Li Zhiliang, Li Shukun, Guo Yanhui, Yuan Chengqian, Yan Xuehai, Schanze Kirk S
Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, United States.
Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao, Shandong 266237, China.
ACS Nano. 2021 Mar 23;15(3):4979-4988. doi: 10.1021/acsnano.0c09913. Epub 2021 Mar 12.
Engineering photosensitizers into stimuli-responsive supramolecular nanodrugs allows enhanced spatiotemporal delivery and controllable release of photosensitizers, which is promising for dedicated and precise tumor photodynamic therapy. Complicated fabrication for nanodrugs with good tumor accumulation capability and the undesirable side-effects caused by the drug components retards the application of PDT . The fact that extracellular adenosine triphosphate (ATP) is overexpressed in tumor tissue has been overlooked in fabricating nanomedicines for tumor-targeting delivery. Hence, herein we present metal-free helical nanofibers formed in aqueous solution from the coassembly of a cationic porphyrin and ATP as a nanodrug for PDT. The easily accessible and compatible materials and simple preparation enable the nanodrugs with potential in PDT for cancer. Compared to the cationic porphyrin alone, the porphyrin-ATP nanofibers exhibited enhanced tumor-site photosensitizer delivery through whole-body blood circulation. Overexpressed extracellular ATP stabilizes the porphyrin-ATP nanodrug within tumor tissue, giving rise to enhanced uptake of the nanodrug by cancer cells. The enzyme-triggered release of photosensitizers from the nanodrugs upon biodegradation of ATP by intracellular phosphatases results in good tumor therapeutic efficacy. This study demonstrates the potential for employing the tumor microenvironment to aid the accumulation of nanodrugs in tumors, inspiring the fabrication of smart nanomedicines.
将光敏剂设计成刺激响应性超分子纳米药物可实现光敏剂增强的时空递送和可控释放，这对于专门且精确的肿瘤光动力疗法很有前景。具有良好肿瘤蓄积能力的纳米药物的复杂制备以及药物成分引起的不良副作用阻碍了光动力疗法的应用。细胞外三磷酸腺苷（ATP）在肿瘤组织中过表达这一事实在制备用于肿瘤靶向递送的纳米药物时被忽视了。因此，在此我们展示了由阳离子卟啉和ATP在水溶液中共同组装形成的无金属螺旋纳米纤维作为用于光动力疗法的纳米药物。易于获取且兼容的材料以及简单的制备方法使这种纳米药物在癌症光动力疗法中具有潜力。与单独的阳离子卟啉相比，卟啉 - ATP纳米纤维通过全身血液循环表现出增强的肿瘤部位光敏剂递送。过表达的细胞外ATP使卟啉 - ATP纳米药物在肿瘤组织内稳定，从而导致癌细胞对纳米药物的摄取增加。细胞内磷酸酶对ATP进行生物降解后，纳米药物中光敏剂的酶触发释放导致良好的肿瘤治疗效果。这项研究证明了利用肿瘤微环境来帮助纳米药物在肿瘤中蓄积的潜力，激发了智能纳米药物的制备。
