Aim: To investigate whether resveratrol (RSV) can improve non‐alcoholic fatty liver disease (NAFLD) and to find the possible mechanism. Methods: Rats fed a high‐fat diet were treated with RSV. The liver histology was observed. Hyperinsulinemic euglycemic clamp was performed to assess insulin sensitivity. Fat accumulation was induced in HepG2 cells, and the cells were treated with RSV. AMP‐activated protein kinase (AMPK) phosphorylation levels were determined both in the animal study and cell study. Results: Rats fed a high‐fat diet developed abdominal obesity, NAFLD, and insulin resistance (IR), which were markedly improved by 10 weeks of RSV administration. RSV treatment prevented triacylglycerol (TG) accumulation in HepG2 cells that were incubated with high concentration of glucose and insulin. Both in vivo and in vitro studies showed that RSV treatment could promote the phosphorylation of AMPK, which in this study, suppressed 2 lipogenesis gene expressions, contributing to the improvement of NAFLD and IR. Conclusion: The results indicated that by reducing TG accumulation and improving IR, RSV could protect the liver from NAFLD. The activation of AMPK was involved in the mechanism. RSV has the therapeutic potential for preventing or treating NAFLD and IR‐related metabolic disorders.

Immunotherapy has recently become a promising strategy for the treatment of a wide range of cancers. However, the broad implementation of cancer immunotherapy suffers from inadequate efficacy and toxic side effects. Integrating pH-responsive nanoparticles into immunotherapy is a powerful approach to tackle these challenges because they are able to target the tumor tissues and organelles of antigen-presenting cells (APCs) which have a characteristic acidic microenvironment. The spatiotemporal control of immunotherapeutic drugs using pH-responsive nanoparticles endows cancer immunotherapy with enhanced antitumor immunity and reduced off-tumor immunity. In this review, we first discuss the cancer-immunity circle and how nanoparticles can modulate the key steps in this circle. Then, we highlight the recent advances in cancer immunotherapy with pH-responsive nanoparticles and discuss the perspective for this emerging area.

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