Li Anshuo, Zhang Tiantian, Zhang Xuwu, Xu Zichuang, Liu Hengrui, Yuan Meng, Wei Xindi, Zhu Yuhui, Tu Wenkang, Jiang Xinquan, He Yuchu
State Key Laboratory of Metastable Materials Science and Technology, Nano-biotechnology Key Lab of Hebei Province, Applying Chemistry Key Lab of Hebei Province, Heavy Metal Deep-Remediation in Water and Resource Reuse Key Lab of Hebei, Yanshan University, Qinhuangdao 066004, China.
Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai 200011, China.
ACS Nano. 2024 Feb 8. doi: 10.1021/acsnano.3c09316.
The practical efficacy of nanomedicines for treating solid tumors is frequently low, predominantly due to the elevated interstitial pressure within such tumors that obstructs the penetration of nanomedicines. This increased interstitial pressure originates from both liquid and solid stresses related to an undeveloped vascular network and excessive fibroblast proliferation. To specifically resolve the penetration issues of nanomedicines for tumor treatment, this study introduces a holistic "dual-faceted" approach. A treatment platform predicated on the WS/Pt Schottky heterojunction was adopted, and flexocatalysis technology was used to disintegrate tumor interstitial fluids, thus producing oxygen and reactive oxygen species and effectively mitigating the interstitial fluid pressure. The chemotherapeutic agent curcumin was incorporated to further suppress the activity of cancer-associated fibroblasts, minimize collagen deposition in the extracellular matrix, and alleviate solid stress. Nanomedicines achieve homologous targeting by enveloping the tumor cell membrane. It was found that this multidimensional strategy not only alleviated the high-pressure milieu of the tumor interstitium─which enhanced the efficiency of nanomedicine delivery─but also triggered tumor cell apoptosis via the generated reactive oxygen species and modulated the tumor microenvironment. This, in turn, amplified immune responses, substantially optimizing the therapeutic impacts of nanomedicines.
纳米药物治疗实体瘤的实际疗效通常较低，主要原因是此类肿瘤内的间质压力升高，阻碍了纳米药物的渗透。这种间质压力增加源于与未发育完善的血管网络和过度的成纤维细胞增殖相关的液体和固体应力。为了具体解决纳米药物用于肿瘤治疗的渗透问题，本研究引入了一种整体的“双方面”方法。采用了基于WS/Pt肖特基异质结的治疗平台，并利用柔性催化技术分解肿瘤间质液，从而产生氧气和活性氧，有效减轻间质液压力。加入化疗药物姜黄素以进一步抑制癌症相关成纤维细胞的活性，减少细胞外基质中的胶原蛋白沉积，并减轻固体应力。纳米药物通过包裹肿瘤细胞膜实现同源靶向。研究发现，这种多维策略不仅缓解了肿瘤间质的高压环境——提高了纳米药物递送的效率——还通过产生的活性氧触发肿瘤细胞凋亡，并调节肿瘤微环境。这反过来又放大了免疫反应，大幅优化了纳米药物的治疗效果。
