Endometriosis (EM) results in pelvic adhesions and chronic inflammation, which significantly reduce embryo implantation and the clinical pregnancy rates of in vitro fertilization (IVF), affecting 190 million women worldwide. Traditional hormonal and surgical treatments alter ovarian and endometrial function, thereby hindering IVF. An urgent need exists for a localized treatment strategy that does not interfere with IVF procedures, aiming to enhance endometrial receptivity. To address this, we developed an innovative localized drug delivery system that simultaneously targets immune dysregulation and enhances endometrial function. This study reports a dual-drug delivery system based on poly(N-isopropylacrylamide) (PNIPAM) combined with nanocrystalline cellulose (CNC) for the local release of levonorgestrel (LNG) and botropase (BTP) to reprogram uterine natural killer cells and treat EM, overcoming previous drawbacks. The experimental results confirm stable CNC and PNIPAM structures and controlled the release of the composite drug. At concentrations of 0.5 mg/L LNG and 100 mg/L BTP, the release system achieved the highest CD16 – /CD16 + ratio and the most pronounced upregulation of autophagy-related molecules in uNK cells in our in vitro assays, indicating a shift in uNK cells toward an immune-tolerant state. In a mouse model of EM, the CNC–PNIPAM drug delivery system significantly improve endometrial receptivity. The CNC–PNIPAM drug delivery system demonstrates the medical potential of the local release of composite drugs, offering a new immunomodulatory approach for the treatment of EM and broader medical applications.
Ling Zhou,Xue-feng Tao,Li-sheng Tang,Ming-Bo Yang,Wei Yang
The incorporation of porous supporting materials to prepare shape-stable phase change materials (PCMs) is of great interest in recent years. However, extensive reported composite PCMs are shape-stable in the air atmosphere but neglected in the water environment. To develop shape-stable and waterproof PCMs is important for their outdoor applications but challenging. Herein, we report a novel cellulose nanocrystal/poly(N-isopropylacrylamide) (CNC/PNIPAM) gel-supported hexadecanol (H-anol) PCM with good thermal storage properties and excellent shape stability in both air and water environments. The CNC/PNIPAM hydrogel is prepared through an ultraviolet-induced C═C cross-linking reaction, and its physical structure and mechanical properties are well characterized. H-anol is then directly immerged into the CNC/PNIPAM alcogel by a facile and low-cost solvent-exchange strategy. The mechanism of the solvent-exchange strategy has been established. Because of the temperature-sensitive hydrophilic/hydrophobic transform behavior of the CNC/PNIPAM network, the CNC/PNIPAM/H-anol PCM displays excellent shape stability in a water environment by forming a dense hydrophobic surface, providing it with great potential in all-weather thermal energy storage applications.
危险品化学品经营许可证（带存储）