Iron oxide nanoparticles are one of the most versatile and safe nanomaterials used in medicine. Recent progress in nanochemistry enables fine control of the size, crystallinity, uniformity, and ...surface properties of iron oxide nanoparticles. In this review, the synthesis of chemically designed biocompatible iron oxide nanoparticles with improved quality and reduced toxicity is discussed for use in diverse biomedical applications.
High‐quality iron oxide nanoparticles, synthesized on a large scale via green chemistry and a chemically well‐designed biocompatible shell, have great potential as a new iron‐oxide‐based nanomedicine.
Magnetic iron oxide nanoparticles have been extensively investigated for their various biomedical applications including diagnostic imaging, biological sensing, drug, cell, and gene delivery, and ...cell tracking. Recent advances in the designed synthesis and assembly of uniformly sized iron oxide nanoparticles have brought innovation in the field of nanomedicine. This Account provides a review on the recent progresses in the controlled synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications. In particular, it focuses on three topics: stringent control of particle size during synthesis via the “heat-up” process, surface modification for the high stability and biocompatibility of the nanoparticles for diagnostic purposes, and assembly of the nanoparticles within polymers or mesoporous silica matrices for theranostic applications. Using extremely small 3 nm sized iron oxide nanoparticles (ESION), a new nontoxic T1 MRI contrast agent was realized for high-resolution MRI of blood vessels down to 0.2 mm. Ferrimagnetic iron oxide nanoparticles (FION) that are larger than 20 nm exhibit extremely large magnetization and coercivity values. The cells labeled with FIONs showed very high T2 contrast effect so that even a single cell can be readily imaged. Designed assembly of iron oxide nanoparticles with mesoporous silica and polymers was conducted to fabricate multifunctional nanoparticles for theranostic applications. Mesoporous silica nanoparticles are excellent scaffolds for iron oxide nanoparticles, providing magnetic resonance and fluorescence imaging modalities as well as the functionality of the drug delivery vehicle. Polymeric ligands could be designed to respond to various biological stimuli such as pH, temperature, and enzymatic activity. For example, we fabricated tumor pH-sensitive magnetic nanogrenades (termed PMNs) composed of self-assembled iron oxide nanoparticles and pH-responsive ligands. They were utilized to visualize small tumors (<3 mm) via pH-responsive T1 MRI and fluorescence imaging. Also, superior photodynamic therapeutic efficacy in highly drug-resistant heterogeneous tumors was observed. We expect that these multifunctional and bioresponsive nanoplatforms based on uniformly sized iron oxide nanoparticles will provide more unique theranostic approaches in clinical uses.
Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by ...reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H
that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients.
The use of iron oxide-based nanoparticles in magnetoresponsive therapy and multimodal imaging is examined. Topics discussed include magnetic nanoparticles as a delivery platform, magnetic ...nanoparticles as a therapeutic platform and the biosafety of magnetic nanoparticles.
Designed synthesis and assembly of nanoparticles assisted by their surface ligands can create “smart” materials with programmed responses to external stimuli for biomedical applications. These ...assemblies can be designed to respond either exogenously (for example, to magnetic field, temperature, ultrasound, light, or electric pulses) or endogenously (to pH, enzymatic activity, or redox gradients) and play an increasingly important role in a diverse range of biomedical applications, such as biosensors, drug delivery, molecular imaging, and novel theranostic systems. In this review, the recent advances and challenges in the development of stimuli‐responsive nanoparticle assemblies are summarized; in particular, the application‐driven design of surface ligands for stimuli‐responsive nanoparticle assemblies that are capable of sensing small changes in the disease microenvironment, which induce the related changes in their physico‐chemical properties, is described. Finally, possible future research directions and problems that have to be addressed are briefly discussed.
Dynamic nanoparticle assembly can create “smart” materials with programmed responses to external stimuli for biomedical applications. The recent advances and challenges in the development of stimuli‐responsive nanoparticle assemblies are shown, along with their diverse range of biomedical applications, such as biosensors, drug delivery, molecular imaging, and novel theranostic systems.
Histopathological level imaging in a non-invasive manner is important for clinical diagnosis, which has been a tremendous challenge for current imaging modalities. Recent development of ...ultra-high-field (UHF) magnetic resonance imaging (MRI) represents a large step toward this goal. Nevertheless, there is a lack of proper contrast agents that can provide superior imaging sensitivity at UHF for disease detection, because conventional contrast agents generally induce T2 decaying effects that are too strong and thus limit the imaging performance. Herein, by rationally engineering the size, spin alignment, and magnetic moment of the nanoparticles, we develop an UHF MRI-tailored ultra-sensitive antiferromagnetic nanoparticle probe (AFNP), which possesses exceptionally small magnetisation to minimize T2 decaying effect. Under the applied magnetic field of 9 T with mice dedicated hardware, the nanoprobe exhibits the ultralow r
/r
value (~1.93), enabling the sensitive detection of microscopic primary tumours (<0.60 mm) and micrometastases (down to 0.20 mm) in mice. The sensitivity and accuracy of AFNP-enhanced UHF MRI are comparable to those of the histopathological examination, enabling the development of non-invasive visualization of previously undetectable biological entities critical to medical diagnosis and therapy.
Restoration of tissue integrity and tissue function of wounded skin are both essential for wound repair and regeneration, while synergistic promotion of the two remains elusive. Since elevated ...reactive oxygen species (ROS) production in the injured site has been implicated in triggering a set of deleterious effects such as cellular senescence, fibrotic scarring, and inflammation, it is speculated that alleviating oxidative stress in the microenvironment of injured site would be beneficial to promote regenerative wound healing. In this study, a highly versatile ROS-scavenging tissue adhesive nanocomposite is synthesized by immobilizing ultrasmall ceria nanocrystals onto the surface of uniform mesoporous silica nanoparticles (MSN). The ceria nanocrystals decorated MSN (MSN-Ceria) not only has strong tissue adhesion strength, but also significantly restricts ROS exacerbation mediated deleterious effects, which efficiently accelerates the wound healing process, and more importantly, the wound area exhibits an unexpected regenerative healing characteristic featured by marked skin appendage morphogenesis and limited scar formation. This strategy can also be adapted to other wound repair where both ROS-scavenging activity and tissue adhesive ability matter.
Regenerative Wound Healing! Efficient restoration of tissue integrity and function are achieved by using a ROS-scavenging tissue adhesive MSN-Ceria. The synergistic effect between nanobridging effect for restoration of tissue integrity and ROS scavenging for oxidative stress modulating enable not only accelerated wound healing process but also an unexpected regenerative healing. Display omitted
Impaired diabetic wound healing represents a devastating and rapidly growing clinical problem associated with high morbidity, mortality, and recurrence rates. Engineering therapeutic angiogenesis in ...the wounded tissue is critical for successful wound healing. However, stimulating functional angiogenesis of the diabetic wound remains a great challenge, due to the oxidative damage and denaturation of bio-macromolecule-based angiogenic agents in the oxidative diabetic wound microenvironment. Here, we present a unique “seed-and-soil” strategy that circumvents the limitation by simultaneously reshaping the oxidative wound microenvironment into a proregenerative one (the “soil”) and providing proangiogenic miRNA cues (the “seed”) using an miRNA-impregnated, redox-modulatory ceria nanozyme-reinforced self-protecting hydrogel (PCN-miR/Col). The PCN-miR/Col not only reshapes the hostile oxidative wound microenvironment, but also ensures the structural integrity of the encapsulated proangiogenic miRNA in the oxidative microenvironment. Diabetic wounds treated with the PCN-miR/Col demonstrate a remarkably accelerated wound closure and enhanced quality of the healed wound as featured by highly ordered alignment of collagen fiber, skin appendage morphogenesis, functional new blood vessel growth, and oxygen saturation.
Iron oxide nanoparticle (IONP)-based magnetic resonance imaging (MRI) contrast agents have been widely used for the diagnosis of hepatic lesions. However, current IONP-based liver-specific MRI ...contrast agents rely on single-phase contrast enhancement of the normal liver, which is not sensitive enough to detect early stage small hepatocellular carcinomas (HCCs). We herein report i-motif DNA-assisted pH-responsive iron oxide nanocluster assemblies (termed RIAs), which provide an inverse contrast enhancemt effect to improve the distinction between normal liver and target HCC tissues. The acidic pH of the tumor microenvironment triggers the disassembly of the RIAs, which leads to a drastic decrease in their relaxivity ratio (r 2/r 1), thus converting the RIAs from a T2 to T1 contrast agent. This inverse contrast enhancement of normal liver darkening and HCC brightening under T1 imaging mode was validated on an orthotopic HCC model. Our design provides a novel strategy for the exploitation of the next-generation intelligent MRI contrast agents.
•Chemical aspects of the ligands design for nanomaterial synthesis and assembly.•The effect of surface ligands on physical and chemical properties of nanomaterials.•The effect of ligands on nano–bio ...interface.•The role of surface ligands on colloidal stability, biocompatibility and multifunctionality of nanomaterials for biomedical applications.
Nanotechnology has received extraordinary attention recently due to its burgeoning role in biomedical science. The materials composing the nanoparticles produce fascinating and diverse functionalities as a result of their exceptionally small size. In fact, even seemingly insignificant changes in particle size can have profound effects on these properties. Thus size control, both during synthesis and in particle suspensions, is a sine qua non for functionality. This can be accomplished by masking the particle surface with a multitude of different ligands. Not only can surface ligands constrain the growth of nucleation, they can also direct the shape of crystallization. However no single ligand can do everything. Fortunately ligands are essentially fungible and can be exchanged at various times to confer the desired properties to the particle. This can include protecting the particle from harsh aqueous conditions, such as pH extremes, maximizing optical properties for diagnostics or shielding the particle from potentially hostile conditions found in the body. Because these moieties interact ubiquitously with various biological materials, particularly proteins, there needs to be a rationalized design of surface ligands. The design of the ligand can have crucial effects on biodistribution as well as evasion of biological defenses. Ligands can even be designed to provide new functionality in response to various environmental stimuli to improve their therapeutic or diagnostic capabilities. Considering the importance of ligands then on this emerging field, this review will thoroughly consider the ligand design for the various steps of nanodevelopment, from synthesis and assembly through biomedical translation.
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