DBCO-(PEG2-Val-Cit-PAB)2

Compound [H(2)dbco](2) x [Cl(3)] x [CuCl(3)(H(2)O)(2)] x H(2)O undergoes a sharp dielectric anomaly and a paraelectric-to-ferroelectric phase transition at approximately -23 degrees C with a spontaneous polarization of 1.04 microC cm(-2), being the first molecular metal coordination compound ferroelectrics with a large dielectric response involving a 2 orders of magnitude enhancement and distinct Curie phase transition point. This work has proved an effective way for exploration of new ferroelectrics based on a five-coordinated divalent metal through the combination of crystal engineering and Landau phase transition theory.

Background:Tumor-derived exosomes (TEX) have shown great potential for drug delivery and tumor targeting. Here, we developed a novel multi-drug loaded exosomes nanoprobe for combined antitumor chemotherapy and photodynamic therapy, and monitoring the drug delivery capabilities with pre-targeting technique.

Liver cancer cells evade immune surveillance and anticancer response through various pathways, including the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) immune checkpoint axis that exhausts CD8+ T cells. Inhibitors or antibodies of the PD-L1/PD-1 signaling axis are considered promising drugs for cancer immunotherapy and exhibit favorable clinical responses. However, adverse effects, immune tolerance, and delivery barriers of most patients limit the clinical application of PD-L1/PD-1 antibodies. Thus, it is critical to develop a novel delivery strategy to enhance anticancer immunotherapy. In this study, we bioengineered cell membrane-derived nanovesicles (NVs) presenting PD-1 proteins and dibenzocyclooctyne (DBCO) to encapsulate 1-methyltryptophan (1-MT) (DBCO+PD-1@1-MT NVs). DBCO can specifically interact with N-azidoacetylmannosamine-tetraacetylate (Ac4ManN3) labeled onto metabolic cells for targeted killing of cancers. We next explored the effects of DBCO+PD-1@1-MT NVs on anticancer Hepa1-6 cells in vitro and in vivo. Results showed that PD-1@1-MT NVs dramatically inhibited Hepa1-6 proliferation, promoted peripheral blood mononuclear cell (PBMC) expansion, and strengthened anticancer therapy via blockading the PD-1/PD-L1 immune checkpoint axis, owing to the 1-methyltryptophan (1-MT) enhancement of anticancer immunotherapy efficacy through suppressing the activity of indoleamine 2,3-dioxygenase (IDO). Thus, 1-MT was encapsulated into PD-1 NVs to synergistically enhance cancer immunotherapy. Results have shown that PD-1@1-MT NVs obviously attenuated tumor growth, promoting IFN-γ production, increasing the T cells infiltration in tumors and spleens, and improving the survival period of tumor-bearing mice compared to monotherapy. Therefore, we propose a promising delivery strategy of the combination of DBCO+PD-1 NVs and 1-MT for specific and effective cancer-targeted immunotherapy.