Key points are not available for this paper at this time.
The immunosuppressive tumor microenvironment in triple-negative breast cancer could hinder the response to thorough immunotherapy and diminish the antitumor efficacy. Although the STING pathway emerges as a promising target to remedy defects, uncertain drug delivery might lead to off-target inflammatory reactions. Here, we manifest a novel phototheranostic agent with an aggregation-induced emission property that guided the pharmacological activation of a STING agonist for photothermal immunotherapy to create an immunologically "hot" tumor. A pyridinium rotor strategy is proposed to develop a positively charged TBTP-Bz, which is stably coincorporated with a STING agonist MSA-2 into thermal-responsive exosome-liposome hybrid nanoparticles for tumor-targeting delivery. TBTP-Bz exhibits aggregation-enhanced NIR-II emission and a photoacoustic signal, accomplishing real-time tumor tracking. Its photothermal stimulation induces immunogenic cancer cell death and promotes the precise release of MSA-2, thus boosting STING activation and STING-mediated type I interferon production. Significantly, single-dose photoimmunotherapy effectively suppresses abscopal tumor growth and provokes an immune memory effect to inhibit postsurgical recurrent and rechallenged tumors. This demonstrates promising clinical potential for poorly immunogenic breast cancer.
Ning et al. (Thu,) studied this question.