Lee Hyori, Park Byullee, Lee Jihye, Kang Yeoul, Han Moongyu, Lee Junseok, Kim Chulhong, Kim Won Jong
Department of Chemistry, POSTECH-CATHOLIC Biomedical Engineering Institute, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
Department of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, Medical Science and Engineering, and School of, Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
Small. 2023 Dec;19(50):e2303668. doi: 10.1002/smll.202303668. Epub 2023 Aug 23.
Transcytosis is an active transcellular transportation pathway that has garnered interest for overcoming the limited deep penetration of nanomedicines in solid tumors. In this study, a charge-convertible nanomedicine that facilitates deep penetration into solid tumors via transcytosis is designed. It is an albumin-based calcium phosphate nanomedicine loaded with IR820 (mAlb-820@CaP) for high-resolution photoacoustic imaging and enhanced photothermal therapy. Biomineralization on the surface stabilizes the albumin-IR820 complex during circulation and provides calcium ions (Ca ) for tissue penetration on degradation in an acidic environment. pH-triggered transcytosis of the nanomedicine enabled by caveolae-mediated endocytosis and calcium ion-induced exocytosis in 2D cellular, 3D spheroid, and in vivo tumor models is demonstrated. Notably, the extravasation and penetration ability of the nanomedicine is observed in vivo using a high-resolution photoacoustic system, and nanomedicine shows the most potent photothermal antitumor effect in vivo. Overall, the strategy provides a versatile theragnosis platform for both noninvasive photoacoustic imaging and high therapeutic efficiency resulting from deep penetration of nanomedicine.
转胞吞作用是一种活跃的跨细胞运输途径，因其能够克服纳米药物在实体瘤中深部渗透受限的问题而备受关注。在本研究中，设计了一种通过转胞吞作用促进深入实体瘤的电荷可转换纳米药物。它是一种负载IR820的基于白蛋白的磷酸钙纳米药物（mAlb-820@CaP），用于高分辨率光声成像和增强光热治疗。表面的生物矿化作用在循环过程中稳定白蛋白-IR820复合物，并在酸性环境中降解时为组织渗透提供钙离子（Ca）。在二维细胞、三维球体和体内肿瘤模型中，通过小窝介导的内吞作用和钙离子诱导的胞吐作用实现了纳米药物的pH触发转胞吞作用。值得注意的是，使用高分辨率光声系统在体内观察到了纳米药物的渗出和渗透能力，并且纳米药物在体内显示出最有效的光热抗肿瘤作用。总体而言，该策略为无创光声成像和纳米药物深度渗透带来的高治疗效率提供了一个多功能的诊疗平台。
