Volume 6, Issue 3 2101391
Research Article

Cell-Selective Encapsulation within Metal–Organic Framework Shells via Precursor-Functionalized Aptamer Identification for Whole-Cell Cancer Vaccine

Huihui Yang

Huihui Yang

Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument, School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, 518107 China

School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China

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Yanfei Zhang

Yanfei Zhang

School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China

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Leli Zeng

Leli Zeng

Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107 China

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Wen Yin

Wen Yin

School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China

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Yuzhi Xu

Corresponding Author

Yuzhi Xu

Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107 China

E-mail: [email protected]; [email protected]; [email protected]

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Jun Chen

Jun Chen

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515 China

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Si-Yang Liu

Corresponding Author

Si-Yang Liu

Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument, School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, 518107 China

E-mail: [email protected]; [email protected]; [email protected]

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Xiaoyong Zou

Xiaoyong Zou

School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China

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Zhiyu He

Zhiyu He

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, 266100 China

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Zong Dai

Corresponding Author

Zong Dai

Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument, School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, 518107 China

E-mail: [email protected]; [email protected]; [email protected]

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First published: 02 February 2022
Citations: 6

Abstract

Single-cell encapsulation is an emerging technology to endow cells with various functions, of which developing new applications in vivo is in high demand. Currently, metal–organic frameworks (MOFs) that are used as nanometric shells to coat living cells, however, have not realized cell-selective encapsulation. Here, a biocompatible and selective cell encapsulation strategy based on precursor-functionalized nucleolin aptamer and in situ MOF mineralization on the aptamer-identified cancer cell surface are developed. After MOF coating, the encapsulated cancer cells undergo immunogenic cell death, which is found associated with the changed cell stiffness (indicated by Young's modulus). The immunogenic dead cancer cells are used as whole-cell cancer vaccines (WCCVs), forming the integral WCCV-in-shell structure with enhanced immunogenicity ascribing from the surface-exposed calreticulin to promote dendritic cell recruitment, antigen presentation, and T-cell activation. The major activation pathways in the immune response are identified including tumor necrosis factor signaling pathway, cytokine–cytokine receptor interaction, and Toll-like receptor signaling pathway, suggesting the potential adjuvant effect of the MOF shells. After vaccination, WCCV-in-shell shows much better tumor immunoprophylaxis than either the imperfectly coated cancer cells or the traditional WCCV. This strategy is promising for the universal and facile development of novel whole-cell vaccines.

Conflict of Interest

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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