Selective thermotherapy of tumor by self-regulating photothermal conversion system.

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.

Binding of the polysaccharide from Acanthopanax giraldii Harms to toll-like receptor 4 activates macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine, Acanthopanax giraldii Harms, is commonly used to treat arthralgia due to wind, cold and dampness, as well as weakness in the feet and knees. Its other reported effects include eliminating flatulence, strengthening muscles and bones, and delaying aging. The polysaccharides in A. giraldii Harms are the major bioactive substances that confer the herb's antioxidant properties as well as anticancer and antiviral effects. AIMS OF THE STUDY: To elucidate the underlying mechanism and signaling cascade involved in the homogeneous A. giraldii Harms polysaccharide II (AHP-II)-mediated immunomodulation of mice macrophages. MATERIALS AND METHODS: The phagocytosis of neutral red and the production of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were measured to determine AHP-II-induced macrophage activation. Confocal microscopy and flow cytometry were used to confirm the binding of AHP-II to macrophages. The involvement of Toll-like receptor (TLR) 4 in AHP-II-induced macrophage activation was demonstrated using antibody blocking and macrophages from C3H/HeJ TLR4-mutant mice. Western blotting was used to map AHP-II-induced downstream signaling pathways. RESULTS: AHP-II increased the phagocytosis of macrophages and the release of nitric oxide, IL-6 and TNF-α cytokines. Direct, saturable and reversible binding of AHP-II to macrophages was observed, while it can be inhibited by the anti-TLR4 antibody. In addition, the presence of the anti-TLR4 antibody inhibited AHP-II-induced macrophage IL-6 and TNF-α production in the peritoneal macrophages of C3H/HeJ mice. Moreover, AHP-II-TLR4-stimulated macrophages activate the downstream intracellular ERK and JNK/nuclear factor (NF)-κB signaling pathways. In addition, the AHP-II-mediated regulation of IL-6 and TNF-α production from macrophages was greatly affected by specific ERK, JNK and NF-κB inhibitors. CONCLUSION: Our study elucidated the immunomodulatory mechanism of AHP-II in macrophage activation and identified TLR4 as the main receptor coordinating AHP-II binding. Our findings suggest AHP-II may be used as a novel immunopotentiator for medical purposes.