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Vascular Bursts Act as a Versatile Tumor Vessel Permeation Route for Blood-Borne Particles and Cells
Small ( IF 13.0 ) Pub Date : 2021-09-15 , DOI: 10.1002/smll.202103751 Kazunori Igarashi 1, 2 , Horacio Cabral 2 , Taehun Hong 2 , Yasutaka Anraku 2 , Fotios Mpekris 3 , Triantafyllos Stylianopoulos 3 , Thahomina Khan 4 , Akira Matsumoto 4, 5 , Kazunori Kataoka 6, 7 , Yu Matsumoto 1 , Tatsuya Yamasoba 1
Small ( IF 13.0 ) Pub Date : 2021-09-15 , DOI: 10.1002/smll.202103751 Kazunori Igarashi 1, 2 , Horacio Cabral 2 , Taehun Hong 2 , Yasutaka Anraku 2 , Fotios Mpekris 3 , Triantafyllos Stylianopoulos 3 , Thahomina Khan 4 , Akira Matsumoto 4, 5 , Kazunori Kataoka 6, 7 , Yu Matsumoto 1 , Tatsuya Yamasoba 1
Affiliation
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Dynamic bursting in tumor vasculature has recently sparked interest as a novel particle transportation route for drug delivery. These bursts facilitate the transport of sub-100 nm nanoparticles into tumors, though their contribution on the access of other blood-borne particles remains unknown. To evaluate the versatility of this phenomenon, the in vivo kinetics of a variety of intravenously injected particles and their penetration in tumor xenografts and allografts are compared. Dextran, polymeric micelles, liposomes, and polymeric vesicles with diameters ranging from 32 to 302 nm are found to colocalize in virtually all vascular bursts. By mathematical modeling, the burst vent size is estimated to be 625 nm or larger, indicating the dynamic and stochastic formation of large permeation routes in tumor vasculature. Furthermore, some burst vents are found to be µm-sized, allowing the transport of 1 µm microspheres. Moreover, antibody drugs and platelets are capable of utilizing vascular burst transportation, demonstrating the application of this phenomenon to other types of therapeutics and cellular components. These findings indicate the vast potential of vascular bursts, extending the biological and therapeutic significance of this phenomenon to a wide range of blood-borne particles and cells.
中文翻译：
血管爆裂作为血源性颗粒和细胞的多功能肿瘤血管渗透途径
肿瘤脉管系统中的动态爆发最近引起了人们的兴趣，作为一种新型的药物输送颗粒运输途径。这些爆发促进了亚 100 nm 纳米粒子进入肿瘤的传输，尽管它们对其他血源性粒子进入的贡献仍然未知。为了评估这种现象的多功能性，比较了各种静脉注射颗粒的体内动力学及其在肿瘤异种移植物和同种异体移植物中的渗透。发现葡聚糖、聚合物胶束、脂质体和直径范围为 32 到 302 nm 的聚合物囊泡在几乎所有血管爆发中都存在。通过数学建模，爆裂孔尺寸估计为 625 nm 或更大，表明肿瘤脉管系统中大渗透途径的动态和随机形成。此外，发现一些爆裂孔是微米级的，允许运输 1 微米的微球。此外，抗体药物和血小板能够利用血管爆发运输，证明了这种现象在其他类型的治疗方法和细胞成分中的应用。这些发现表明血管爆裂的巨大潜力，将这种现象的生物学和治疗意义扩展到广泛的血源性颗粒和细胞。
更新日期：2021-10-21
中文翻译：
血管爆裂作为血源性颗粒和细胞的多功能肿瘤血管渗透途径
肿瘤脉管系统中的动态爆发最近引起了人们的兴趣，作为一种新型的药物输送颗粒运输途径。这些爆发促进了亚 100 nm 纳米粒子进入肿瘤的传输，尽管它们对其他血源性粒子进入的贡献仍然未知。为了评估这种现象的多功能性，比较了各种静脉注射颗粒的体内动力学及其在肿瘤异种移植物和同种异体移植物中的渗透。发现葡聚糖、聚合物胶束、脂质体和直径范围为 32 到 302 nm 的聚合物囊泡在几乎所有血管爆发中都存在。通过数学建模，爆裂孔尺寸估计为 625 nm 或更大，表明肿瘤脉管系统中大渗透途径的动态和随机形成。此外，发现一些爆裂孔是微米级的，允许运输 1 微米的微球。此外，抗体药物和血小板能够利用血管爆发运输，证明了这种现象在其他类型的治疗方法和细胞成分中的应用。这些发现表明血管爆裂的巨大潜力，将这种现象的生物学和治疗意义扩展到广泛的血源性颗粒和细胞。
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