Unicellular diatom microalgae are a promising natural resource of porous biosilica. These microorganisms produce around their membrane a highly porous and extremely structured silica shell called frustule. Once harvested from living algae or from fossil sediments of diatomaceous earth, this biocompatible and non-toxic material offers an exceptional potential in the field of micro/nano-devices, drug delivery, theranostics, and other medical applications. The present review focused on the use of diatoms in the field of drug delivery systems, with the aim of presenting the different strategies implemented to improve the biophysical properties of this biosilica in terms of drug loading and release efficiency, targeted delivery, or site-specific binding capacity by surface functionalization. The development of composite materials involving diatoms for drug delivery applications is also described.

Bio-inspired drug capsules: The synthesis of a new vitamin-B₁₂modified biomaterial with increased static adherence properties toward cancer cell lines, allowed the targeted delivery of a poorly water-soluble ruthenium drug with an unprecedented release profile.

Systemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and characterization of a bio-inspired hybrid multifunctional drug delivery system based on diatom microalgae. The microalgae’s surface was chemically functionalized with hybrid vitamin B₁₂-photoactivatable molecules and the materials further loaded with highly active rhenium(I) tricarbonyl anticancer complexes. The constructs showed enhanced adherence to colorectal cancer (CRC) cells and slow release of the chemotherapeutic drugs. The overall toxicity of the hybrid multifunctional drug delivery system was further enhanced by photoactivation of the microalgae surface. Depending on the construct and anticancer drug, a 2-fold increase in the cytotoxic efficacy of the drug was observed upon light irradiation. The use of this targeted drug delivery strategy, together with selective spatial–temporal light activation, may lead to lower effective concentration of anticancer drugs, thereby reducing medication doses, possible side effects and overall burden for the patient.

A series of tricarbonyl manganese complexes bearing 4-ethynyl-2,2'-bipyridine and 5-ethynyl-1,10-phenanthroline α-diimine ligands were synthetized, characterized and conjugated to vitamin B12, previously used as a vector for drug delivery, to take advantage of its water solubility and specificity toward cancer cells. The compounds act as photoactivatable carbon monoxide-releasing molecules rapidly liberating on average ca. 2.3 equivalents of CO upon photo-irradiation. Complexes and conjugates were tested for their anticancer effects, both in the dark and following photo-activation, against breast cancer MCF-7, lung carcinoma A549 and colon adenocarcinoma HT29 cell lines as well as immortalized human bronchial epithelial cells 16HBE14o- as the non-carcinogenic control. Our results indicate that the light-induced cytotoxicity these molecules can be attributed to both their released CO and to their CO-depleted metal fragments including liberated ligands.