Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, P.R. China.
Biomater Sci. 2020 Mar 17;8(6):1658-1668. doi: 10.1039/c9bm01843c.
An abnormal tumor growth induces solid stress in tumors, thus reducing blood perfusion. As a result, the impaired blood perfusion, with dense interstitial matrix in tumors significantly reduces the penetration and efficacy of nanotherapeutics. In this study, we have developed a losartan-loaded polydopamine nanoparticle (PLST) for the enhanced delivery of nanoparticles to tumors and improved photothermal cancer therapy. Losartan, an angiotensin inhibitor, is also able to alleviate the solid stress in tumors. It was laden on polydopamine nanoparticles via π-π stacking and was released upon tumor extracellular acidity. PLST reduced collagen production in vitro along with the lowered expression of profibrotic factors of TGF-β1, CCN2, and TIMP-1. The in vivo studies reveal that PLST reduced solid stress in tumors, and the amount of PLST accumulated in tumors was enhanced. The efficiency of the photothermal ablation of tumors was significantly enhanced by using PLST.
异常肿瘤生长会在肿瘤中引起固体应力,从而减少血液灌注。结果,受损的血液灌注加上肿瘤中密集的细胞间质基质,显著降低了纳米药物的穿透性和疗效。在这项研究中,我们开发了一种载有洛沙坦的聚多巴胺纳米颗粒(PLST),用于增强纳米颗粒向肿瘤的传递和改善光热癌症治疗。洛沙坦是一种血管紧张素抑制剂,也能够缓解肿瘤中的固体应力。它通过π-π堆积作用负载在聚多巴胺纳米颗粒上,并在肿瘤细胞外酸性条件下释放。PLST 减少了体外胶原蛋白的产生,同时降低了 TGF-β1、CCN2 和 TIMP-1 等促纤维化因子的表达。体内研究表明,PLST 降低了肿瘤中的固体应力,并且 PLST 在肿瘤中的积累量也增加了。使用 PLST 显著增强了肿瘤的光热消融效率。