Heat‐Confined Tumor‐Docking Reversible Thermogel Potentiates Systemic Antitumor Immune Response During Near‐Infrared Photothermal Ablation in Triple‐Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) features immunologically "cold" tumor microenvironments with limited cytotoxic T lymphocyte (CTL) infiltration. Although ablation therapies have demonstrated modulation of "cold" TNBC tumors to inflamed "hot" tumors, recruitment of myeloid derived suppressor cells (MDSCs) at the tumors post ablation therapies prevents the infiltration of CTLs and challenge the antitumor potentials of T-cell therapies. Here, a thermal ablation immunotherapy strategy is developed to prevent the immune suppressive effects of MDSCs during photothermal ablation and induce a durable systemic antitumor immunity to eradicate TNBC tumors. An injectable pluronic F127/hyaluronic acid (HA)-based hydrogel embedded with manganese dioxide (BM) nanoparticles and TLR7 agonist resiquimod (R848) (BAGEL-R848), is synthesized to induce in situ laser-assisted gelation of the hydrogel and achieve desired ablation temperatures at a low laser-exposure time. Upon 808-nm laser irradiation, a significant reduction in the tumor burden is observed in BAGEL-R848-injected 4T1 tumor-bearing mice. The ablation induced immunogenic cell death and sustained release of R848 from BAGEL-R848 promotes dendritic cell maturation and reduced MDSCs localization in tumors. In addition, inflammatory M1 macrophages and CD8+IFN+ CTL are enriched in distant tumors in bilateral 4T1 tumor model, preventing metastatic tumor growth and signifying the potential of BAGEL-R848 to treat TNBC.

A sugar modified amphiphilic cationic nano-adjuvant ceased tumor immune suppression and rejuvenated peptide vaccine induced antitumor immunity in cervical cancer

“…Previously, we demonstrated that R848 can significantly reduce the MDSC population in primary and secondary 4T1 breast cancer tumors. 17 In the present study, MDSCs were significantly reduced in the primary (Fig. S15B and S18†) and secondary tumors (Fig.…”

“…14 Recent studies have demonstrated that R848 can modulate the tumor microenvironment by inducing macrophage repolarization and enhancing dendritic cell maturation to activate cytotoxic T lymphocytes and induce anti-tumor activity. 15–18 Rodell et al have shown that crosslinked beta cyclodextrin loaded R848 nanoparticles can enhance antitumor immunity by polarizing TAMs to M1 inflammatory macrophages. 19 Previously, we demonstrated that R848 administration in triple-negative breast cancer can reduce myeloid-derived suppressor cells (MDSCs) and enhance CD8+ T cell populations in primary and secondary tumors during photothermal therapy.…”

“…19 Previously, we demonstrated that R848 administration in triple-negative breast cancer can reduce myeloid-derived suppressor cells (MDSCs) and enhance CD8+ T cell populations in primary and secondary tumors during photothermal therapy. 17…”

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

“…In addition, photonic hyperthermal-assisted immunotherapy could perform immunoadjuvant-like effects to mobilize tumor-attacking immunity [ 194 , 195 ]. The common photothermal immunomodifiers consist of Au-derived nanomaterials, near-infrared (NIR) dye small molecules and others [ 196 , 197 ].…”

Thermosusceptible Nitric-Oxide-Releasing Nitrogel for Strengthening Antitumor Immune Responses with Tumor Collagen Diminution and Deep Tissue Delivery during NIR Laser-Assisted Photoimmunotherapy

“…Nanoparticle-mediated photothermal therapy (PTT) has emerged in recent years for local tumor ablation, tumor growth arrest, and activating antitumor immune responses. , The use of organic compounds and nanoparticles in near-infrared (NIR) laser-irradiated PTT is an effective therapeutic strategy for antitumor therapy. − The application of PTT-mediated thermal ablation to tumor tissues at mild temperatures induces immunogenic cell death (ICD), which releases danger-associated molecular patterns (DAMPs). For example, calreticulin expression in cancer cells alters antitumor immune responses via antigen presentation. − However, the therapeutic results are limited because of the inability of light to effectively penetrate large tumors as well as inadequate thermal ablation, both of which cause tumor relapse and regrowth.…”