纳米反应器
提拉帕扎明
纳米载体
纳米技术
葡萄糖氧化酶
肿瘤微环境
肿瘤缺氧
材料科学
生物物理学
化学
生物化学
药物输送
癌症研究
生物
纳米颗粒
肿瘤细胞
细胞毒性
医学
体外
内科学
生物传感器
放射治疗
作者
Qi Zhang,Qize Xuan,Wang Chen,Chongli Shi,Xiaoli Wang,Tonghao Ma,Wei Zhang,Hui Li,Píng Wang,Chao Chen
标识
DOI:10.1021/acsami.3c06871
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.
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