Zywot Emilia M, Orlova Natalia, Ding Song, Rampersad Rishi R, Rabjohns Emily M, Wickenheisser Victoria A, Wang Qunzhao, Welfare Joshua G, Haar Lauren, Eudy Amanda M, Tarrant Teresa K, Lawrence David S
Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Medicine, Division of Rheumatology and Immunology, Duke University, Durham, NC 27710, USA.
Adv Ther (Weinh). 2022 Jan;5(1). doi: 10.1002/adtp.202100159. Epub 2021 Oct 13.
Arthritis is a leading cause of disability in adults, which can be intensely incapacitating. The location and intensity of the pain is both subjective and challenging to manage. Consequently, patient-directed delivery of anti-inflammatories is an essential component of future therapeutic strategies for the management of this disorder. We describe the design and application of a light responsive red blood cell (RBC) conveyed dexamethasone (Dex) construct that enables targeted drug delivery upon illumination of the inflamed site. The red wavelength (650 nm) responsive nature of the phototherapeutic was validated using tissue phantoms mimicking the light absorbing properties of various skin types. Furthermore, photoreleased Dex has the same impact on cellular responses as conventional Dex. Murine RBCs containing the photoactivatable therapeutic display comparable circulation properties as fluorescently labelled RBCs. In addition, a single dose of light-targeted Dex delivery is 5-fold more effective in suppressing inflammation than the parent drug, delivered serially over multiple days. These results are consistent with the notion that the circulatory system be used as an on-command drug depot, providing the means to therapeutically target diseased sites both efficiently and effectively.
关节炎是成年人残疾的主要原因，会导致严重的行动不便。疼痛的部位和强度都具有主观性，且难以控制。因此，以患者为导向的抗炎药给药方式是未来治疗该疾病策略的重要组成部分。我们描述了一种光响应性红细胞（RBC）携带地塞米松（Dex）构建体的设计与应用，该构建体能够在炎症部位受光照时实现靶向药物递送。使用模拟各种皮肤类型光吸收特性的组织模型验证了光疗法对红色波长（650nm）的响应特性。此外，光释放的地塞米松对细胞反应的影响与传统地塞米松相同。含有可光激活治疗剂的小鼠红细胞与荧光标记的红细胞具有相似的循环特性。此外，单次光靶向地塞米松递送在抑制炎症方面比连续多天给药的母体药物有效5倍。这些结果与将循环系统用作按需药物库的观点一致，为有效治疗患病部位提供了手段。
