A Booster for Radiofrequency Ablation: Advanced Adjuvant Therapy via In Situ Nanovaccine Synergized with Anti-programmed Death Ligand 1 Immunotherapy for Systemically Constraining Hepatocellular Carcinoma

Abstract

Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for treating hepatocellular carcinoma (HCC), which could destroy tumors through hyperthermia and generate massive tumor-associated antigens (TAAs). However, residual malignant tissues or small satellite lesions are hard to eliminate, generally resulting in metastases and recurrence. Herein, an advanced in situ nanovaccine formed by layered double hydroxides carrying cGAMP (STING agonist) (LDHs-cGAMP) and adsorbed TAAs was designed to potentiate the RFA-induced antitumor immune response. As-prepared LDHs-cGAMP could effectively enter cancerous or immune cells, inducing a stronger type I interferon (IFN-I) response. After further adsorption of TAAs, nanovaccine generated sustained immune stimulation and efficiently promoted activation of dendritic cells (DCs). Notably, infiltrations of cytotoxic lymphocytes (CTLs) and activated DCs in tumor and lymph nodes were significantly enhanced after nanovaccine treatment, which distinctly inhibited primary, distant, and metastasis of liver cancer. Furthermore, such a nanovaccine strategy greatly changed the tumor immune microenvironment and promoted the response efficiency of anti-programmed death ligand 1 (αPD-L1) immunotherapy, significantly arresting the poorly immunogenic hepa1–6 liver cancer progression. These findings demonstrate the potential of nanovaccine as a booster for RFA in liver cancer therapy and provide a promising in situ cancer vaccination strategy.

Advances of Layered Double Hydroxide‐Based Materials for Tumor Imaging and Therapy

“…The prepared LDH-cGAMP can effectively enter cancer cells or immune cells, induce stronger IFN-I response, and promote the activation of dendritic cells (DCs). [173] In addition, Pan et al prepared Fe/Ni-LDH for enhancing apoptosis and iron sag-induced cancer nano-therapy, and explored its potential anti-tumor mechanism. [174] Although LDH-based nanocomposites show promising applications in the field of tumour diagnostics and therapeutics, they still face a series of challenges before clinical application.…”

Sensitize Tumor Immunotherapy: Immunogenic Cell Death Inducing Nanosystems

“… CT26 (Balb/c mice) [ 161 ] UCNP+ Indocyanine green (ICG) + Bengal (RB) + DSPE-PEG-mal CRT, HMGB1, TNF-α, IL-6, IL-12 ↑DCs maturation; ↑CD8 + T cells Increased tumour protein antigen capture: PDT and PTT combination therapy 4T1 (Balb/c mice) [ 162 ] UCNP +TPEBTPy CRT, HSP70, HMGB1, IFN-γ ↑DCs maturation; ↑CD4 + , CD8 + T cells Different functions of nanoparticles by controlling near-infrared light intensity B16F10 (C57BL/6 mice) [ 163 ] LDHs LDHs+ 2’,3’-cyclic guanosine adenosine monophosphate IFN-γ and CXCL10 ↑DCs maturation; ↑CD8 + T cells and NK cells As-prepared LDHs-cGAMP could effectively enter cancerous or immune cells, inducing a stronger type I interferon (IFN-I) response. Hepa1-6 (C57BL/6 mice) [ 164 ] FeOOH+Cu-LDHs+ STA-9090 CRT, Hsp90 ↑CD3 + , CD8 + T cells; Sensitisation to photothermal therapy by overexpression of HSP90; amplification of ROS production by PTT in combination with CDT 4T1 (Balb/c mice) [ 165 ] …”

“…Chen et al prepared RFA-based LDHs-cGAMP complexes, which effectively promoted DCs activation to inhibit the progression of poorly immunogenic hepa1-6 hepatocellular carcinomas by activating the cGAS-STING pathway and adsorbing RFA-generated TAAs, generating sustained immune stimulation ( Figure 6 ). 164 , 187 Achieving effective ablation of tumours through PTT requires raising the temperature of cancerous tissue above 45°C. However, the repair of thermogenic (38–42°C) cell damage by Hsp, which are overexpressed by cancer cells, poses a challenge.…”

A Side-Effect-Free Interventional Therapy for Precisely Eliminating Unresectable Cancer Pain

“…Taken together, a nonaddictive, long-lasting, safe, and efficient approach to removing advanced cancer pain is elusive currently. ,,,,, Eradicating locoregional tumors and cancer pain safely remains a significant challenge. − Therefore, to surmount the above-mentioned challenges, we developed another IAT termed nanoparticle-mediated microknife (NP-MK) ablation to locoregionally eliminate cancer pain as well as tumors. This IAT system was composed of self-assembled nanoparticles (NPs), infusion catheters, puncture needles, injection pump, and an empirical tumor ablation formula.…”