瞬态流体流动可改善光免疫偶联物递送及光免疫治疗效果。

Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy.

作者信息

Sorrin Aaron J, Zhou Keri, May Katherine, Liu Cindy, McNaughton Kathryn, Rahman Idrisa, Liang Barry J, Rizvi Imran, Roque Dana M, Huang Huang-Chiao

机构信息

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.

Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, North Carolina State University, Raleigh, NC 27599, USA.

出版信息

iScience. 2023 Jun 26;26(8):107221. doi: 10.1016/j.isci.2023.107221. eCollection 2023 Aug 18.

DOI:10.1016/j.isci.2023.107221

PMID:37520715

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10372742/

Abstract

Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian cancer treatment. Photoimmunotherapy, an emerging modality with potential for the treatment of ovarian cancer, involves near-infrared light activation of antibody-photosensitizer conjugates (photoimmunoconjugates) to generate cytotoxic reactive oxygen species. Here, a microfluidic cell culture model is used to study how fluid flow-induced shear stress affects photoimmunoconjugate delivery to ovarian cancer cells. Photoimmunoconjugates are composed of the antibody, cetuximab, conjugated to the photosensitizer, and benzoporphyrin derivative. Longitudinal tracking of photoimmunoconjugate treatment under flow conditions reveals enhancements in subcellular photosensitizer accumulation. Compared to static conditions, fluid flow-induced shear stress at 0.5 and 1 dyn/cm doubled the cellular delivery of photoimmunoconjugates. Fluid flow-mediated treatment with three different photosensitizer formulations (benzoporphyrin derivative, photoimmunoconjugates, and photoimmunoconjugate-coated liposomes) led to enhanced phototoxicity compared to static conditions. This study confirms the fundamental role of fluid flow-induced shear stress in the anti-cancer effects of photoimmunotherapy.

摘要

在腹腔中循环给药是晚期卵巢癌治疗的一种有效策略。光免疫疗法是一种新兴的卵巢癌治疗方式，它涉及通过近红外光激活抗体 - 光敏剂偶联物（光免疫偶联物）来产生活性细胞毒性氧物质。在此，我们使用一种微流控细胞培养模型来研究流体流动诱导的剪切应力如何影响光免疫偶联物向卵巢癌细胞的递送。光免疫偶联物由与光敏剂苯并卟啉衍生物偶联的抗体西妥昔单抗组成。在流动条件下对光免疫偶联物治疗进行纵向追踪，结果显示亚细胞光敏剂积累增加。与静态条件相比，0.5和1达因/平方厘米的流体流动诱导剪切应力使光免疫偶联物的细胞递送量增加了一倍。与静态条件相比，用三种不同的光敏剂制剂（苯并卟啉衍生物、光免疫偶联物和光免疫偶联物包被的脂质体）进行流体流动介导的治疗导致光毒性增强。这项研究证实了流体流动诱导的剪切应力在光免疫疗法抗癌作用中的重要作用。