No abstract

IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs) and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg) efficiently induces IL-23 secretion in a mannose receptor (MR)-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg) can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.

The tumor microenvironment significantly influences cancer progression and therapeutic response. Reprogramming of tumor microenvironment has emerged as a strategy to assist conventional cancer treatment. In recent years, photothermal therapy has received considerable attention owing to its noninvasiveness, high temporal–spatial resolution, and minimal drug resistance. Apart from ablating cancer cells by generating heat upon light irradiation, photothermal therapy can also affect the tumor microenvironment, such as disrupting the tumor extracellular matrix and tumor vasculature. Moreover, cancer cell death by hyperthermia could potentially activate the immune system to fight against tumor. In this topical review, we focus on the recent progress of photothermal therapy based on tumor microenvironment remodeling, aiming to better guide the design of nanoparticles for cancer photoimmunotherapy.

Organic photothermal nanoagents are promising candidates for treating primary tumors and inhibiting metastasis. However, they often exhibit poor photostability, low absorptivity, or limited photothermal conversion efficiency (PCE). Herein, a facile molecular engineering approach to produce efficient organic photothermal molecules is demonstrated. By integrating donoracceptor structure and molecular motors, a small molecule (TA1) is synthesized with large absorptivity (22.4 L g −1 cm −1 ), negligible reactive oxygen species generation, high PCE (84.8%), excellent photothermal stability, and good biocompatibility. Furthermore, microfluidics is used to thoroughly study the relationship between the size and process conditions, yielding small uniform nanoparticles (NPs) with a diameter of 44 nm. Importantly, TA1 NPs under near-infrared laser irradiation significantly suppressed primary breast tumor growth and metastasis, both in vitro and in vivo. This study shows that small organic molecule nanoparticles are promising candidates for future cancer nanomedicine.