Bacterial targeted AIE photosensitizers synergistically promote chemotherapy for the treatment of inflammatory cancer

Abstract

Tumor-associated components, especially extratumoral bacteria (EB) in the form of biofilms, could exacerbate cancer progression and hinder the effectiveness of antitumor drugs by covering the interstitial tumor space. Although photodynamic therapy (PDT) is a promising modality to kill cancer cells and bacteria with high spatiotemporal precision, the low penetration of light limits its potential in deep tumor therapy. Furthermore, current 2D culture-based preclinical in vitro models failed to reflect the complexity of the tumor microenvironment. Here, we developed an unprecedented “1 + 1 > 2″ combinatorial strategy of PDT and chemotherapy by co-delivering a bacterial-targeted photosensitizer with aggregation-induced emission (AIE) property and an anticancer drug, doxorubicin. The theranostic system could selectively visualize and rapidly kill EB, using a microfluidic-based 3D bladder cancer model. The effect of combinatorial therapy was synergistic, resulting in improved efficacy, as evidenced by at least a 2.5-fold reduction in the half-maximal inhibitory concentration of doxorubicin. Validation using a fish wound infection model further demonstrated the feasibility of AIE photosensitizers for efficient fluorescence imaging-guided PDT in vivo. Overall, we proposed a robust AIE PDT/chemotherapy strategy that shows great potential for rapid and concurrent treatment of bacterially infected cancer patients.