细小病毒 B19 样颗粒在实体瘤自发光光动力疗法中的应用。
Use of parvovirus B19-like particles in self-illuminated photodynamic therapy for solid tumors.
发表日期:2024 Jul 11
作者:
Ángel de Jesús Jiménez-Chávez, Leticia Moreno-Fierros, Maribel Cayetano-Cruz, Laura Patricia Romero-Romero, Ismael Bustos-Jaimes
来源:
J Photoch Photobio B
摘要:
生物发光共振能量转移光动力疗法利用生物发光蛋白产生的光来激活光敏剂并产生活性氧,无需外部照射,已在癌症模型中显示出有希望的结果。然而,仍然有必要对能够结合该疗法的成分以优先递送至肿瘤的递送系统进行表征。在这项工作中,我们将细小病毒 B19 样颗粒 (B19V-VLP) 表征为光敏剂和生物发光蛋白的平台。通过化学和双正交缀合,我们将孟加拉玫瑰光敏剂和萤火虫荧光素酶与 B19V-VLP 和蛋白质缀合以增加特异性。结果表明,B19V-VLP 可以承受所有三种成分的装饰,而不影响其结构或稳定性。结合的荧光素酶显示出活性,并且能够激活玫瑰红以产生单线态氧,而无需外部光。功能化的VLPs-B19产生的光动力反应可以降低体外肿瘤细胞的活力,并影响4T1模型中的肿瘤生长和转移。与载体治疗的小鼠相比,功能化 VLP-B19 治疗还增加了脾脏和腹股沟淋巴结中 CD4 和 CD8 细胞群的百分比。我们的结果支持 B19V-VLP 作为实体瘤生物发光光动力治疗成分的递送平台。版权所有 © 2023。由 Elsevier B.V 出版。
Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.Copyright © 2023. Published by Elsevier B.V.