Zhao Zinan, Xu Yao, Hu Yong
Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, P. R. China.
Nat Commun. 2025 Apr 22;16(1):3778. doi: 10.1038/s41467-025-59172-9.
Microcapsules composed of synthetic polymeric matrices have attracted considerable attention in delivering oral probiotics. However, existing polymeric microcapsules demonstrate inadequate acid resistance and adaptability, as well as deficiency in the inflamed colon-specificity and uncontrolled release of probiotics therein. Herein, a DNA microcapsule is prepared as a probiotic-transporting micromotor through photo-crosslinking of hyaluronic acid methacrylate and acrydite-modified A-/C-rich oligomers within the microfludically generated droplets in the presence of nitric oxide-cleavable crosslinker and gas donor manganese carbonyl (MnCO). As the microcapsules traverse stomach, duodenum, and ultimately colon, the formation and dissociation of A-motif and i-motif structures instigate a reversible shrinking-swelling transition of microcapsules to preserve probiotic viability. Subsequently, the microcapsules exhibit chemotaxis towards inflamed colon site, driven by a gas-generating reaction between MnCO and elevated reactive oxygen species. Following disintegration of the microcapsules, triggered by endogenous nitric oxide, probiotics are released to reshape the dysbiosis of intestinal microflora. This advanced delivery system offers significant promise for the effective clinical management of inflammatory bowel disease.
由合成聚合物基质组成的微胶囊在口服益生菌递送方面引起了相当大的关注。然而，现有的聚合物微胶囊表现出抗酸性和适应性不足，以及在炎症结肠特异性和益生菌在其中的不受控释放方面的缺陷。在此，通过在一氧化氮可裂解交联剂和气体供体羰基锰（MnCO）存在下，在微流控产生的液滴中对甲基丙烯酸透明质酸和丙烯酸盐修饰的富含A/C的寡聚物进行光交联，制备了一种作为益生菌运输微马达的DNA微胶囊。当微胶囊穿过胃、十二指肠并最终到达结肠时，A基序和i基序结构的形成和解离促使微胶囊发生可逆的收缩-膨胀转变，以保持益生菌的活力。随后，在MnCO与升高的活性氧之间的产气反应驱动下，微胶囊向炎症结肠部位表现出趋化性。在内源性一氧化氮引发微胶囊解体后，益生菌被释放出来，以重塑肠道微生物群的失调。这种先进的递送系统为炎症性肠病的有效临床管理提供了巨大的前景。
