Mesoporous silica nanoparticles (MSNs) have attracted the attention of chemists, who have developed numerous systems for the encapsulation of a plethora of molecules, allowing the use of mesoporous silica nanoparticles for biomedical applications. MSNs have been extensively studied for their use in nanomedicine, in applications such as drug delivery, diagnosis, and bioimaging, demonstrating significant in vivo efficacy in different preclinical models. Nevertheless, for the transition of MSNs into clinical trials, it is imperative to understand the characteristics that make MSNs effective and safe. The biosafety properties of MSNs in vivo are greatly influenced by their physicochemical characteristics such as particle shape, size, surface modification, and silica framework. In this review, we compile the most relevant and recent progress in the literature up to the present by analyzing the contributions on biodistribution, biodegradability, and clearance of MSNs. Furthermore, the ongoing clinical trials and the potential challenges related to the administration of silica materials for advanced therapeutics are discussed. This approach aims to provide a solid overview of the state-of-the-art in this field and to encourage the translation of MSNs to the clinic.

Cancer immunotherapy has emerged in the past decade as a promising strategy for treating many forms of cancer by stimulating the patient's immune system. Although immunotherapy has achieved some promising results in clinics, more efforts are required to improve the limitations of current treatments related to lack of effective and targeted cancer antigens delivery to immune cells, dose‐limiting toxicity, and immune‐mediated adverse effects, among others. In recent years, the use of nanomaterials has proven promising to enhance cancer immunotherapy efficacy and reduce side effects. Among nanomaterials, attention has been recently paid to mesoporous silica nanoparticles (MSNs) as a potential multiplatform for enhancing cancer immunotherapy by considering their unique properties, such as high porosity, and good biocompatibility, facile surface modification, and self‐adjuvanticity. This review explores the role of MSN and other nano/micro‐materials as an emerging tool to enhance cancer immunotherapy, and it comprehensively summarizes the different immunotherapeutic strategies addressed to date by using MSN.

ConspectusCellular senescence can be defined as an irreversible stopping of cell proliferation that arises in response to various stress signals. Cellular senescence is involved in diverse physiological and pathological processes in different tissues, exerting effects on processes as differentiated as embryogenesis, tissue repair and remodeling, cancer, aging, and tissue fibrosis. In addition, the development of some pathologies, aging, cancer, and other age-related diseases has been related to senescent cell accumulation. Due to the complexity of the senescence phenotype, targeting senescent cells is not trivial, is challenging, and is especially relevant for in vivo detection in age-related diseases and tissue samples. Despite the elimination of senescent cells (senolysis) using specific drugs (senolytics) that have been shown to be effective in numerous preclinical disease models, the clinical translation is still limited due to the off-target effects of current senolytics and associated toxicities. Therefore, the development of new chemical strategies aimed at detecting and eliminating senescent cells for the prevention and selective treatment of senescence-associated diseases is of great interest. Such strategies not only will contribute to a deeper understanding of this rapidly evolving field but also will delineate and inspire new possibilities for future research.In this Account, we report our recent research in the development of new chemical approaches for the detection and elimination of senescent cells based on new probes, nanoparticles, and prodrugs. The designed systems take advantage of the over-representation in senescent cells of certain biomarkers such as β-galactosidase and lipofuscin. One- and two-photon probes, for higher tissue penetration, have been developed. Moreover, we also present a renal clearable fluorogenic probe for the in vivo detection of the β-galactosidase activity, allowing for correlation with the senescent burden in living animals. Moreover, as an alternative to molecular-based probes, we also developed nanoparticles for senescence detection. Besides, we describe advances in new therapeutic agents to selectively eradicate senescent cells using β-galactosidase activity-sensitive gated nanoparticles loaded with cytotoxic or senolytic agents or new prodrugs aiming to increase the selectivity and reduction of off-target toxicities of current drugs. Moreover, new advances therapies have been applied in vitro and in vivo. Studies with the probes, nanoparticles, and prodrugs have been applied in several in vitro and in vivo models of cancer, fibrosis, aging, and drug-induced cardiotoxicity in which senescence plays an important role. We discuss the benefits of these chemical strategies toward the development of more specific and sophisticated probes, nanoparticles, and prodrugs targeting senescent cells.

Bioinspired nano/micromotors with drug delivery capabilities are emerging tools with the promising potential to treat numerous diseases. However, some major challenges must be overcome before reaching real biomedical applications. Above all, it is necessary to design engines that employ biocompatible and bioavailable fuels to induce efficient propulsion in biological environments. In addition, ideal nanomotors should also be capable of delivering the cargo on-command using selected stimuli. To tackle these challenges, we herein present the design and evaluation (both in vitro and in vivo) of a glucose-driven gated Janus nanomotor that performs on-demand anticancer drug delivery to treat solid tumors. The motor's nanoarchitectonics is based on the anisotropic conjunction of catalytic platinum nanodendrites (PtNds) and a mesoporous silica nanoparticle (acting as a nanocontainer for anticancer drug doxorubicin) capped with enzyme glucose oxidase (GOx). Autonomous nanomotor movement is achieved thanks to two catalytic components, GOx and PtNds, in a hybrid cascade reaction: GOx transforms glucose to give H₂O₂ that is subsequently catalyzed by PtNds into H₂O and O₂. Besides, gatekeeper moieties (GOx) respond to the presence of intracellular proteases, which induces doxorubicin delivery. Biological experiments with the nanomotor are carried out in cancer cell cultures, three-dimensional (3D) tumor models (spheroids), in vivo and in patient-derived organoids (PDOs). A strong anticancer effect is found and attributed to the synergistic combination glucose-induced propulsion, controlled drug delivery, elimination of glucose (by GOx), ROS production (H₂O₂ generation by GOx) and hypoxia reduction (O₂ generated by PtNds). Taken together, this study advances the engineering of endogenously fueled nanomotors for in vivo operation and provides insights into the application of active particles in cancer therapy toward clinical application.