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Research Article

Nanovoid-confinement and click-activated nanoreactor for synchronous delivery of prodrug pairs and precise photodynamic therapy

Peng Wang1,§, Fang Zhou1,§, Xia Yin1( ), Qingji Xie2, Guosheng Song1( ), Xiao-Bing Zhang1
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
Key Laboratory of Chemical Biology and Traditional Chinese Medicine (Hunan Normal University), Ministry of Education, Changsha 410082, China

§ Peng Wang and Fang Zhou contributed equally to this work.

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Graphical Abstract

The nanovoid-confinement and click-activated (NCCA) nanoreactor is de novo developed for overcoming the space-time dislocation of bioorthogonal reagents. The NCCA nanoreactor utilized the nanoconfined bioorthogonal reactions in defined tetrazine-based covalent organic framework (COF) cages to boost the collision probability of bioorthogonal prodrug with tetrazine triggers, resulting in higher-efficiency photodynamic therapy (PDT) in vivo.

Abstract

Bioorthogonal cleavage reaction-triggered prodrug activation by the pretargeted methods can achieve accurate cancer therapy. However, the click and release efficiency of these methods in vivo is limited by the space-time dislocation of bioorthogonal prodrug-trigger pairs within the tumor area, caused by their asynchronous administration and inconsistent accumulation for most delivery systems. We herein created a nanovoid-confinement and click-activated (NCCA) core–shell nanoreactor by incorporating prodrugs within zeolitic imidazolate framework-90 (ZIF-90) as core and coating tetrazine-based covalent organic framework (COF) as shell. After surface modification of aptamer polymer, the NCCA nanoreactor enabled the sufficient delivery of photodynamic prodrugs within tumor. Notably, the core of ZIF-90 was decomposed by tumor acidic environment, inducing the high-efficiency activation of photodynamic prodrugs via nanoconfined bioorthogonal reaction with tetrazine-based COF shell. As a result, such photodynamic agents are efficiently and safely accumulated into tumor and specifically activated for precise photodynamic therapy of cancer cells and tumor bearing mice with minimizing toxic side effect. Taken together, such NCCA nanoreactor clearly demonstrates the critical feasibility to realize the synchronous delivery of both prodrugs and triggers for precise treatment, which most of delivery systems are not able to afford.

Keywords

nanoreactorcovalent organic frameworkbioorthogonal reactionprodrugphotodynamic therapy

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Nano Research
Volume 15 Issue 10,
October 2022
Pages 9264-9273
DOI: 10.1007/s12274-022-4615-9
Cite this article:
Wang P, Zhou F, Yin X, et al. Nanovoid-confinement and click-activated nanoreactor for synchronous delivery of prodrug pairs and precise photodynamic therapy. Nano Research, 2022, 15(10): 9264-9273. https://doi.org/10.1007/s12274-022-4615-9
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Received: 28 March 2022
Revised: 01 June 2022
Accepted: 03 June 2022
Published: 02 July 2022
© Tsinghua University Press 2022
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