Seeking and identifying time window of antibiotic treatment under in vivo guidance of PbS QDs clustered microspheres based NIR-II fluorescence imaging

Abstract

During bacterial infection, it is crucial to duly implement antibiotic treatment at a bottleneck time window when uncontrollable bacteria invasion exacerbates the condition. Here, we present a second near-infrared (NIR-II) fluorescence imaging strategy based on lead sulfide quantum dots clustered microspheres (PbS QDs@microspheres) to guide seeking and identifying the time window of antibiotic treatment. Our PbS QDs@microspheres with an average size of 510 nm were prepared through cross-linking process, demonstrating nine times higher photoluminescence (PL) intensity than the original PbS QDs, along with deep optical tissue penetration in muscle and 50% fat + 50% muscle. Notably, monitoring of bacterial infection in a mouse model of joint infection was successfully achieved by utilizing PbS QDs@microspheres to label staphylococcus aureus (S. aureus) in vivo, shown by a wave pattern of PL intensity lasting from 1 h to 3 d post-infection. Instructed by the NIR-II fluorescence signals from the intra-articularly injected S. aureus, 1 h to 3 d post-infection was sought to be a period of bacteria burst, along with relatively low immune cells count (neutrophils, B lymphocytes and T lymphocytes). On this basis, four therapeutic regimens (antibiotic administration at 1 h, 2 h, 1 d and 3 d post-infection) of antibiotic treatment were implemented to identify the time window, among which the 3 d group resulted in a survival rate of 50%, significantly lower than the other three groups (P = 0.028). Both the results of blood culture and histopathological analysis denoted that antibiotic administration at 3 d post-infection induced higher inflammatory reaction during the recovery period. In short, under the in vivo guidance of NIR-II fluorescence imaging based on our successfully prepared PbS QDs@microspheres, 1 h to 3 d post-infection was eventually identified as the time window of antibiotictreatment for joint infection of S. aureus in a mouse model. Thus, this study would further assist in deciphering precise therapeutic regimens during antibiotic treatment.