Abstract: There are many nanoencapsulation systems available today. Among all these, mesoporous silica particles (MSPs) have received great attention in the last few years. Their large surface-to-volume ratio, biocompatibility, and versatility allow the encapsulation of a wide variety of drugs inside their pores. However, their chemical instability in biological fluids is a handicap to program the precise release of the therapeutic compounds. Taking advantage of the dissolving capacity of silica, in this study, we generate hollow capsules using MSPs as transitory sacrificial templates. We show how, upon MSP coating with different polyelectrolytes or proteins, fully customized hollow shells can be produced. These capsules are biocompatible, flexible, and biodegradable, and can be decorated with nanoparticles or carbon nanotubes to endow the systems with supplementary intrinsic properties. We also fill the capsules with a fluorescent dye to demonstrate intracellular compound release. Finally, we document how fluorescent polymeric capsules are engulfed by cells, releasing their encapsulated agent during the first 96 h. In summary, here, we describe how to assemble a highly versatile encapsulation structure based on silica mesoporous cores that are completely removed from the final polymeric capsule system. These drug encapsulation systems are highly customizable and have great versatility as they can be made using silica cores of different sizes and multiple coatings. This provides capsules with unique programmable attributes that are fully customizable according to the specific needs of each disease or target tissue for the development of nanocarriers in personalized medicine.

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