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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.


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

Show Author's information 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

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.

Keywords: metal-organic frameworks, nanoparticles, drug delivery, nanostructures, zeolitic imidazolate framework-8 (ZIF-8)

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Publication history
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Acknowledgements

Publication history

Received: 17 August 2023
Revised: 06 September 2023
Accepted: 07 September 2023
Published: 25 October 2023
Issue date: April 2024

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© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 22101029), the Beijing Natural Science Foundation (No. 2222006), the Beijing Municipal Financial Project BJAST Scholar Programs B (No. BS202001), the Beijing Municipal Financial Project BJAST Young Scholar Programs B (No. YS202202), and the Beijing Municipal Financial Project BJAST Budding Talent Program (No. 23CE-BGS-01).

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