Nonporous silica nanoparticles with an external shell containing the 3‑aminopropyl arm (SiNP) were further decorated with alginic acid (SiNP-ALG) as a potential biocompatible delivery system for Pt antitumor agents. Such particles were coupled with the prodrug (OC‑6‑44)‑acetato(β‑alaninato)diamminedichloridoplatinum(IV), 1, through the formation of amide bonds between the pendant carboxylate groups on SiNP-ALG and the free amino group of the complex. Cytosol extracted from tumor cells was able to quickly and efficiently reduce the Pt(IV) prodrug, and produces the active metabolite cisplatin. SiNP-ALG-Pt conjugate was more active than both cisplatin and 1, due to its more efficient cell uptake, whereas the SiNP-ALG unplatinated nanoparticles were deprived of any nonspecific toxicity.
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