文献类型：期刊文献

英文题名：Bioengineered "Molecular Glue"-Mediated Tumor-Specific Cascade Nanoreactors with Self-Destruction Ability for Enhanced Precise Starvation/Chemosynergistic Tumor Therapy

作者：Zhang, Qi[1];Xuan, Qize[1];Wang, Chen[2];Shi, Chongli[2];Wang, Xiaoli[1];Ma, Tonghao[1];Zhang, Wei[1];Li, Hui[2];Wang, Ping[3];Chen, Chao[1,2]

机构：[1]East China Univ Sci & Technol, Biomed Nanotechnol Ctr, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China;[3]Univ Minnesota, Dept Bioprod & Biosyst Engn, St Paul, MN 55108 USA

年份：2023

卷号：15

期号：35

起止页码：41271

外文期刊名：ACS APPLIED MATERIALS & INTERFACES

收录：;EI(收录号：20233714702771);WOS:【SCI-EXPANDED(收录号:WOS:001063619500001)】；

基金：This work was sponsored by the National Natural Science Foundation of China (Nos. 21908059 and 42125706), the Natural Science Foundation of Shanghai (22ZR1415400), the Shanghai Rising-Star Program (23QC1400500), the National Key Research and Development Plan of China (2019YFC1805800), the Foundation of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences (Grant No. GZKF202031), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. All animal experiments were conducted in accordance with the Chinese legislation on the Use and Care of Research Animals (Document No. 55, 2001) and institutional guidelines for the Care and Use of Laboratory Animals established by the East China University of Science and Technology Animal Studies Committee, and this committee approved the experiments. The authors thank the Research Centre of Analysis and Test of East China University of Science and Technology for the sample characterization. They also thank the support from Zhang Jiangshu Excellent Doctoral Program of East China University of Science and Technology.

语种：英文

外文关键词：materials-based synthetic biotechnology strategy; orientedand ordered assembly; materials-binding peptide; starvation/chemosynergistic therapy; nontoxic precise targeting

摘要：The ordered and directed functionalization of targeting elements on the surface of nanomaterials for precise tumor therapy remains a challenge. To address the above problem, herein, we adopted a materials-based synthetic biotechnology strategy to fabricate a bioengineered fusion protein of materials-binding peptides and targeting elements, which can serve as a "molecular glue" to achieve a directional and organized assembly of targeting biological macromolecules on the surface of nanocarriers. The hypoxia microenvironment of solid tumors inspired the rapid development of starvation/chemosynergistic therapy; however, the unsatisfied spatiotemporal specific performance hindered its further development in precise tumor therapy. As a proof of concept, a bioengineered fusion protein containing a dendritic mesoporous silicon (DMSN)-binding peptide, and a tumor-targeted and acidity-decomposable ferritin heavy chain 1 (FTH1), was constructed by fusion expression and further assembled on the surface of DMSN companying with the insertion of hypoxia-activated prodrug tirapazamine (TPZ) and glucose oxidase (GOX) to establish a nanoreactor for precise starvation/chemosynergistic tumor therapy. In this context, the as-prepared therapeutic nanoreactors revealed obvious tumor-specific accumulation and an endocytosis effect. Next, the acidic tumor microenvironment triggered the structural collapse of FTH1 and the subsequent release of GOX and TPZ, in which GOX-mediated catalysis cut off the nutrition supply to realize starvation therapy based on the consumption of endogenous glucose and further provided an exacerbated hypoxia environment for TPZ in situ activation to initiate tumor chemotherapy. More significantly, the presence of "molecular glue" elevated the tumor-targeting capacity of nanoreactors and further enhanced the starvation/chemosynergistic therapeutic effect remarkably, suggesting that such a strategy provided a solution for the functionality of nanomaterials and facilitated the design of novel targeting nanomedicines. Overall, this study highlights materials-binding peptides as a new type of "molecular glue" and opens new avenues for designing and exploring active biological materials for biological functions and applications.