Wen Li,Zihan Zhang,Biyu Zhou,Yang Chen,Weijia Shen,Naiting Kuai,Jin Li
Serious vascular dysfunction and recurrent bacterial infection are critical obstacles in diabetic wound healing. Developing novel therapeutic strategies is crucial to address these challenges. Endothelial cell-derived apoptotic bodies (H-Abs), a novel type of extracellular vesicles with anti-inflammation and pro-angiogenesis properties, show great potential for diabetic wound treatment. Herein, a sprayable and thermosensitive in-situ forming composite gel based on poloxamer 407 (P407) was fabricated for the delivery of H-Abs camouflaged manganese dioxide nanozymes (BM), termed BM@H-Abs/TSCG-P407. In vitro and in vivo studies demonstrated that BM@H-Abs/TSCG-P407 undergoes a rapid sol-to-gel transformation in response to wound temperature during spraying treatment, thereby effectively covering irregularly shaped wounds. The incorporated H-Abs-camouflaged BM (BM@H-Abs) can effectively accelerate endothelial cell proliferation and migration, normalize oxygen supply, scavenge reactive oxygen species (ROS) accumulation, inhibit bacterial growth, and eventually enhance the healing of infected wounds in diabetic mice. These results indicate that BM@H-Abs/TSCG-P407 is a promising candidate for the treatment of diabetic wounds.
Microsatellite-stable colorectal cancer (MSS-CRC) exhibits resistance to programmed cell death protein-1 (PD-1) therapy. Improving the infiltration and tumor recognition of cytotoxic T-lymphocytes (CTLs) is a promising strategy, but it encounters huge challenges from drug delivery and mechanisms aspects. Here, a zeolitic imidazolate framework (ZIF) coated with apoptotic body membranes derived from MSS-CRC cells is engineered for the co-delivery of ginsenoside Rg1 (Rg1) and atractylenolide-I (Att) to MSS-CRC, named as Ab@Rg1/Att-ZIF. This system is selectively engulfed by Ly-6C + monocytes during blood circulation and utilizes a “hitchhiking” mechanism to migrate toward the core of MSS-CRC. Ab@Rg1/Att-ZIF undergoes rapid disassembly in the tumor, released Rg1 promotes the processing and transportation of tumor antigens in dendritic cells (DCs), enhancing their maturation. Meanwhile, Att enhances the activity of the 26S proteasome complex in tumor cells, leading to increased expression of major histocompatibility complex class-I (MHC-I). These coordinated actions enhance the infiltration and recognition of CTLs in the center of MSS-CRC, significantly improving the tumor inhibition of PD-1 treatment from ≈5% to ≈69%. This innovative design, involving inflammation-guided precise drug co-delivery and a rational combination, achieves synergistic engineering of the tumor microenvironment, providing a novel strategy for successful PD-1 treatment of MSS-CRC.
危险品化学品经营许可证（带存储）