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Zeolitic imidazolate framework-8 (ZIF-8) and its composites have diverse applications. However, ZIF-8-based nanocomposites are mainly used as carriers in biomolecular delivery, with the functions of metal ions and ligands rarely used to modulate the biofunctions. In this work, dendritic mesoporous organosilica nanoparticles (DMONs) with tetrasulfide bond were used to confine ZIF-8 growth partially inside mesopores as a novel nanocomposite for mRNA delivery. Each component in the resultant DMONs-ZIF-8 contributed to mRNA delivery applications, including high loading benefitting from positively charged ZIF-8 and large mesopores of DMONs, endosomal escape promoted by the imidazole ring of ZIF-8, and long-term glutathione depletion mediated by both zinc ions and tetrasulfide bond. Combined together, DMONs-ZIF-8 demonstrated enhanced mRNA translation and better transfection efficiency than commercial products and toxic polymer-modified DMONs in vitro and in vivo., Confined growth of ZIF-8 nanocrystals in the large mesopores of organosilica nanoparticles with tetrasulfide bond is reported to upregulate mRNA translation and enhance delivery performance.

The application of nanomaterials is regarded nowadays as a highly promising approach for overcoming the limitations of the currently available cancer treatments, contributing for the creation of more effective, precise, and safer therapies. In the last years, organosilica nanoparticles arisen as alternatives to the most common mesoporous silica nanoparticles. The organosilica nanoparticles combine the advantages of the mesoporous silica, such as structural stability and mesoporous structure, with the increased biocompatibility and biodegradability of organic materials. Therefore, the variety of organic bridges that can be incorporated into the silica matrix allowed the development of new and exciting compositions, properties, and functions for improving the therapeutic effectiveness of the anticancer nanomedicines. In this review, the strategies that have been explored to create stimuli-responsive organosilica-based drug delivery systems are highlighted, describing the practical approaches and mechanisms controlling the drug release. Additionally, the organosilica nanoparticles surface modifications aimed for increasing the blood circulation time and the tumor targeting are also described.

Biodegradation is a crucial issue for silica‐based mesoporous nanoparticles that is related to the biosafety in tumor therapy. Nowadays, mesoporous silica nanoparticles (MSNs) have been intensively developed to construct multifunctional nanosystems for tumor therapy due to their biocompatibility, high drug loading capacity and easy functionalization; however, their biodegradation is relatively slow and still under debate. To improve the biodegradability of silica‐based mesoporous nanoparticles, a simple organic‐inorganic hybridization strategy to synthesize mesoporous organosilica nanoparticles (MONs) has been successfully developed. By hybridizing the silica framework (–Si–O–Si–) with stimuli‐sensitive organic moieties to form organic‐inorganic network (–Si–R–Si–, R: organic moiety), when exposed to the stimuli environment, the breakdown of the organic‐inorganic network could accelerate the degradation of MONs, which is great promising for MONs as a multifunctional therapeutic nanoplatform in tumor therapy. This review aims to summarize the degradation strategies for MONs to improve biodegradability in recent years, and highlight the potential applications of MONs in tumor therapy. Finally, we also discuss the challenges of MONs for tumor therapy in future clinical translation.