Microwave thermal therapy (MWTT) is one of the most potent
ablative
treatments known, with advantages like deep penetration, minimal invasion,
repeatable operation, and low interference from bone and gas. However,
microwave (MW) is not selective against tumors, and residual tumors
after incomplete ablation will generate immunosuppression, ultimately
making tumors prone to recurrence and metastasis. Herein, a nano-immunomodulator
(Bi-MOF-l-Cys@PEG@HA, BMCPH) is proposed to reverse the immunosuppression
and reactivate the antitumor immune effect through responsively releasing
H2S in tumor cells for improving MWTT. Under MW irradiation,
BMCPH will mediate MWTT to ablate tumors and release l-cysteine
(l-Cys) to react with the highly expressed cystathionine
β-synthase in tumor to generate H2S. The generated
H2S can inhibit the accumulation of myeloid-derived suppressor
cells (MDSCs) and promote the expression of cytotoxic T lymphocytes
(CTLs). Moreover, Bi-MOF can also scavenge reactive oxygen species
(ROS), a major means of MDSCs-mediated immunosuppression, to further
weaken the immunosuppressive effect. Simultaneously, the surface-covered
HA will gather CTLs around the tumor to enhance the immune response.
This nano gas immunomodulator provides an idea for the sensitive and
tunable release of unstable gas molecules at tumor sites. The strategy
of H2S gas to reverse immunosuppression and reactivate
antitumor immune response introduces a direction to reduce the risk
of tumor recurrence and metastasis after thermal ablation.