有效的 EPR 和肿瘤渗透是当前纳米医学治疗的瓶颈。利用 Comosol 软件分析从血管到肿瘤组织等不同形状的纳米颗粒 (NP) 的运动过程，以解决这一问题。通过计算，海胆状纳米颗粒比球形纳米颗粒经历了更高的阻力，有利于其 EPR 和肿瘤穿透作用。因此，利用 ICG 对近红外光 (NIR) 响应的不稳定性，制备了类海胆吲哚菁绿负载羟乙基淀粉胆固醇 (ICG@HES-CH) 纳米颗粒。在近红外照射下，ICG 降解并部分分解了 ICG@HES-CH NP，其形态从球形转变为海胆状。将长春新碱（VC）作为模型药物负载在海胆样ICG@HES-CH NPs中用于治疗淋巴瘤。采用 A20 淋巴瘤细胞和 3T3-A20 肿瘤类器官研究形状对 NP 细胞摄取、渗透途径和细胞毒性的影响。表明海胆样ICG@HES-CH NPs主要通过细胞间途径跨细胞外基质运输，很容易到达肿瘤深处，并实现较高的细胞毒性。体内VC分布和抗肿瘤结果表明，海胆样纳米粒子增加了VC的EPR和渗透能力，降低了VC的神经毒性，具有优异的抗肿瘤作用。因此，类海胆 ICG@HES-CH NPs 具有巨大的转化潜力，可用作抗癌治疗中的化疗纳米载体。版权所有 © 2024。由 Elsevier B.V. 出版。

Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy.Copyright © 2024. Published by Elsevier B.V.