Transient Mild Photothermia Improves Therapeutic Performance of Oral Nanomedicines with Enhanced Accumulation in The Colitis Mucosa.

The treatment outcomes of oral medications against ulcerative colitis (UC) have long been restricted by low drug accumulation in the colitis mucosa and subsequent unsatisfactory therapeutic efficacy. Here, we constructed high-performance pluronic F127 (P127)-modified gold shell (AuS)-polymeric core nanotherapeutics loading with curcumin (CUR). Under near-infrared irradiation, the resultant P127-AuS@CURs generated transient mild photothermia (TMP; ∼42°C, 10 min), which facilitated their penetration through colonic mucus and favored multiple cellular processes, including cell internalization, lysosomal escape, and controlled CUR release. This strategy relieved intracellular oxidative stress, improved wound healing, and reduced immune responses by polarizing the pro-inflammatory M1-type macrophages to the anti-inflammatory M2-type. Upon oral administration of hydrogel-encapsulating P127-AuS@CURs plus intestinal intra-lumen TMP, their therapeutic effects against acute and chronic UC are demonstrated to be superior to those of a widely used clinical drug, dexamethasone. The treatment of P127-AuS@CURs (+ TMP) elevated the proportions of beneficial bacteria (e.g., Lactobacillus and Lachnospiraceae), whose metabolites could also mitigate colitis symptoms by regulating genes associated with anti-oxidation, anti-inflammation, and wound healing. Overall, the intestinal intra-lumen TMP offers a promising approach to enhance the therapeutic outcomes of noninvasive medicines against UC. This article is protected by copyright. All rights reserved.