Efficient tumor-targeted drug delivery is still a challenging and currently unbreakable bottleneck in chemotherapy for tumors. Nanomedicines based on passive or active targeting strategy have not yet achieved convincing chemotherapeutic benefits in the clinic due to the tumor heterogeneity. Inspired by the efficient inflammatory-cell recruitment to acute clots, we constructed a two-component nanosystem, which is composed of an RGD-modified pyropheophorbide-a (Ppa) micelle (PPRM) that mediates the tumor vascular-targeted photodynamic reaction to activate local coagulation and subsequently transmits the coagulation signals to the circulating clot-targeted CREKA peptide-modified camptothecin (CPT)-loaded nanodiscs (CCNDs) for amplifying tumor targeting. PPRM could effectively bind with the tumor vasculature and induce sufficient local thrombus by a photodynamic reaction. Local photodynamic reaction-induced tumor target amplification greatly increased the tumor accumulation of CCND by 4.2 times, thus significantly enhancing the chemotherapeutic efficacy in the 4T1 breast tumor model. In other words, this study provides a powerful platform to amplify tumor-specific drug delivery by taking advantage of the efficient crosstalk between the PPRM-activated coagulation cascade and clot-targeted CCND.

中文翻译：

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光动力肿瘤血管破坏放大纳米颗粒肿瘤靶向以实现高效化疗


高效的肿瘤靶向药物递送仍然是肿瘤化疗中具有挑战性且难以突破的瓶颈。由于肿瘤的异质性，基于被动或主动靶向策略的纳米药物尚未在临床上取得令人信服的化疗效果。受炎症细胞有效募集到急性血栓的启发，我们构建了一种双组分纳米系统，该系统由 RGD 修饰的焦脱镁叶绿酸-a (Ppa) 胶束 (PPRM) 组成，可介导肿瘤血管靶向光动力反应以激活局部凝血，随后将凝血信号传输至循环凝块靶向的 CREKA 肽修饰喜树碱 (CPT) 负载纳米圆盘 (CCND)，以放大肿瘤靶向。 PPRM可以有效地与肿瘤脉管系统结合，并通过光动力反应诱导足够的局部血栓。局部光动力反应诱导的肿瘤靶点放大使CCND的肿瘤积累大大增加了4.2倍，从而显着增强了4T1乳腺肿瘤模型的化疗效果。换句话说，这项研究提供了一个强大的平台，通过利用 PPRM 激活的凝血级联和凝块靶向 CCND 之间的有效串扰来放大肿瘤特异性药物输送。