Nanoparticle science is rapidly changing the landscape of various scientific fields and defining new technological platforms. This is perhaps even more evident in the field of nanomedicine whereby nanoparticles have been used as a tool for the treatment and diagnosis of many diseases. However, despite the tremendous benefit conferred, common pitfalls of this technology is its potential short and long-term effects on the human body. To understand these issues, many scientific studies have been carried out. This review attempts to shed light on some of these studies and its outcomes. The topics that were examined in this review include the different possible uptake pathways of nanoparticles and intracellular trafficking routes. Additionally, the effect of physicochemical properties of nanoparticle such as size, shape, charge and surface chemistry in determining the mechanism of uptake and biological function of nanoparticles are also addressed.

A highly stable and magnetized citric acid (CA)-functionalized iron oxide aqueous colloidal solution (Fe₃O₄@CA) was synthesized by using a simple and rapid method of one-step co-participation via a chemical reaction between Fe³⁺ and Fe²⁺ in a NaOH solution at 65 °C, followed by CA addition to functionalize the Fe₃O₄ surface in 25 min. The NPs were synthesized at lower temperatures and shortened time compared with conventional methods. Surface functionalization is highly suggested because bare Fe₃O₄ nanoparticles (Fe₃O₄ NPs) are frequently deficient due to their low stability and hydrophilicity. Hence, 19 nm-sized Fe₃O₄ NPs coated with CA (Fe₃O₄@CA) were synthesized, and their microstructure, morphology, and magnetic properties were characterized using X-ray diffraction, transmission electron microscopy, Zeta potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometer. CA successfully modified the Fe₃O₄ surface to obtain a stabilized (homogeneous and well dispersed) aqueous colloidal solution. The Zeta potential value of the as-prepared Fe₃O₄@CA increases from − 31 to − 45 mV. These CA-functionalized NPs with high magnetic saturation (54.8 emu/g) show promising biomedical applications.

Protein corona has became a prevalent subject in the field of nanomedicine owing to its diverse role in determining the efficiency, efficacy, and the ultimate biological fate of the nanomaterials used as a tool to treat and diagnose various diseases. For instance, protein corona formation on the surface of nanoparticles can modify its physicochemical properties and interfere with its intended functionalities in the biological microenvironments. As such, much emphasis should be placed in understanding these complex phenomena that occur at the bio-nano interface. The main aim of this review is to present different factors that are influencing protein-nanoparticle interaction such as physicochemical properties of nanoparticle (i.e., size and size distribution, shape, composition, surface chemistry, and coatings) and the effect of biological microenvironments. Apart from that, the effect of ignored factors at the bio-nano interface such as temperature, plasma concentration, plasma gradient effect, administration route, and cell observer were also addressed.