Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R. China.
Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China.
ACS Nano. 2023 Sep 12;17(17):17285-17298. doi: 10.1021/acsnano.3c05232. Epub 2023 Aug 18.
Tumor interstitial pressure represents the greatest barrier against drug diffusion into the depth of the tumor. Biometric nanomotors highlight the possibility of enhanced deep penetration and improve cellular uptake. However, control of their directionality remains difficult to achieve. Herein, we report cysteine-arginine-glutamic acid-lysine-alanine (CREKA)-modified ceria@polydopamine nanobowls as tumor microenvironment-fueled nanoscale motors for positive chemotaxis into the tumor depth or toward tumor cells. Upon laser irradiation, this nanoswimmer rapidly depletes the tumor microenvironment-specific hydrogen peroxide (HO) in the nanobowl, contributing to a self-generated gradient and subsequently propulsion (9.5 μm/s at 46 °C). Moreover, the asymmetrical modification of CREKA on nanobowls could automatically reconfigure the motion direction toward tumor depth or tumor cells in response to receptor-ligand interaction, leading to a deep penetration (70 μm in multicellular spheroids) and enhanced antitumor effects over conventional nanomedicine-induced chemo-photothermal therapy (tumor growth inhibition rate: 84.2% versus 56.9%). Thus, controlling the direction of nanomotors holds considerable potential for improved antitumor responses, especially in solid tumors with high tumor interstitial pressure.
肿瘤间质压力是药物扩散到肿瘤深处的最大障碍。生物计量纳米马达突出了增强深层渗透和提高细胞摄取的可能性。然而，控制其方向性仍然难以实现。在此，我们报告了半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸（CREKA）修饰的氧化铈@聚多巴胺纳米碗作为肿瘤微环境驱动的纳米级马达，用于向肿瘤深处或肿瘤细胞进行正趋化运动。激光照射后，这种纳米游泳者迅速耗尽纳米碗中肿瘤微环境特异性的过氧化氢（HO），有助于自生成梯度，从而推动其前进（在 46°C 时为 9.5 μm/s）。此外，CREKA 在纳米碗上的不对称修饰可以自动响应受体-配体相互作用重新配置运动方向朝向肿瘤深处或肿瘤细胞，从而实现深层渗透（在多细胞球体中为 70 μm），并提高传统纳米医学诱导的化学-光热治疗的抗肿瘤效果（肿瘤生长抑制率：84.2% 对 56.9%）。因此，控制纳米马达的方向对于改善抗肿瘤反应具有相当大的潜力，特别是在间质压力较高的实体瘤中。
