TY - JOUR
T1 - Functional fluorescent nonporous silica nanoparticles as carriers for Pt(IV) anticancer prodrugs
AU - Ravera, Mauro
AU - Perin, Elena
AU - Gabano, Elisabetta
AU - Zanellato, Ilaria
AU - Panzarasa, Guido
AU - Sparnacci, Katia
AU - Laus, Michele
AU - Osella, Domenico
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
KW - Antiproliferative activity
KW - Drug delivery
KW - Enhanced permeability and retention effect
KW - Nonporous silica nanoparticles
KW - Pt(IV) prodrug
UR - http://www.scopus.com/inward/record.url?scp=84949627787&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2015.08.001
DO - 10.1016/j.jinorgbio.2015.08.001
M3 - Article
SN - 0162-0134
VL - 151
SP - 132
EP - 142
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
ER -