Silica Nanobottles Filled with Photo-cross-linked GelMA for the Sustained Release of Hydrophilic Biomacromolecules

Nanobottles have garnered attention as a class of advanced carriers for drug delivery, because of their advantages, such as convenient loading, high capacity, and a well-defined wall for surface modification. However, strategies to achieve sustained release of hydrophilic biomolecules remain limited. Here, we report a hybrid delivery platform that integrates silica nanobottles with photo-cross-linked gelatin methacryloyl for the encapsulation and controlled release of proteins, enzymes, and polysaccharides. Upon cross-linking, the payloads show enhanced intracellular stability, with minimal release in A549 cells for up to 24 h. This system also enables control over release kinetics, with the half-life extendible to several weeks depending on the type and/or molecular weight of the payload. Importantly, released biomacromolecules retain structural and functional integrity, and delivery of nerve growth factor promotes robust neurite outgrowth from PC12 cells. This hybrid system provides a versatile and programmable platform for the long-term delivery of diverse hydrophilic therapeutics.