The delivery of drugs across the blood–brain barrier (BBB) effectively and safely is one of the major challenges in the treatment of neurodegenerative diseases.

Methotrexate (MTX) is a drug that is used for the clinical treatment of rheumatoid arthritis (RA), a stubborn disease caused by over-immunization. However, the toxicity that arises as a result of poor selectivity to inflammatory cells severely limits the application of MTX. Therefore, new therapeutic strategies are needed for treating RA. Here, we describe the design and synthesis of a nanotherapy agent, Pd-Cys@MTX@RGD, which can target inflammatory cells and control MTX release. The novel hexagonal palladium (Pd) nanosheets were used as a near-infrared (NIR) photothermal agent modified with arginine-glycineaspartic acid (RGD) peptides on the surface to enhance the ability of the nanosheet targeting of inflammatory cells. In subsequent experiments, the Pd-Cys@MTX@RGD nanosheets were observed to greatly reduce the toxicity of MTX, showing controlled MTX release under irradiation of 808 nm (0.3 W cm⁻²). Moreover, taking advantage of the fact that MTX can be combined with multiple therapeutic methods, the photothermal therapy (PTT) of Pd nanosheets provided a compensatory effect to enhance the therapeutic efficacy of MTX. Under combination therapy, Pd-Cys@MTX@RGD was shown to effectively inhibit the inflammatory response induced by vascular endothelial growth factor (VEGF) and IL-1β. And, in vivo, multifunctional Pd-Cys@MTX@RGD effectively inhibited the symptoms of RA by inhibiting the expression of pro-inflammatory cytokines (TNF-α,COX-2). We hope that the construction of nanomaterials can add potential value to the design of chemical drugs and therapeutic strategies for RA.

The single crystals of two novel copper(II)-based complexes containing L-methioninol-derived Schiff bases were obtained and characterized. The nanoparticles of these complexes were prepared and their cellular uptake was measured in MDA-MB-231 cells and HUVECs. It was found that these complexes could remarkably induce apoptosis, inhibit proliferation, suppress migration and metastasis, and inhibit angiogenesis and the growth of triple-negative breast cancer derived from MDA-MB-231 cells in vitro. Meanwhile, these complexes exhibit anticancer and antiangiogenic functions by activating the important protein molecules VEGFR2, FAK, AKT and Erk1/2 or their phosphorylated molecules p-VEGFR2, p-FAK, p-AKT, and p-Erk1/2 in the VEGF/VEGFR2 signaling pathway, collapsing the mitochondrial membrane potential, and damaging the level of reactive oxygen species.

Two mixed-ligand copper-based complexes significantly exhibit anti-cervical cancer activity by regulating the important signalling molecules downstream of the VEGF/VEGFR2 signalling pathway.

Three novel single crystals of the metal-based complexes Cu-1, Cu-2, and Co-1 were obtained and characterized. Compared with Cu-2 and Co-1, Cu-1 showed remarkable activities of anti-cervical cancer, anti-cisplatin-resistant non-small cell lung cancer and anti-angiogenesis by downregulating the expressions of important proteins in the VEGF/VEGFR2 signaling pathway to inhibit angiogenesis and cancer cell proliferation, induce apoptosis, and suppress migration and metastasis. Moreover, Cu-1 dramatically inhibited the expression of the anti-apoptotic protein Bcl-2 and up-regulated the expressions of the proapoptotic proteins caspase-9 and Bax to induce the apoptosis of tumor cells, simultaneously decreasing the density of endothelial cells to inhibit tumor angiogenesis in cisplatin-resistant tumors.

Due to the complexity and heterogeneity of solid tumors, traditional clinical treatments often only achieve limited therapeutic effects. Tumor-associated macrophages (TAMs) play a key role in the development of solid tumors, and the elimination of solid tumors based on the tumor microenvironment has proven to be an effective therapeutic strategy. Here, we successfully developed Ru-based nanoparticles, Ru@ICG–BLZ NPs, with inflammation-responsive release ability, which could repolarize TAMs into M1 macrophages (with an antitumor role) and further produce hyperthermia and ROS to eliminate cancer cells. In vitro experiments showed that Ru@ICG–BLZ NPs had superior drug (ICG and BLZ-945) loading capacity and sensitive inflammation-responsive drug release behavior, which enhanced CT26 cell uptake and penetration ability. Furthermore, in vivo experiments showed that Ru@ICG–BLZ NPs could effectively up-regulate the expression of M1 markers (iNOS, and IL-12) and exert phototherapy to ablate solid tumor, without causing obvious damage to the surrounding tissues of the tumor. The lower toxicity and excellent antitumor ability of Ru@ICG–BLZ NPs could provide new ideas for the clinical transformation of nanomedicine.