H₂S-Reactivating Antitumor Immune Response after Microwave Thermal Therapy for Long-Term Tumor Suppression

Abstract

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.

Acid-Triggered Degradation of Three-In-One Ag2S Quantum Dots for In Situ Ratiometric NIR-II Fluorescence Imaging-Guided Ion/Gas Combination Therapy

“…Because both Ag + and H 2 S are cytotoxic to tumor cells, , the acid-triggered Ag 2 S QD degradation was attempted for in situ therapy of tumors. To verify this hypothesis, the intracellular H 2 S gas production was first tested using the commercial Washington State Probe-5 (WSP-5) by culturing 4T1 cells (a mouse breast cancer cell line) into the 1640 medium containing 0.25 mM DCNP@Ag 2 S QDs . Under the normal physiological (pH 7.4) conditions, the DCNP@Ag 2 S QDs remained stable, evidenced by the comparable amount of intracellular H 2 S to that of the blank group (the upper panel, Figure A).…”

Tunable Zeolitic Imidazolate Framework‐8 Nanoparticles for Biomedical Applications

“…Therefore, there has been a growing emphasis on combination therapy strategies, which hold the promise of achieving additive and/or synergistic antitumor effects by integrating two or more treatment modalities. [176,177] The versatility of design, synthesis, and modification options of ZIF-8 make it as highly DOX@ZIF-8 Dox Chemotherapy [154] RhB@ZIF-8 Rhodamine B (RhB) ATP Sensing [155] ZIF-8@Ce6-HA Ce6 PDT [77] Bi@ZIF-8 Bi PTT [156] HZ@GD DNAzyme down-regulate GLUT1 expression [157] ZIF-8/DOX@ZrO 2 @IL DOX, ZrO 2 , IL Chemo-microwave Thermal therapy [158] BSA-MnO 2 / Ce6@ZIF-8…”

Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer

“…However, the nonselectivity of MW irradiation makes it still a challenge to completely ablate a tumor lesion while ensuring the safety of adjacent normal tissue, especially for these large or irregularly shaped tumors, ultimately resulting in tumor residual and recurrence . To further expand the clinical application potential of MWT, a series of MW sensitizers with the aim of enhancing MW heating efficiency of tumor sites have been developed. − The heating principle of these MW sensitizers was mostly based on the ion confinement effect, a mechanism whereby the movement of ions within the confined space provided by the MW sensitizer is accelerated under MW irradiation to generate kinetic energy for further conversion into heat . Though they can improve the MW thermal effect of a tumor to a certain extent after being enriched in tumor sites, the uniformity of the induced thermal damage is still greatly limited by the ionic state within the cell, such as the concentration and the distribution of ions. − Recently, MW absorbing materials (MAMs), as a class of materials that can essentially promote the energy conversion between electromagnetic energy and thermal energy to generate excellent thermal effects, have attracted increasing attention and shown the potential to solve the limitations of existing MW thermal sensitizers. − Regrettably, the absorption frequencies of most MAMs are mainly distributed in the mid- and high-frequency bands, − and few have been reported to achieve strong microwave absorption (MA) performance at medical frequencies (433, 915, and 2450 MHz) .…”