Pt(IV)/Re(I) Chitosan Conjugates as a Flexible Platform for the Transport of Therapeutic and/or Diagnostic Anticancer Agents

• Main Authors: Elisabetta Gabano, Letícia do Quental, Elena Perin, Francisco Silva, Paula Raposinho, António Paulo, Mauro Ravera
• Format: Article
• Language: English
• Published: MDPI AG 2017-12-01
• Series: Inorganics
• Subjects: theranostics; platinum prodrugs; rhenium complexes; chitosan; drug targeting and delivery
• Online Access: https://www.mdpi.com/2304-6740/6/1/4

New chitosan derivatives modified with (3-carboxypropyl)trimethylammonium chloride (1) and coupled with (OC-6-44)-diammine(4-carboxypropanoato)dichloridoethanolatoplatinum(IV) (2), were synthesized and their preliminary biological evaluation carried out in human tumor cells. Some of these derivatives were also loaded with a chelating ligand (3) that was derived from bis(quinolin-2-ylmethyl)amine to obtain chitosan-based nanoparticles for an EPR-mediated delivery of Pt(IV) prodrugs and Re(I) tricarbonyl complexes (4), to explore a multimodal theranostic approach to cancer. The cytotoxicity of the different chitosan conjugates (C12, C123, and C1234), carrying different combinations of the Pt(IV) complex, the chelator and the Re(I) complex, was evaluated in the A2780 human ovarian cancer cell line using the MTT assay. The Pt(IV)-containing nanosystems showed low to moderate cytotoxic activity (IC50 values in the range 13.5–33.7 µM) and was comparable to that found for the free Pt(IV) complex (IC50 = 13.7 µM). Therefore, the Pt(IV)-chitosan conjugation did not enhance the cytotoxic activity of the Pt(IV) prodrug, which certainly reflects the inefficient cellular uptake of the nanoconjugates. Nevertheless, a clearer view of their potential for the delivery of anticancer agents requires further in vivo tests because the EPR effect increases extravasation and retention within the tumor tissue, not necessarily within the tumor cells.