Cyclometalated Ir(III) complexes hold great promise as an alternative to platinum metallodrugs for the therapy and diagnosis of cancer. However, their low aqueous solubility and poor cell membrane permeability are obstacles for in vivo applications. Here we have encapsulated for the first time, using polyurethane–polyurea hybrid nanocapsules (NCs), two phosphorescent tris-cyclometalated Ir(III) complexes incorporating deprotonated 2-arylbenzimidazole ligands, Ir1 and Ir2. Ir(III)-Loaded nanocapsules (NC-Ir1 and NC-Ir2) showed a roughly round shape and controlled particle size distribution around 18 nm. The photophysical properties of aqueous solutions of NCs were similar to those of the free complexes in CH₂Cl₂, which accounts for the hydrophobic and protective environment generated by the nanoparticles around the cargo. Nanoencapsulation had also a positive effect on the cellular uptake of the metallodrugs and NCs were found to be highly cytotoxic towards several cancer cell lines, whereas Ir(III) complexes alone were found to be inactive. A strong tumor growth inhibition effect was also found in 3D tumorsphere cancer models owing to the high penetration capacity of small NCs. Finally, the mode of cell death of the NCs was found to be related to oncosis, and the mitochondrial dysfunction and generation of extensive oxidative stress appeared to be also involved in the mechanism of action of these novel nanomedicines.

Aortic endothelial cell dysfunction is an early trigger of atherosclerosis, the major cause of the cardiovascular disease (CVD). Nanomedicines targeting vascular endothelium and lesions hold great promise as therapeutic solutions to vascular disorders. This study investigates the vascular delivery efficacy of polyurethane-polyurea nanocapsules (Puua-NCs) with pH-synchronized shell cationization and redox-triggered release. Fluorescent lipophilic dye DiI was encapsulated into Puua-NCs of variable sizes and concentrations. In vitro cellular uptake studies with human aortic endothelial cells showed that these Puua-NCs were taken up by cells in a dose-dependent manner. In apolipoprotein E-deficient mice fed a Western diet, a model of atherosclerosis, circulating Puua-NCs were stable and accumulated in aortic endothelium and lesions within 24 hours after intravenous administration. Treatment with thiol-reducing and oxidizing reagents disrupted the disulfide bonds on the surface of internalized NCs, triggering disassembly and intracellular cargo release. Ultimately, Puua-NCs are a potential redox-controllable cardiovascular drug delivery system.

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands.

Encapsulation of water-soluble bioactive compounds for enabling specific accumulation in tumor locations, while avoiding premature clearance and/or degradation in the bloodstream, is one of the main hallmarks in nanomedicine, especially that of NIR fluorescent probes for cancer theragnosis. The herein reported technology furnishes water-dispersible double-walled polyurethane-polyurea hybrid nanocapsules (NCs) loaded with indocyanine green (ICG-NCs), using a versatile and highly efficient one-pot and industrially scalable synthetic process based on the use of two different prepolymers to set up the NCs walls. Flow cytometry and confocal microscopy confirmed that both ICG-loaded NCs internalized in monocyte-derived dendritic cells (moDCs). The in vivo analysis of xenograft A375 mouse melanoma model revealed that amphoteric functionalization of NCs’ surface promotes the selective accumulation of ICG-NCs in tumor tissues, making them promising agents for a less-invasive theragnosis of cancer.

For some time, the presence of high oxidation state Mn ions and Ca(II) in the active center of Photosystem II has been known. However, coordination complexes that combine both Mn(III) and Ca(II) have been difficult to obtain, with only a handful of examples reported. In this paper we report the synthesis of two new Mn(III)-Ca(II) complexes, 1 [Pr₂NH₂]₃[Mn₆CaO₂(OH)(OMe)₃(SALO)₆ (SALOH)₃] and 2 [Mn₁₈Ca₆O₁₂(OH)₆(MeO)₁₂(PhCOO)₁₈(MeOH)₆]. The complexes have been characterized by single-crystal X-ray diffraction to establish the oxidation state of manganese. The use of salicylato ligands with tert-butyl substituents leads to effective encapsulation of a Ca(II) ion in a cavity that has both hydrophobic and hydrophilic regions, mimicking the enzyme environment.