Abstract：
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.
摘要：
有效的EPR和肿瘤渗透是当前纳米医学治疗的瓶颈。利用Comosol软件分析了不同形状的纳米粒子(NPs)的运动过程,从血管到肿瘤组织，来解决这个问题。通过计算,海胆状NP比球形NP承受更高的阻力，促进它们的EPR和肿瘤渗透效应。因此，通过利用ICG响应近红外光（NIR）的不稳定性，制备了类海胆的吲哚菁绿色负载的羟乙基淀粉胆固醇（ICG@HES-CH）NP。在NIR暴露后，ICG降解并部分分解ICG@HES-CHNPs，形态从球形转变为海胆状。长春新碱（VC），作为一种模范药物，装载在海胆样ICG@HES-CHNP中用于治疗淋巴瘤。A20淋巴瘤细胞和3T3-A20肿瘤类器官用于研究形状对NPs细胞摄取的影响，渗透途径,和细胞毒性。这表明海胆样ICG@HES-CHNPs主要通过细胞间途径转运穿过细胞外基质，容易到达深部肿瘤部位并获得较高的细胞毒性。体内VC分布和抗肿瘤结果表明，海胆样NPs增加了VC的EPR和穿透能力，降低VC的神经毒性和优越的抗肿瘤后果。因此,海胆样ICG@HES-CHNPs具有巨大的翻译潜力，可用作抗癌治疗中的化疗纳米载体。
