Abstract

Drug delivery with the help of nanoparticles could transport more payloads to tumour site. Owing to their limited accumulation and penetration in the tumour tissues, to increase delivery efficiency is currently still required for applying nanomedicine to treat tumour. Here, we initially report a pressure-driven accumulation of drug-loaded nanoparticles to tumours for efficient tumour therapy with a dry cupping device. The mesoporous Mn-doped silica based nanoparticles delivering 5-aza-2-deoxycytidine and docetaxel were prepared, characterised and used as a model nanomedicine to investigate the potential of dry cupping treatment. For this system, the Mn doping not only endowed the mesoporous silica nanoparticles biodegradability, but also made it much easier to bind a tumour targeting group, which is a G-quadruplex-forming aptamer AS1411. On tumour-bearing mice, the in vivo results demonstrated that the dry cupping treatment could substantially improve the distribution of nanomedicines at tumour site, resulting in enhanced treatment efficacy. Overall, this method enables the therapeutical nanoparticles accumulate to tumour through increasing the blood perfusion as well as altering the biological barrier, which opened up possibilities for the development of pressure-driven nanomedicine accumulation at tumour site.

摘要

借助纳米粒子的药物递送可以将更多的有效载荷运送到肿瘤部位。由于它们在肿瘤组织中的有限积累和渗透，目前仍需要提高递送效率来应用纳米药物治疗肿瘤。在这里，我们最初报告了一种压力驱动的载药纳米颗粒在肿瘤上的积累，用于使用干式拔罐装置进行有效的肿瘤治疗。制备、表征了介孔 Mn 掺杂的二氧化硅基纳米粒子传递 5-aza-2-deoxycytidine 和多西紫杉醇，并将其用作模型纳米药物，以研究干拔罐治疗的潜力。对于该系统，Mn 的掺杂不仅赋予了介孔二氧化硅纳米粒子的生物降解性，而且还使其更容易结合肿瘤靶向基团，即形成 G-四链体的适体 AS1411。体内结果表明，干拔罐治疗可以显着改善纳米药物在肿瘤部位的分布，从而提高治疗效果。总体而言，该方法通过增加血液灌注和改变生物屏障使治疗性纳米颗粒聚集到肿瘤中，这为在肿瘤部位开发压力驱动的纳米药物积累开辟了可能性。