Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Article Title: Improved Efficacy of Triple-Negative Breast Cancer Immunotherapy via Hydrogel-Based Co-Delivery of CAR-T Cells and Mitophagy Agonist.
doi: 10.1002/advs.202409835
Figure Lengend Snippet: Figure 5. Engineering hydrogel therapeutic systems for cell delivery. A) Schematic diagram of the construction of the injectable hydrogel delivery system. This involves mixing a hydrogel mixture with a photoinitiator, CAR-T cells, and a mitophagy agonist (BC1618). The delivery system is then injected into the tumor site and subsequent photocuring with violet light at 405 nm is performed, resulting in the formation of a solidified hydrogel matrix embedded with CAR-T cells that are continuously released into the tumor microenvironment over time. B) Visualization of the growth kinetics of CAR-T-GFP cells within the hydrogel over a 48-hour period, as captured through 3D fluorescence imaging. A total of 1 × 105 CAR-T-GFP cells were encapsulated in the hydrogel, and CAR-T-GFP cell proliferation was measured via 3D fluorescence imaging at 0 h and 48 h. C) Quantification of the proliferation of CAR-T cells within the hydrogel compared with that in the culture medium over a 10-day period. The number of proliferating CAR-T cells cultured in the medium and hydrogel was counted every 10 days, (n = 3). D) The viability of CAR-T cells cultured in either medium or hydrogel over a 10-day period was measured via trypan blue staining, (n = 3). E) The levels of IL-2 and INF-𝛾in CAR-T cells from medium or hydrogel cocultured with MDA-MB-468 cell supernatant (n = 3). F) The number of released CAR-T cells in vitro was counted, (n = 3). G–H) The fluorescent dye for the hydrogel was added to detect the degradation of the hydrogel in vivo for 9 days (H), and the total ROI was measured (G). Representative images of the subcutaneous hydrogel on Days 0 and 9. (C, D, E) The data are shown as the means ± SDs and were analyzed via an unpaired t test. ns: p > 0.05.
Article Snippet: The most efficacious machine learning algorithms were subsequently curated for refinement and training of a classification model. A mitophagy library consisting of 45 mitophagy agonist compounds was obtained from MCE, and the model was then utilized to assess the bioactivity of 45 extant molecules.
Techniques: Injection, Imaging, Cell Culture, Staining, In Vitro, In Vivo
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