Shedding Light on the Cellular Uptake Mechanisms of Bioactive Glass Nanoparticles as Controlled Intracellular Delivery Platforms: A Review of the Recent Literature.

Recent advancements in nanotechnology have enabled the synthesis of bioactive glass nanoparticles (BGNs), promising multifunctional platforms for the simultaneous delivery of therapeutic ions and biomolecules. However, the intracellular efficiency of BGNs is limited by the internalization mechanism, further dictating the intracellular trafficking and fate. Following a general overview of the main uptake pathways of nanoparticles and the subsequent intracellular localization, a comprehensive analysis of the BGNs' internalization process is presented. Key findings reveal that the BGNs are mainly internalized by active transport mechanisms and are entrapped in endosomes/lysosomes, limiting their ability to exert their full intracellular therapeutic potential. Existing studies in the literature provide valuable data to correlate the uptake process with the intracellular BGN localization, but there is limited research on the fate of BGNs and the released ions once entrapped in intracellular vesicles. Therefore, in the last part, future strategies to either escape the endosome or use the lysosomal degradation as a mechanism for controlled intracellular ion release with implications for targeted modulation of cell behavior are discussed. Going beyond BGNs, this review highlights the need of understanding better the dynamically transforming degradable nanoparticles - an essential step toward achieving their full intracellular therapeutic potential.