Functional fluorescent nonporous silica nanoparticles as carriers for Pt(IV) anticancer prodrugs

• Amino-decorated SiO2 nanoparticles were used for the delivery of antitumor prodrugs.
• Mono- and di-functionalized Pt(IV) complexes derived from cisplatin were loaded.
• Only conjugates obtained from monosuccinato Pt(IV) afforded stable nanosuspensions.
• In the presence of reductants, the release of cisplatin was observed.
• Conjugates exhibited better antiproliferative activity than cisplatin and free complex.

Multilayer fluorescent nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups were used as delivery systems for Pt(IV) candidate antitumor prodrugs. Spherical SNPs of three different sizes (diameter around 120, 100, and 50 nm) were loaded with two different complexes, namely (OC-6-33)-diamminebis(4-carboxybutanoato)dichloridoplatinum(IV) (1) and (OC-6-44)-diammine(4-carboxybutanoato)dichloridoethanolatoplatinum(IV) (2), through the formation of amide bonds between the pendant amino groups on SNPs and the free carboxylic groups of the complexes. Complex 1 proved to cause heavy and irreversible agglomeration of SNPs; likely, the presence of two reactive carboxylic functionalities induces the formation of cross-links between the amino-decorated SNPs. On the contrary, the conjugates 2-SNP, obtained from the monofunctionalized 2, afforded aqueous nano-suspensions reasonably stable toward aggregation. These solutions showed a limited Pt release in water in the absence of any reducing agents, mainly in form of a Pt(IV) derivative generated by the hydrolysis of the Si–O–Si bond of the functionalized arms attached to silica. In the presence of ascorbic acid, the reduction Pt(IV) → Pt(II) caused the release of the active metabolite cisplatin. Conjugates 2-SNP exhibited much better antiproliferative activity on the Pt-sensitive ovarian A2780 cell line than parent cisplatin and free 2, due to their more efficient cellular uptake.

Multilayer fluorescent nonporous silica nanoparticles with an external shell containing primary amino groups were used as delivery systems for Pt(IV) antitumor prodrugs. Some of the conjugates exhibited much better antiproliferative activity than the parent cisplatin and the free Pt(IV) complex due to their more efficient cellular uptake.Figure optionsDownload as PowerPoint slide