Nanoparticles have become a vital part of a vast number of established processes and products; they are used as catalysts, in cosmetics, and even by the pharmaceutical industry. Despite this, however, the reliable and reproducible production of functional nanoparticles for specific applications remains a great challenge. In this respect, reticular chemistry provides methods for connecting molecular building blocks to nanoparticles whose chemical composition, structure, porosity, and functionality can be controlled and tuned with atomic precision. Thus, reticular chemistry allows for the translation of the green chemistry principle of atom economy to functional nanomaterials, giving rise to the multifunctional efficiency concept. This principle encourages the design of highly active nanomaterials by maximizing the number of integrated functional units while minimizing the number of inactive components. State‐of‐the‐art research on reticular nanoparticles—metal‐organic frameworks, zeolitic imidazolate frameworks, and covalent organic frameworks—is critically assessed and the beneficial features and particular challenges that set reticular chemistry apart from other nanoparticle material classes are highlighted. Reviewing the power of reticular chemistry, it is suggested that the unique possibility to efficiently and straightforwardly synthesize multifunctional nanoparticles should guide the synthesis of customized nanoparticles in the future.

Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes, and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pH-responsive drug carrier system for the anticancer immune-stimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Equipped with a biotin–avidin cap, the tailor-made nanoparticles showed efficient stimuli-responsive release of their R848 cargo in an environmental pH of 5.5 or below. We showed that the MSNs loaded with R848 were rapidly taken up by APCs into the acidic environment of the lysosome and that they potently activated the immune cells. Upon subcutaneous injection into mice, the particles accumulated in migratory dendritic cells (DCs) in the draining lymph nodes, where they strongly enhanced the activation of the DCs. Furthermore, simultaneous delivery of the model antigen OVA and the adjuvant R848 by MSNs resulted in an augmented antigen-specific T-cell response. The MSNs significantly improved the pharmacokinetic profile of R848 in mice, as the half-life of the drug was increased 6-fold, and at the same time, the systemic exposure was reduced. In summary, we demonstrate that MSNs represent a promising tool for targeted delivery of the immune modulator R848 to APCs and hold considerable potential as a carrier for cancer vaccines.

Ion homeostasis is essential for cellular survival, and elevated concentrations of specific ions are used to start distinct forms of programmed cell death. However, investigating the influence of certain ions on cells in a controlled way has been hampered due to the tight regulation of ion import by cells. Here, it is shown that lipid‐coated iron‐based metal–organic framework nanoparticles are able to deliver and release high amounts of iron ions into cells. While high concentrations of iron often trigger ferroptosis, here, the released iron induces pyroptosis, a form of cell death involving the immune system. The iron release occurs only in slightly acidic extracellular environments restricting cell death to cells in acidic microenvironments and allowing for external control. The release mechanism is based on endocytosis facilitated by the lipid‐coating followed by degradation of the nanoparticle in the lysosome via cysteine‐mediated reduction, which is enhanced in slightly acidic extracellular environment. Thus, a new functionality of hybrid nanoparticles is demonstrated, which uses their nanoarchitecture to facilitate controlled ion delivery into cells. Based on the selectivity for acidic microenvironments, the described nanoparticles may also be used for immunotherapy: the nanoparticles may directly affect the primary tumor and the induced pyroptosis activates the immune system.

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In the present paper, we use zinc oxide nanoparticles under the excitation of ultraviolet (UV) light for the generation of Reactive Oxygen Species (ROS), with the aim of further using these species for fighting cancer cells in vitro. Owing to the difficulties in obtaining highly dispersed nanoparticles (NPs) in biological media, we propose their coating with a double-lipidic layer and we evaluate their colloidal stability in comparison to the pristine zinc oxide NPs. Then, using Electron Paramagnetic Resonance (EPR) coupled with the spin-trapping technique, we demonstrate and characterize the ability of bare and lipid-coated ZnO NPs to generate ROS in water only when remotely actuated via UV light irradiation. Interestingly, our results reveal that the surface chemistry of the NPs greatly influences the type of photo-generated ROS. Finally, we show that lipid-coated ZnO NPs are effectively internalized inside human epithelial carcinoma cells (HeLa) via a lysosomal pathway and that they can generate ROS inside cancer cells, leading to enhanced cell death. The results are promising for the development of ZnO-based therapeutic systems.