The aim of this original review is to highlight and analyze the most recent progress and challenges in the synthesis and surface modifications of superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) for multimodal imaging and therapy applications, which represent important fields in medicine in general and cancer in particular. Thus, the oncology domain is rapidly moving to a more personalized medicine including precision imaging and theranostic approaches. Novel biocompatible Fe₃O₄ nanoparticulate systems have been designed for enhanced and targeted cellular uptake by surface layer coating modifications, to have improved r₂ relaxivity for sensitive magnetic resonance (MR) imaging applications, to have the ability to be used for dual mode imaging, and to be used for imaging-guided cancer therapy. In this review, we analyzed in depth the new strategies for generating biocompatible multifunctional Fe₃O₄ nanoplatforms for both the diagnosis and therapy of cancer.

Overview of the use of dendrimers in combination with encapsulated and conjugated natural products and analogues as anti-cancer agents.

RS67333 is a partial serotonin subtype 4 receptor (5-HT₄R) agonist that has been widely studied for its procognitive effect. More recently, it has been shown that its ability to promote the nonamyloidogenic cleavage of the precursor of the neurotoxic amyloid-β peptide leads to the secretion of the neurotrophic protein sAPPα. This effect has generated great interest in RS67333 as a potential treatment for Alzheimer’s disease (AD). We show herein that RS67333 is also a submicromolar acetylcholinesterase (AChE) inhibitor and therefore, could contribute, through this effect, to the restoration of the cholinergic neurotransmission that becomes altered in AD. We planned to pharmacomodulate RS67333 to enhance its AChE inhibitory activity to take advantage of this pleiotropic pharmacological profile in the design of a novel multitarget-directed ligand that is able to exert not only a symptomatic but also, a disease-modifying effect against AD. These efforts allowed us to select donecopride as a valuable dual (h)5-HT₄R partial agonist (K_i = 10.4 nM; 48.3% of control agonist response)/(h)AChEI (IC₅₀ = 16 nM) that further promotes sAPPα release (EC₅₀ = 11.3 nM). Donecopride, as a druggable lead, was assessed for its in vivo procognitive effects (0.1, 0.3, 1, and 3 mg/kg) with an improvement of memory performances observed at 0.3 and 1 mg/kg on the object recognition test. On the basis of these in vitro and in vivo activities, donecopride seems to be a promising drug candidate for AD treatment.

Ultrasmall Fe₃O₄ nanoparticles can be functionalized with an RGD peptide via a PEG spacer for targeted T₁-weighted MR imaging of tumors.