Core–shell nanoparticles as prodrugs: Possible cytotoxicological and biomedical impacts of batch-to-batch inconsistencies

Numerous samples of magnetite@silica and magnetite@silica@silane core–shell nanoparticles, previously used as prodrugs, were prepared by an experienced chemist, using the same identical equipment and the same lots of reagents. Their surface analyses showed batch-to-batch chemical variations: no two batches were found to have the same surface chemistries, showing unexpected Si–O bond scission and amine oxidation. Because the preparations used reactions recognized to be mild, and bond scission and oxidation were never previously reported for similar reactions on larger surfaces, the Fe3O4 nanoparticles that form the nanoparticle core appear to have acted as catalysts for these side reactions. The intended use of these nanoparticles, as drug carriers, is discussed in terms of cytotoxicological and biomedical consequences.

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► Magnetite@silica@silane NPs were formed and functionalized in solution.
► Surface analysis showed unexpected side-reactions.
► Side-reactions included bond fragmentation and oxidation.
► Batch-to-batch inconsistencies included number and extent of side-reactions.
► Implications for use in drug delivery, and associated toxicity, are discussed.