One of the major challenges in medicine is the delivery and control of drug release over time. Current approaches take advantage of mesostructured silica nanoparticles (MSNs) as carriers but suffer several problems including complex synthesis that requires sequential steps for (1) removal of surfactants and (2) functionalization of MSNs to allow upload of the drugs. Here, a novel solution is presented to these restrictions: the design of drug-structure-directing agents (DSDAs) with dual inherent pharmacological activity and ability to direct the formation of solid and hollow-shell MSNs. Pharmacologically active DSDAs obtained by amidation of drugs with fatty acids are allowed to form micelles, around which the inorganic species self-assembled to form MSNs. Since the DSDAs direct the formation of MSNs, the steps to remove surfactants, functionalization, and drug upload are not required. The MSNs thus prepared provide sustained release of the drug over more than six months, as well as rapid cellular internalization by both physiological and tumoral human colon cells without affecting cell viability. Moreover, the gradual intracellular release of both, the active drug and lipid moiety with potential nutraceutical properties is proved. MSN particles designed with this approach are promising vehicles for controlled and sustained intra-or extracellular drug-delivery.