光动力治疗是一种新颖的已成功转化于临床应用的光触发肿瘤治疗手段，近些年来，肿瘤血管靶向光动力治疗策略受到重点关注。然而，已有的血管靶向光动力治疗方法存在诱发和加重肿瘤组织缺氧应激、肿瘤边缘区域的血管不敏感导致肿瘤复发等瓶颈。本项目在前期工作基础上，率先构建集双靶向光动力治疗和缺氧活化的前药化疗于一体的多模式治疗纳米药物 — cRGDfK多肽修饰的共装载光敏剂维替泊芬（VP）和缺氧活化的前药AQ4N的氧化石墨烯（GO）隐形纳米粒（cRGDfK-pGO-VP-AQ4N）。该纳米药物具有程序性、多功能抗肿瘤特性：通过靶向光动力治疗直接杀伤肿瘤血管内皮细胞和肿瘤细胞，通过抗血管作用诱导肿瘤组织缺氧、坏死，继发AQ4N在缺氧环境中活化杀伤残存的缺氧应激下的肿瘤细胞，实现肿瘤靶向光动力治疗和缺氧活化的前药化疗的有机结合。这一多模式肿瘤靶向治疗策略和相关研究国内外未见报道，具有很高的创新价值。

Photodynamic therapy is a novel light-triggered therapeutic strategy that has been successfully translated into cancer clinic. In recent years, vascular-targeted photodynamic therapy (VTP) has been given more and more attention due to the central role of tumor angiogenesis in cancer development and the R&D breakthrough of antiangiogenic drugs. However, the previously reported VTP methods have encountered two bottlenecks shown in the triggering/aggravating tumor hypoxia stress and low sensitive, resistant peripheral tumor vasculature, both of which finally lead to comprised therapeutic efficacy and tumor relapse. In this proposal, a new nanomedicine, cRGDfK peptide-modified stealth graphene oxide (GO) nanoparticles co-deliverying photosensitizer verteporfin (VP) and hypoxia-activated prodrug AQ4N (cRGDfK-pGO-VP-AQ4N), is smartly engineered. This nanomedicine can exert programmed multi-modality anticancer functions of directly killing tumor vascular endothelial cells and tumor cells by the dual-targeting photodynamic therapy, inducing tumor hypoxia and necrosis through the VTP-mediated antivascular effects, and killing the remaining hypoxia-stressed tumor cells by AQ4 (a potent inhibitor of Topoisomerase Ⅱ) transformed from AQ4N under hypoxia. Our innovative investigation will provide new theoretical ideas and guidance in the development of tumor-targeted photodynamic therapy, chemotherapy with hypoxia-activated pro-drug, and their clinical translation.