Compatibility of Nucleobases Containing Pt(II) Complexes with Red Blood Cells for Possible Drug Delivery Applications.

The therapeutic advantages of some platinum complexes as major anticancer chemotherapeutic agents and of nucleoside analogue-based compounds as essential antiviral/antitumor drugs are widely recognized. Red blood cells (RBCs) offer a potential new strategy for the targeted release of therapeutic agents due to their biocompatibility, which can protect loaded drugs from inactivation in the blood, thus improving biodistribution. In this study, we evaluated the feasibility of loading model nucleobase-containing Pt(II) complexes into human RBCs that were highly stabilized by four N-donors and susceptible to further modification for possible antitumor/antiviral applications. Specifically, platinum-based nucleoside derivatives [PtII(dien)(N7-Guo)]2+, [PtII(dien)(N7-dGuo)]2+, and [PtII(dien)(N7-dGTP)] (dien = diethylenetriamine; Guo = guanosine; dGuo = 2'-deoxy-guanosine; dGTP = 5'-(2'-deoxy)-guanosine-triphosphate) were investigated. These Pt(II) complexes were demonstrated to be stable species suitable for incorporation into RBCs. This result opens avenues for the possible incorporation of other metalated nucleobases analogues, with potential antitumor and/or antiviral activity, into RBCs.

Optimization of magnetic nanoparticles for engineering erythrocytes as theranostic agents.

The application of superparamagnetic iron oxide nanoparticles (SPIONs) in drug delivery, magnetic resonance imaging, cell tracking, and hyperthermia has been long exploited regarding their inducible magnetic properties. Nevertheless, SPIONs remain rapidly cleared from the circulation by the reticuloendothelial system (RES) or mononuclear phagocyte system, with uptake dependent on several factors such as the hydrodynamic diameter, electrical charge and surface coating. This rapid clearance of SPION-based theranostic agents from circulation is one of the main challenges hampering the medical applications that differ from RES targeting. This work proposes a strategy to render biocompatible SPIONs through their encapsulation in the red blood cells (RBCs). In this work, the research has been focused on the multi-step optimization of chemical synthesis of magnetic nanoparticles (MNPs), precisely iron oxide nanoparticles (IONPs) and zinc manganese-ferrite nanoparticles (Zn/Mn FNPs), for encapsulation in human and murine RBCs. The encapsulation through the transient opening of RBC membrane pores requires extensive efforts to deliver high-quality nanoparticles in terms of chemical properties, morphology, stability and biocompatibility. After reaching this goal, in vitro experiments were performed with selected nanomaterials to investigate the potential of engineered MNP-RBC constructs in theranostic approaches.