School of Life Science, Beijing Institute of Technology, No. 5 South Zhong Guan Cun Street, Beijing 100081, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 1 North 2nd Street, Zhong Guan Cun, Beijing 100190, China.
Biomater Sci. 2020 Apr 15;8(8):2283-2288. doi: 10.1039/d0bm00088d.
Highly efficient tumor-targeted therapy remains a great challenge due to the complexity and heterogeneity of tumor tissues. Herein, we developed an in vivo two-step tumor-targeting strategy by combining metabolic lipid-engineering with a stain-promoted azide-alkyne 1,3-dipolar cycloaddition (SPAAC) reaction, independent of the tumor microenvironment and cell phenotype. Firstly, exogenously-supplied azidoethyl-cholines (AECho) were metabolically incorporated into the cell membranes in tumor tissues through the intrinsic biosynthesis of phosphatidylcholine. The pre-inserted and accumulated azido groups (N3) could subsequently serve as 'artificial chemical receptors' for the specific anchoring of dibenzocyclooctyne (DBCO) modified biomimetic nanoparticles (DBCO-RBCG@ICG) via in situ click chemistry, resulting in significantly enhanced tumor-targeting and then an improved photothermal therapy effect. Such a two-step targeting strategy based on these cutting-edge techniques provided new insights into the universal and precise functionalization of living tissues for site-specific drug delivery in the diagnosis and treatment of various diseases.
由于肿瘤组织的复杂性和异质性，高效的肿瘤靶向治疗仍然是一个巨大的挑战。在此，我们通过将代谢脂质工程与促染叠氮-炔 1,3-偶极环加成（SPAAC）反应相结合，开发了一种体内两步肿瘤靶向策略，该策略不依赖于肿瘤微环境和细胞表型。首先，外源性的叠氮乙基胆碱（AECho）通过磷脂酰胆碱的内在生物合成被代谢掺入肿瘤组织的细胞膜中。随后，预先插入和积累的叠氮基团（N3）可作为“人工化学受体”，通过原位点击化学特异性锚定二苯并环辛炔（DBCO）修饰的仿生纳米颗粒（DBCO-RBCG@ICG），从而显著增强肿瘤靶向性，进而提高光热治疗效果。这种基于这些前沿技术的两步靶向策略为活组织的通用和精确功能化提供了新的见解，可用于各种疾病的诊断和治疗中的特定部位药物输送。
