Simões Marina M, Paiva Karen L R, de Souza Isadora Florêncio, Mello Victor Carlos, Martins da Silva Ingrid Gracielle, Souza Paulo Eduardo Narcizo, Muehlmann Luis Alexandre, Báo Sônia Nair
Laboratory of Microscopy and Microanalysis, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasilia 70910-900, DF, Brazil.
Optical Spectroscopy Laboratory, Institute of Physics, University of Brasilia, Brasilia 70910-900, DF, Brazil.
Pharmaceutics. 2024 Jul 14;16(7):941. doi: 10.3390/pharmaceutics16070941.
Photodynamic therapy (PDT) uses a photosensitizer to generate reactive oxygen species (ROS) that kill target cells. In cancer treatments, PDT can potentially induce immunogenic cell death (ICD), which is characterized by a well-controlled exposure of damage-associated molecular patterns (DAMPs) that activate dendritic cells (DCs) and consequently modulate the immune response in the tumor microenvironment. However, PDT still has limitations, such as the activity of photosensitizers in aqueous media and poor bioavailability. Therefore, a new photosensitizer system, SLN-AlPc, has been developed to improve the therapeutic efficacy of PDT. In vitro experiments showed that the light-excited nanocarrier increased ROS production in murine melanoma B16-F10 cells and modulated the profile of DCs. PDT induced cell death accompanied by the exposure of DAMPs and the formation of autophagosomes. In addition, the DCs exposed to PDT-treated B16-F10 cells exhibited morphological changes, increased expression of MHCII, CD86, CD80, and production of IL-12 and IFN-γ, suggesting immune activation towards an antitumor profile. These results indicate that the SLNs-AlPc protocol has the potential to improve PDT efficacy by inducing ICD and activating DCs.
光动力疗法(PDT)利用一种光敏剂来产生活性氧(ROS),从而杀死靶细胞。在癌症治疗中,PDT有可能诱导免疫原性细胞死亡(ICD),其特征在于损伤相关分子模式(DAMPs)的适度暴露,这些模式可激活树突状细胞(DCs),进而调节肿瘤微环境中的免疫反应。然而,PDT仍然存在局限性,例如光敏剂在水性介质中的活性以及较差的生物利用度。因此,已开发出一种新的光敏剂系统SLN - AlPc,以提高PDT的治疗效果。体外实验表明,光激发的纳米载体增加了小鼠黑色素瘤B16 - F10细胞中ROS的产生,并调节了DCs的特征。PDT诱导细胞死亡,同时伴有DAMPs的暴露和自噬体的形成。此外,暴露于经PDT处理的B16 - F10细胞的DCs表现出形态变化、MHCII、CD86、CD80表达增加以及IL - 12和IFN -γ的产生,表明朝着抗肿瘤特征的免疫激活。这些结果表明,SLNs - AlPc方案有可能通过诱导ICD和激活DCs来提高PDT疗效。