Patients with ulcerative colitis (UC) often loss responses over long term usage of conventional therapies. Tofacitinib, a pan-Janus kinases (JAK) inhibitor is approved for moderate to severe UC treatment, while dose-limiting systemic side effects including infections, cancers and lymphoma limit its popularity of clinical application. This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1 (anti-MAdCAM-1) antibody modified reactive oxygen species (ROS) responsive human serum albumin-based nanomedicine denoted as THM, to improve the therapeutic efficacy of tofacitinib for UC treatment. THM has the drug releasing properties in response to ROS stimulation. In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages. Meanwhile, the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing. In addition, in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon. Moreover, THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis. This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.

Rheumatoid arthritis (RA) is a long-term inflammatory disease derived from an autoimmune disorder of the synovial membrane. Current therapeutic strategies for RA mainly aim to hamper the macrophages' proliferation and reduce the production of pro-inflammatory cytokines. Therefore, the accumulation of therapeutic agents targeted at the inflammatory site should be a crucial therapeutic strategy. Nowadays, the nanocarrier system incorporated with stimuli-responsive property is being intensively studied, showing the potentially tremendous value of specific therapy. Stimuli-responsive (i.e., pH, temperature, light, redox, and enzyme) polymeric nanomaterials, as an important component of nanoparticulate carriers, have been intensively developed for various diseases treatment. A survey of the literature suggests that the use of targeted nanocarriers to deliver therapeutic agents (nanotherapeutics) in the treatment of inflammatory arthritis remains largely unexplored. The lack of suitable stimuli-sensitive polymeric nanomaterials is one of the limitations. Herein, we provide an overview of drug delivery systems prepared from commonly used stimuli-sensitive polymeric nanomaterials and some inorganic agents that have potential in the treatment of RA. The current situation and challenges are also discussed to stimulate a novel thinking about the development of nanomedicine.

Seeking profitable therapies for triple-negative breast cancer (TNBC) has attracted intense research interest. However, an efficient cure for TNBC remains an unresolved challenge in oncology. Herein, for the first time, we describe the use of polymeric nanoparticles loaded with NVP-BEZ235 and Chlorin-e6, denoted as NVP/Ce6@NPs, to overcome the adaptive treatment tolerance of TNBC by taking advantage of the synergistic effect between biochemical and photodynamic therapies. Upon laser irradiation, the NVP/Ce6@NPs generated reactive oxygen species (ROS) and efficiently induced the apoptosis of tumor cells through DNA damage. Furthermore, the released NVP-BEZ235 could prevent Chk1 phosphorylation-induced DNA damage repair, thus enhancing the sensitivity of tumor cells to ROS. Animal studies on mice bearing an MDA- MB-231 tumor validated that the NVP/Ce6@NPs had a greater therapeutic efficacy compared to that of monotherapies, with an inhibition ratio of 89.3%. Western blotting and cell viability analyses confirmed the inhibition of both MDA-MB-231 cell proliferation and Chk1 phosphorylation by NVP/Ce6@NPs. These findings provide a rational understanding of the synergistic effect of the biochemical/photodynamic therapy and pave the way for the development of efficient therapeutic approaches to fight against TNBC.