Solid tumors exhibit complex microenvironments that significantly hinder treatment effectiveness. Factors such as cellular heterogeneity, aberrant extracellular matrix, and specific characteristics such as hypoxia and acidic pH contribute to this challenge. This underscores the necessity for modular nanovehicles that are able to tackle multiple targets simultaneously and deliver a diverse array of therapeutic agents to the tumor.1
Silicasomes, which consist of a mesoporous silica core coated with a lipid bilayer, emerge as ideal nanocarriers for this purpose, as their unique structure allows for sophisticated customization. Their silica core can be loaded with a wide variety of chemotherapeutics, while their lipid exterior enables functionalization with additional therapeutic components. Consequently, these nanosystems can be engineered to implement a multifaceted antitumoral approach, capable of overcoming tumoral obstacles.2
In this study, a bimodular silicasome has been developed for the delivery of chemotherapeutics to solid tumors. The silica core has been used for transporting doxorubicin, while two different complementary therapeutic modules have been integrated into the lipid coating. The first type of add-on module consists of polymeric nanocapsules containing collagenase enzyme, designed to degrade the desmoplastic extracellular matrix and facilitate tumor penetration.3 For the second module, the lipid coating has been modified with beta-cyclodextrin, an oligosaccharide that enables the transportation of hydrophobic drugs, such as paclitaxel, within its interior.
Both modules have been evaluated independently against neuroblastoma. The ability of the beta-cyclodextrin to internalize tumor cells and induce drug-mediated toxicity has been assessed using flow cytometry. In contrast, the efficacy of the collagenase nanocapsules in degrading the extracellular matrix and transporting chemotherapeutics has been tested in a collagen hydrogel 3D model through the use of confocal microscopy. The results show how the supplementation of the silicasomes with these functional modules enhances the antitumoral effect of the treatment, surpassing the efficacy of lone doxorubicin delivery.
