NIR-II xanthene dyes with structure-inherent bacterial targeting for efficient photothermal and broad-spectrum antibacterial therapy

Development of novel broad-spectrum sterilization is an efficient strategy that can overcome drug resistance and avoid antibiotics abuse toward bacterial-infected diseases. Photothermal therapy (PTT) in the second near-infrared (NIR-II) therapeutic window with an increased tissue penetration and elevated maximal permissible exposure has attracted considerable attention in antibacterial applications. However, the lack of bacterial-targeted photothermal agents limits their further development. Herein, we developed three xanthene derivatives (CNs) with intense light harvesting ability around 1180 nm. Their bulky planar conformations facilitated the formation of H-aggregates with outstanding photothermal conversion ability and good photostability in the NIR-II therapeutic bio window. By manipulating side chains of CNs, their liposomes exhibited different surface charges, ranging from negative to positive. Remarkably, the intermolecular hydrogen bonding of CN3 dimer drived the positively charged xanthene skeleton exposed to the periphery, which endowed it natural bacterial targeting potency. Therefore, CN3 possessed a good NIR-II photothermal and broad-spectrum sterilization against Gram-positive and Gram-negative bacteria. The photothermal antibacterial activities for S. aureus and E. coli were 99.4% and 99.2%, respectively, promoting significant wound healing in bacteria-infected mice with superior biocompatibility. This structure-inherent bacterial targeting strategy as a proof-of-concept shows an efficient broad-spectrum bacterial inactivation, indicating more encouraging NIR-II photothermal antibacterial therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT) in the second near-infrared region (NIR-II, 1000-1700 nm) enables the treatment of deep inflammation more satisfactory due to higher tissue penetration depth. In this work, three new NIR-II xanthene derivatives (CNs) with intense light harvesting ability around 1180 nm were developed. CNs showed typical H-aggregated performance with bulky planar conformations and outstanding photothermal conversion ability. Density functional theory calculations revealed that the intermolecular hydrogen bonding of CN3 dimer drived the exposure of positively charged xanthene skeleton to periphery of dimer. Therefore, CN3 NPs possessed natural bacterial targeting potency and excellent NIR-II photothermal and broad-spectrum sterilization, and so as to significantly promote the wound healing of Gram-positive / negative bacteria infected mice.