Role of Immunosuppressive Microenvironment in Acquiring Immunotolerance Post-Photothermal Therapy

BACKGROUND: Nanoparticle-mediated photothermal therapy (PTT) has been well studied as a treatment for cancer. However, the therapeutic outcome of PTT is often hindered by the penetration depth of laser light. In the tumor margin beyond the laser penetration limit, tumor recurrence often occurs, bypassing the immune response of the host. Accumulating evidence suggests the prominent role of tumor microenvironment (TME) and its interactions with the immune components contribute to an immunosuppressive milieu during the post-therapy period. Here, we explored the immunosuppressive cascade generated after PTT, which is responsible for tumor recurrence, and identified the potential targets to achieve an effective PTT period. METHODS: Here, we investigated the immunosuppressive cascade generated after PTT in a CT26 tumor bearing mouse. The liposomal system loaded with the indocyanine green (ICG) was utilized for the generation of PTT with high efficiency. Immunological factors such as cytokines and protein expressions post-therapy were investigated through enzyme-linked immunosorbent assay, flow cytometry and western blot analysis. RESULTS: Our results suggested that PTT with ICG-loaded liposomes (Lipo-ICG) was effective for the first 5 days after treatment, resulting in tumor suppression. However, an immunosuppressive and pro-inflammatory environment developed thereafter, causing the recruitment and upregulation of the immune evasion factors of heat shock protein 70, programmed death ligand 1, indoleamine-dioxygenase, interleukin-6, transforming growth factor-β, regulatory T-cells, and myeloid-derived suppressor cells, to develop immunotolerance. CONCLUSION: Collectively, these findings have determined potential therapeutic targets to modulate the TME during PTT and achieve tumor ablation without remission.

Biopolymeric In Situ Hydrogels for Tissue Engineering and Bioimaging Applications

BACKGROUND: Biopolymeric in situ hydrogels play a crucial role in the regenerative repair and replacement of infected or injured tissue. They possess excellent biodegradability and biocompatibility in the biological system, however only a few biopolymeric in situ hydrogels have been approved clinically. Researchers have been investigating new advancements and designs to restore tissue functions and structure, and these studies involve a composite of biometrics, cells and a combination of factors that can repair or regenerate damaged tissue. METHODS: Injectable hydrogels, cross-linking mechanisms, bioactive materials for injectable hydrogels, clinically applied injectable biopolymeric hydrogels and the bioimaging applications of hydrogels were reviewed. RESULTS: This article reviews the different types of biopolymeric injectable hydrogels, their gelation mechanisms, tissue engineering, clinical applications and their various in situ imaging techniques. CONCLUSION: The applications of bioactive injectable hydrogels and their bioimaging are a promising area in tissue engineering and regenerative medicine. There is a high demand for injectable hydrogels for in situ imaging.