Gadolinium and Platinum in Tandem: Real-time Multi-Modal Monitoring of Drug Delivery by MRI and Fluorescence Imaging

Abstract

A novel dual-imaging cisplatin-carrying molecular cargo capable of performing simultaneous optical and MR imaging is reported herein. This long-lasting MRI contrast agent (r1 relaxivity of 23.4 mM-1s-1 at 3T, 25 oC) is a photo-activated cisplatin prodrug (PtGdL) which enables real-time monitoring of anti-cancer efficacy. PtGdL is a model for monitoring the drug delivery and anti-cancer efficacy by MRI with a much longer retention time (24 hours) in several organs such as renal cortex and spleen than GdDOTA and its motif control GdL. Upon complete release of cisplatin, all PtGdL is converted to GdL enabling subsequent MRI analyses of therapy efficacy within its reasonably short clearance time of 4 hours. There is also responsive fluorescence enhancement for monitoring by photon-excitation.

Cancer cell targeting, controlled drug release and intracellular fate of biomimetic membrane-encapsulated drug-loaded nano-graphene oxide nanohybrids

“…The dose for the last two groups is 5 mg equivalent DOX per kg animal. The tumor volumes were measured every 2 days for 14 days and then calculated with volume = 1/2 (LW) 2 , where L was the maximum diameter and W was the minimum diameter of a tumor. Body weights and survival curves were also recorded after the treatments.…”

“…Driven by the most updated development of materials chemistry 1, 2 and analytical sciences 3 , nanoparticles-based drug delivery systems (DDSs) have been utilized in preclinical and clinical cancer therapy. They can improve therapeutic effects while decreasing side effects of anticancer drugs.…”

Current Trends in Cancer Nanotheranostics: Metallic, Polymeric, and Lipid-Based Systems

“…For instance, Kostevsek et al (2015) developed a one-step formulation of gold–iron oxide nanoparticles functionalized with chitosan, as a biocompatible polymeric shell, which combined both photothermal heating properties and photoacoustic imaging (PAI) with a contrast agent [12]. Another study focused on the development of a dual-imaging theranostic prodrug system, capable of producing a photo-controlled release of cisplatin and performing simultaneously optical and MRI-based guidance [13]. At a first approach, this gadolinium–platinum complex allowed a real-time assessment of the biodistribution and pharmacokinetics of the anticancer treatment, in addition to an increased retention at the tumor site compared to free cisplatin [13].…”

“…Another study focused on the development of a dual-imaging theranostic prodrug system, capable of producing a photo-controlled release of cisplatin and performing simultaneously optical and MRI-based guidance [13]. At a first approach, this gadolinium–platinum complex allowed a real-time assessment of the biodistribution and pharmacokinetics of the anticancer treatment, in addition to an increased retention at the tumor site compared to free cisplatin [13]. Willerding et al (2016) developed long-circulating thermosensitive liposomes (TSLs) co-encapsulating doxorubicin and a gadolinium-based contrast agent.…”

Bladder Cancer Photodynamic Therapeutic Agent with Off‐On Magnetic Resonance Imaging Enhancement

“…The term “theranostic” characterizes a class of multifunctional compounds with both therapeutic and diagnostic functions. In particular, the combination of PDT with magnetic resonance imaging (MRI) seems to have promising potential, especially for those working under two‐photon excitation . With bi‐functional drugs attracting more attention, the balance between the doses for either purpose, however, becomes a concern, because of Gd(III)‐based theranostic agents usually having a higher dose requirement for imaging than the toxic dose for drug molecules.…”