Small. 2026 Oct 22:e76426. doi: 10.1002/smll.76426. Online ahead of print.
ABSTRACT
Drug-resistant bacterial infections seriously threaten public health, and the formation of a biofilm barrier plays an important role. Drug-resistant biofilms are difficult to remove because the penetration and specificity of traditional antimicrobial drugs are poor, and the microenvironment in the inner layer of biofilms is hypoxic. Herein, we developed activatable aptamer-functionalized pro-photosensitizers (APMB) by modifying the clinical photosensitizer methylene blue (MB) with an aptamer that can specifically bind to drug-resistant bacteria. The APMB can simultaneously achieve imaging-guided efficient anti-infection and biofilm destruction, thereby increasing the therapeutic efficiency of the treatment of bacterial biofilm infections. Additionally, we co-loaded APMB and the antibiotic metronidazole (MNZ) into hydrogels to prepare a degradable microneedle patch, which can utilize photodynamic effects to eliminate biofilms under normoxic conditions and potentiate the hypoxic microenvironment to activate the antibacterial activity of MNZ, ultimately resulting in the synergistic killing of deep-seated bacteria. To summarize, this simple and intelligent phototheranostic molecular platform improves deep anti-infection efficacy through the synergistic effect of sequential activation while decreasing systemic toxicity, thereby providing a promising avenue for clinical translation to combat antimicrobial resistance.
PMID:42912835 | DOI:10.1002/smll.76426