Laboratory for NanoMedical Photonics, School of Basic Medical Science, Henan University, Kaifeng, 475004, China.
Joint National Laboratory for Antibody Drug Engineering, School of Basic Medical Science, Henan University, Kaifeng, 475004, China.
Angew Chem Int Ed Engl. 2021 Jul 12;60(29):16215-16223. doi: 10.1002/anie.202105607. Epub 2021 Jun 14.
The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H O and OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
由于器官特异性药物的固有缺乏，癌症患者的药物系统治疗是在理想治疗和副作用之间的妥协。因此，设计和构建药物以实现器官特异性递送是非常需要的。我们在此调节并苯骨架以实现器官特异性，并在基于扭曲 PDIC-NC 的基础上展示了肺特异性分布的实例。我们进一步证明 PDIC-NC 可以靶向线粒体作为细胞呼吸抑制剂，导致三磷酸腺苷产生不足，促进内源性 H2O2 和·OH 爆发，钙超载升高，有效地触发肺癌细胞的协同凋亡、自噬和内质网应激。PDIC-NC 的抗肿瘤性能在体内异种移植、转移和原位肺癌中得到了验证，为潜在的临床应用提供了压倒性的证据。本研究为扭曲并苯实现肺特异性分布提供了概念验证，并同时实现了强烈的肺癌化疗。
