B cell-targeted polylactic acid nanoparticles as platform for encapsulating jakinibs: potential therapeutic strategy for systemic lupus erythematosus

• Published in: Nanomedicine (London, England) England), 2023-11, Vol.18 (27), p.2001-2019
• Main Authors: Álvarez, Karen, Palacio, Juliana, Agudelo, Natalia A, Anacona, Cristian A, Castaño, Diana, Vásquez, Gloria, Rojas, Mauricio
• Format: Article
• Language: English
• Subjects: B cells; JAK-STAT pathway; lupus; nanoparticles; polylactic acid
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm-2023-0241

B cells are pivotal in systemic lupus erythematosus and autoimmune disease pathogenesis. To address this, Nile Red-labeled polylactic acid nanoparticles (NR-PLA NPs) loaded with the JAK inhibitor baricitinib (BARI), specifically targeting JAK1 and JAK2 in B cells, were developed. Physicochemical characterization confirmed NP stability over 30 days. NR-PLA NPs were selectively bound and internalized by CD19 B cells, sparing other leukocytes. In contrast to NR-PLA NPs, BARI-NR-PLA NPs significantly dampened B-cell activation, proliferation and plasma cell differentiation in healthy controls. They also inhibited key cytokine production. These effects often surpassed those of equimolar-free BARI. This study underscores the potential of PLA NPs to regulate autoreactive B cells, offering a novel therapeutic avenue for autoimmune diseases. In this study, a new approach to treating autoimmune diseases, particularly systemic lupus erythematosus, was investigated by focusing on a type of immune cell called B cells. Special nanoparticles (NPs) labeled with Nile Red (NR) and made from polylactic acid (PLA) were created. These NPs were loaded with a drug called baricitinib (BARI), which targets specific proteins (JAK1 and JAK2) in B cells. This was done to determine if these NPs could help control the behavior of B cells, which are important in autoimmune diseases. First, these NPs remained stable for a long time (30 days). The NR-labeled PLA NPs (NR-PLA NPs) were also good at attaching to and entering a specific type of B cell called CD19 B cells while leaving other types of immune cells alone. The use of NR-PLA NPs loaded with BARI produced exciting results. These NPs were better at reducing the activity, growth and transformation of B cells into plasma cells compared with the drug BARI by itself. They also stopped the production of certain immune system signals called cytokines, which are usually overactive in autoimmune diseases. This work suggests that PLA NPs could be a promising way to control overactive B cells that contribute to autoimmune diseases like systemic lupus erythematosus. This could open a new and exciting path for developing treatments for these conditions.