Bacteria-driven nanosonosensitizer delivery system for enhanced breast cancer treatment through sonodynamic therapy-induced immunogenic cell death.

BACKGROUND: Sonodynamic therapy (SDT) has shown promise as a non-invasive cancer treatment due to its local effects and excellent tissue penetration. However, the limited accumulation of sonosensitizers at the tumor site hinders its therapeutic efficacy. Although nanosonosensitizers have improved local tumor accumulation through passive targeting via the enhanced permeability and retention effect (EPR), achieving sufficient accumulation and penetration into tumors remains challenging due to tumor heterogeneity and inaccurate targeting. Bacteria have become a promising biological carrier due to their unique characteristic of active targeting and deeper penetration into the tumor. METHODS: In this study, we developed nanosonosensitizers consisting of sonosensitizer, hematoporphyrin monomethyl ether (HMME), and perfluoro-n-pentane (PFP) loaded poly (lactic-co-glycolic) acid (PLGA) nanodroplets (HPNDs). These HPNDs were covalently conjugated onto the surface of Escherichia coli Nissle 1917 (EcN) using carbodiimine chemistry. EcN acted as an active targeting micromotor for efficient transportation of the nanosonosensitizers to the tumor site in triple-negative breast cancer (TNBC) treatment. Under ultrasound cavitation, the HPNDs were disrupted, releasing HMME and facilitating its uptakes by cancer cells. This process induced reactive oxygen species (ROS)-mediated cell apoptosis and immunogenic cell death (ICD) in vitro and in vivo. RESULTS: Our bacteria-driven nanosonosensitizer delivery system (HPNDs@EcN) achieved superior tumor localization of HMME in vivo compared to the group treated with only nanosonosensitizers. This enhanced local accumulation further improved the therapeutic effect of SDT induced-ICD therapeutic effect and inhibited tumor metastasis under ultrasound stimulation. CONCLUSIONS: Our research demonstrates the potential of this ultrasound-responsive bacteria-driven nanosonosensitizer delivery system for SDT in TNBC. The combination of targeted delivery using bacteria and nanosonosensitizer-based therapy holds promise for achieving improved treatment outcomes by enhancing local tumor accumulation and stimulating ICD.

Immunogenic sonodynamic therapy for inducing immunogenic cell death and activating antitumor immunity.

Immunotherapy is widely regarded as a promising treatment for cancer. However, the immune effector phase suppression of tumor microenvironment (TME) and the generation of immune-related adverse events limit its application. Research indicates that sonodynamic therapy (SDT) can effectively activate antitumor immunity while killing tumor cells. SDT produces cytotoxic substances of tumors, and then cell apoptosis and immunogenic death occur by selectively activating the sonosensitizer under ultrasound. In recent years, various SDT alone as well as SDT in combination with other therapies have been developed to induce immunogenic cell death (ICD) and enhance immunotherapy. This paper overviews the research progress of SDT and nanotechnology in recent years, including the strategies involving SDT alone, SDT-based synergistic induction of antitumor immunity, and immunotherapy based on SDT for multimodal immunotherapy. Finally, the prospects and challenges of these SDT-based therapies in cancer immunotherapy are discussed.