Supramolecular Porphyrin Photosensitizers Based on Host−Guest Recognition for In Situ Bacteria‐Responsive Near‐Infrared Photothermal Therapy

Antibiotic resistance resulting from the overuse of antibiotics sets a high challenge for brutal antimicrobial treatment. Although photothermal therapy (PTT) overcomes the awkward situation of antibiotic resistance, it usually mistakenly kills the beneficial bacteria strains when eliminating pernicious bacteria. Specifically recognizing and damaging the target pathogens is urgently required for PTT-mediated sterilization strategy. Based on the host-guest recognition between cucurbit[10]uril (CB[10]) and porphyrins, two water-soluble supramolecular porphyrins are designed and implement selective bactericidal effect via in situ bacteria-responsive near-infrared (NIR) PTT. With the help of CB[10], the π-π stacking and hydrophobic interactions of porphyrins are efficiently inhibited, thus contributing to a good photostability and a high photothermal conversion efficiency. Attributing to the matching reduction potential between facultative anaerobic Escherichia coli (E. coli) and porphyrins, they are selectively in situ reduced into supramolecular phlorin and supramolecular chlorin by E. coli, successfully achieving a selective sterilization against E. coli. In vivo, the in situ bacteria-responsive NIR PTT systems also promote the quick recovery of E. coli-infected abscesses and trauma on mice without inducing obvious systemic toxicity, providing a new alternative to the current antibiotics and helping relieve the global public health crisis of abusive antibiotics.