ROS‐Responsive Core‐Shell Microneedles Based on Simultaneous Efficient Type I/II Photosensitizers for Photodynamic Against Bacterial Biofilm Infections

Abstract

Antimicrobial photodynamic therapy (aPDT) has emerged as an appealing therapeutic option against biofilm infections. However, effectively penetrating the dense barrier of biofilm and anchoring bacteria to achieve biofilm elimination and wound healing under hypoxic environments remains a challenge for aPDT. Herein, three type I/II Hypocrellin B (HB)‐cationic photosensitizers (HB‐P, HB‐TP, and HB‐TTP) are designed based on a multi‐cationic long chains molecular engineering strategy. With an increasing number of introduced cations, the reactive oxygen species (ROS) production and bacterial‐anchoring abilities of HB‐cationic photosensitizers are greatly enhanced. Notably, HB‐TTP demonstrates higher type I/II aPDT activity and broad‐spectrum antibacterial properties. Furthermore, to effectively address the conundrum of healing biofilm‐infected wounds, a ROS‐responsive core‐shell microneedle (HB‐TTP&EGF@MN) is designed by biphasically integrating HB‐TTP and growth factor. When the microneedle penetrates biofilm, the shell quickly dissolves and releases HB‐TTP to achieve biofilm removal under laser irradiation. The core is subsequently degraded slowly in the presence of endogenous ROS within the wound, facilitating a sustained release of growth factor to promote wound tissue regeneration. This work not only provides an effective strategy for the rational design of efficient antimicrobial agents but also proposes innovative ideas for the development of controlled‐release pharmaceutical materials to synergize against biofilm infections.