Nanoparticle‐Enhanced Radiotherapy to Trigger Robust Cancer Immunotherapy

Abstract

External radiotherapy is extensively used in clinic to destruct tumors by locally applied ionizing‐radiation beams. However, the efficacy of radiotherapy is usually limited by tumor hypoxia‐associated radiation resistance. Moreover, as a local treatment technique, radiotherapy can hardly control tumor metastases, the major cause of cancer death. Herein, core–shell nanoparticles based poly(lactic‐co‐glycolic) acid (PLGA) are fabricate, by encapsulating water‐soluble catalase (Cat), an enzyme that can decompose H2O2 to generate O2, inside the inner core, and loading hydrophobic imiquimod (R837), a Toll‐like‐receptor‐7 agonist, within the PLGA shell. The formed PLGA‐R837@Cat nanoparticles can greatly enhance radiotherapy efficacy by relieving the tumor hypoxia and modulating the immune‐suppressive tumor microenvironment. The tumor‐associated antigens generated postradiotherapy‐induced immunogenic cell death in the presence of such R837‐loaded adjuvant nanoparticles will induce strong antitumor immune responses, which together with cytotoxic T‐lymphocyte associated protein 4 (CTLA‐4) checkpoint blockade will be able to effectively inhibit tumor metastases by a strong abscopal effect. Moreover, a long term immunological memory effect to protect mice from tumor rechallenging is observed post such treatment. This work thus presents a unique nanomedicine approach as a next‐generation radiotherapy strategy to enable synergistic whole‐body therapeutic responses after local treatment, greatly promising for clinical translation.

Nanocatalytic Medicine

“…Although nanotechnology has been applied to modulate TME for overcoming such a limitation, there is still a large room for further improvement . Very recently, Chen et al have designed a catalytic strategy to relieve tumor hypoxia and modulate immunosuppressive TME for enhancing radiotherapy‐triggered immunotherapy ( Figure ) . In this work, they fabricated a PLGA‐based core–shell nanostructure by encapsulating CAT inside the inner core and R837 within the PLGA shell.…”

Immunomodulatory Nanosystems

“…[242] Hypoxia also helps prevent DNA damage and promote VEGFA production, leading to high tumor recurrence rate after radiotherapy. [164] The authors developed core-shell PLGA NPs by classical double emulsion method where catalase was encapsulated inside the hydrophilic core and imiquimod was loaded into the shell. [27] The catalase-nanoparticle and H 2 O 2 -NP were intravenously injected into mice successively at an interval of 4 h to enhance tumor oxygenation, which offered long-lasting effect to reduce the decomposition of endogenous H 2 O 2 , thus relieving the hypoxia burden in TME.…”

Enhancing Triple Negative Breast Cancer Immunotherapy by ICG‐Templated Self‐Assembly of Paclitaxel Nanoparticles

“…[58] The endoplasmic reticulum stress caused by intra cellular ROS generation could trigger CRT expression and trans portation onto the surface of the tumor cells. [58] The endoplasmic reticulum stress caused by intra cellular ROS generation could trigger CRT expression and trans portation onto the surface of the tumor cells.…”