Covalent organic framework (COF) nanoparticles for interference-free targeted drug delivery to glioma remains in its infancy. Herein, hollow COF nanospheres with high crystallinity and uniformed sizes were facilely prepared via heterogeneous nucleation-growth. The prepared COF had large surface area/pore volume and exhibited appropriate degradation behavior under acid environment, where therefore doxorubicin was effectively encapsulated and exhibited a pH-sensitive release. Most charmingly, T₁₀ peptide that has high affinity with transferrin (Tf), was conjugated to endow the hollow COF interesting properties to specifically absorb Tf in vivo as Tf corona. For the first time, multifunctional hollow COF nanospheres (the better one named DCPT-2) were successfully synthesized to achieve interference-free cascade-targeting glioma drug delivery across the blood-brain barrier. Treatment with DCPT-2 brought an improved therapeutic outcome with significantly prolonged median survival time and low side effects. This work promised not only a potential protein corona-mediated COF-based drug delivery platform with good biocompatibility for effective and precise brain tumor therapy, but also an endogenous protein corona-mediated targeting strategy for general cancer therapy.

用于将药物无干扰地靶向递送至神经胶质瘤的共价有机骨架（COF）纳米粒子仍处于婴儿期。在此，通过异质形核-生长容易地制备了具有高结晶度和均一尺寸的中空COF纳米球。所制备的COF具有大的表面积/孔体积，并且在酸性环境下表现出适当的降解行为，因此阿霉素被有效地包封并且表现出pH敏感的释放。最迷人的是，与运铁蛋白（Tf）具有高亲和力的T ₁₀肽被缀合以赋予空心COF有趣的特性，以在体内特异性吸收Tf作为Tf电晕。首次成功地合成了多功能空心COF纳米球（更好的命名为DCPT-2），以实现跨血脑屏障的无干扰级联靶向神经胶质瘤药物递送。DCPT-2的治疗带来了改善的治疗结果，中位生存时间显着延长，副作用低。这项工作不仅为潜在的基于蛋白电晕介导的基于COF的药物递送平台提供了有效而精确的脑肿瘤治疗的良好生物相容性，而且为一般癌症治疗提供了一种内源性蛋白电晕介导的靶向策略。