review. Curr. Med. Chem. 2021, 28, 7023–7075.

[59]
Liu, C. C.; Li, C. C.; Jiang, S.; Zhang, C.; Tian, Y. pH-responsive hollow Fe-gallic acid coordination polymer for multimodal synergistic-therapy and MRI of cancer. Nanoscale Adv. 2022 , 4, 173–181.
[60]

Vallet-Regí, M.; Balas, F.; Arcos, D. Mesoporous materials for drug delivery. Angew. Chem., Int. Ed. 2007, 46, 7548–7558.

[61]
Liu, J.; Huang, Y. R.; Kumar, A.; Tan, A.; Jin, S. B.; Mozhi, A.; Liang, X. J. pH-sensitive nano-systems for drug delivery in cancer therapy. Biotechnol. Adv. 2014 , 32, 693–710.
[62]

Hoop, M.; Walde, C. F.; Riccò, R.; Mushtaq, F.; Terzopoulou, A.; Chen, X. Z.; deMello, A. J.; Doonan, C. J.; Falcaro, P.; Nelson, B. J. et al. Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications. Appl. Mater. Today 2018, 11, 13–21.

[63]

Lian, T. S.; Ho, R. J. Y. Trends and developments in liposome drug delivery systems. J. Pharm. Sci. 2001, 90, 667–680.

[64]

Zhang, H.; Zhang, L.; Cao, Z. B.; Cheong, S.; Boyer, C.; Wang, Z. G.; Yun, S. L. J.; Amal, R.; Gu, Z. Two-dimensional ultra-thin nanosheets with extraordinarily high drug loading and long blood circulation for cancer therapy. Small 2022, 18, 2200299.

[65]

Yang, G. Z.; Liu, Y.; Wang, H. F.; Wilson, R.; Hui, Y.; Yu, L.; Wibowo, D.; Zhang, C.; Whittaker, A. K.; Middelberg, A. P. J. et al. Bioinspired core–shell nanoparticles for hydrophobic drug delivery. Angew. Chem. 2019, 131, 14495–14502.

[66]
Li, L. L.; Tang, F. Q.; Liu, H. Y.; Liu, T. L.; Hao, N. J.; Chen, D.; Teng, X.; He, J. Q. In vivo delivery of silica nanorattle encapsulated docetaxel for liver cancer therapy with low toxicity and high efficacy. ACS Nano 2010 , 4, 6874–6882.
[67]

Lei, Z. T.; Tang, Q. J.; Ju, Y. S.; Lin, Y. H.; Bai, X. W.; Luo, H. P.; Tong, Z. Z. Block copolymer@ZIF-8 nanocomposites as a pH-responsive multi-steps release system for controlled drug delivery. J. Biomater. Sci. Polym. Ed. 2020, 31, 695–711.

[68]

Cheng, C.; Li, C.; Zhu, X. L.; Han, W.; Li, J. H.; Lv, Y. Doxorubicin-loaded Fe3O4-ZIF-8 nano-composites for hepatocellular carcinoma therapy. J. Biomater. Appl. 2019, 33, 1373–1381.

[69]

Bi, J.; Lu, Y.; Dong, Y. S.; Gao, P. Synthesis of folic acid-modified DOX@ZIF-8 nanoparticles for targeted therapy of liver cancer. J. Nanomater. 2018, 2018, 1357812.

[70]

Ogata, A. F.; Rakowski, A. M.; Carpenter, B. P.; Fishman, D. A.; Merham, J. G.; Hurst, P. J.; Patterson, J. P. Direct observation of amorphous precursor phases in the nucleation of protein-metal-organic frameworks. J. Am. Chem. Soc. 2020, 142, 1433–1442.

[71]

de J Velásquez-Hernández, M.; Ricco, R.; Carraro, F.; Limpoco, F. T.; Linares-Moreau, M.; Leitner, E.; Wiltsche, H.; Rattenberger, J.; Schröttner, H.; Frühwirt, P. et al. Degradation of ZIF-8 in phosphate buffered saline media. CrystEngComm 2019, 21, 4538–4544.

[72]

Suchý, T.; Bartoš, M.; Sedláček, R.; Šupová, M.; Žaloudková, M.; Martynková, G. S.; Foltán, R. Various simulated body fluids lead to significant differences in collagen tissue engineering scaffolds. Materials 2021, 14, 4388.

Nano Research
Pages 2929-2940
Cite this article:
Duan P, An Y, Wei X, et al. A novel structure of ultra-high-loading small molecules-encapsulated ZIF-8 colloid particles. Nano Research, 2024, 17(4): 2929-2940. https://doi.org/10.1007/s12274-023-6172-2
Topics:

1996

Views

1

Crossref

1

Web of Science

1

Scopus

0

CSCD

Altmetrics

Received: 17 August 2023
Revised: 06 September 2023
Accepted: 07 September 2023
Published: 25 October 2023
© Tsinghua University Press 2023
Return