Antitumor properties of platinum(iv) prodrug-loaded silk fibroin nanoparticles.

Platinum(iv) complexes take advantage of the exclusive conditions that occur within the tumor to carry out their cytotoxic activity. On the other hand, silk fibroin has natural properties which make it very interesting as a biomaterial: high biocompatibility, biodegradability, low immunogenicity, high cellular penetration capacity and high reactive surface. Herein we report the preparation of silk fibroin nanoparticles (SFNs) loaded with the hydrophobic Pt(iv) complex cis,cis,trans-[Pt(NH(3))(2)Cl(2)(O(2)CC(6)H(5))(2)] (PtBz). Only a small fraction of the loaded PtBz is released (less than 10% after 48 h). PtBz-SFNs trigger strong cytotoxic effects against human ovarian carcinoma A2780 cells and their cisplatin-resistant variant A2780cisR cells. Interestingly, PtBz-SFNs are very cytotoxic (nanomolar IC(50) values) toward the triple negative breast tumor cell line MDA-MB-231, and also toward SK-BR-3 and MCF-7, while maintaining an excellent selectivity index.

Anticancer C,N-cycloplatinated(II) complexes containing fluorinated phosphine ligands: synthesis, structural characterization, and biological activity.

A series of potent C,N-cycloplatinated(II) phosphine antitumor complexes containing fluorous substituents in the cyclometalated or the ancillary phosphine ligands [Pt(C-N)(PR3)Cl] or both have been synthesized and characterized. The crystal structure of [Pt(dmba){P(C6H4CF3-p)3}Cl]·2CH2Cl2 (dmba = dimethylaminomethyl)phenyl) has been established by X-ray diffraction. Values of IC50 of the new platinum complexes were calculated toward a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). Complexes containing P(C6H4CF3-p)3 as ancillary ligand (with a bulky and electronegative CF3 substituent in para position) were the most cytotoxic compounds in all the tested cancer cell lines. In some cases, the IC50 values were 16-fold smaller than that of cisplatin and 11-fold smaller than the non-fluorous analogue [Pt(dmba)(PPh3)Cl]. On the other hand, very low resistance factors (RF) in A2780cisR (cisplatin-resistant ovarian carcinoma) at 48 h were observed (RF ≈ 1) for most of the new compounds. Analysis of cell cycle was done for the three more active compounds in A2780. They arrest cell growth in G0/G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. They are also good cathepsin B inhibitors (an enzyme implicated in a number of cancer related events).