Magnetic nanoparticles (MNPs) have been extensively explored as magnetic resonance imaging (MRI) contrast agents. With the increasing complexity in the structure of modern MNPs, the classical ...Solomon–Bloembergen–Morgan and the outer‐sphere quantum mechanical theories established on simplistic models have encountered limitations for defining the emergent phenomena of relaxation enhancement in MRI. Recent progress in probing MRI relaxivity of MNPs based on structural features at the molecular and atomic scales is reviewed, namely, the structure–relaxivity relationships, including size, shape, crystal structure, surface modification, and assembled structure. A special emphasis is placed on bridging the gaps between classical simplistic models and modern MNPs with elegant structural complexity. In the pursuit of novel MRI contrast agents, it is hoped that this review will spur the critical thinking for design and engineering of novel MNPs for MRI applications across a broad spectrum of research fields.
Structure–relaxivity relationships between different structural features of magnetic nanoparticles (MNPs) and the resulting T1 and T2 relaxivities in magnetic resonance imaging (MRI) are reviewed. The factors of size, shape, crystal structure, surface functionality, and assembly structure of magnetic nanoparticles are summarized to decipher how physical properties of MNPs influence proton relaxation in MRI.
Owing to their unique physical and chemical properties, magnetic iron oxide nanoparticles have become a powerful platform in many diverse aspects of biomedicine, including magnetic resonance imaging, ...drug and gene delivery, biological sensing, and hyperthermia. However, the biomedical applications of magnetic iron oxide nanoparticles arouse serious concerns about their pharmacokinetics, metabolism, and toxicity. In this review, the updated research on the biomedical applications and potential toxicity of magnetic iron oxide nanoparticles is summarized. Much more effort is required to develop magnetic iron oxide nanoparticles with improved biocompatible surface engineering to achieve minimal toxicity, for various applications in biomedicine.
Magnetic iron oxide nanoparticles have become a powerful platform in many diverse aspects of biomedicine, including magnetic resonance imaging, drug and gene delivery, biological sensing, and hyperthermia. However, the biomedical applications of magnetic iron oxide nanoparticles arouse serious concerns about their pharmacokinetics, metabolism and toxicity. This review presents a broad overview of the biomedical applications and available toxicity assessments of magnetic iron oxide nanoparticles.
The combination of nanotechnology and molecular biology has developed into an emerging research area: nanobiotechnology. Magnetic nanoparticles are well-established nanomaterials that offer ...controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI). As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging. Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional magnetic nanoparticles. Currently, there are two strategies to fabricate magnetic nanoparticle-based multifunctional nanostructures. The first, molecular functionalization, involves attaching antibodies, proteins, and dyes to the magnetic nanoparticles. The other method integrates the magnetic nanoparticles with other functional nanocomponents, such as quantum dots (QDs) or metallic nanoparticles. Because they can exhibit several features synergistically and deliver more than one function simultaneously, such multifunctional magnetic nanoparticles could have unique advantages in biomedical applications. In this Account, we review examples of the design and biomedical application of multifunctional magnetic nanoparticles. After their conjugation with proper ligands, antibodies, or proteins, the biofunctional magnetic nanoparticles exhibit highly selective binding. These results indicate that such nanoparticles could be applied to biological medical problems such as protein purification, bacterial detection, and toxin decorporation. The hybrid nanostructures, which combine magnetic nanoparticles with other nanocomponents, exhibit paramagnetism alongside features such as fluorescence or enhanced optical contrast. Such structures could provide a platform for enhanced medical imaging and controlled drug delivery. We expect that the combination of unique structural characteristics and integrated functions of multicomponent magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nanomedicine.
Multifunctional nanocomposites have the potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure. Herein, we synthesize Fe3O4@polydopamine core-shell ...nanocomposites (Fe3O4@PDA NCs) through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto a wide range of materials including Fe3O4 nanoparticles used here. In such nanocomposites, PDA provides a number of advantages, such as near-infrared absorption, high fluorescence quenching efficiency, and a surface for further functionalization with biomolecules. We demonstrate the ability of the Fe3O4@PDA NCs to act as theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal therapy. This work would stimulate interest in the use of PDA as a useful material to construct multifunctional nanocomposites for biomedical applications.
Near-infrared fluorescence (NIRF) imaging promises to improve cancer imaging and management; advances in nanomaterials allow scientists to combine new nanoparticles with NIRF imaging techniques, ...thereby fulfilling this promise. Here, we present a synopsis of current developments in NIRF nanoprobes, their use in imaging small living subjects, their pharmacokinetics and toxicity, and finally their integration into multimodal imaging strategies. We also discuss challenges impeding the clinical translation of NIRF nanoprobes for molecular imaging of cancer. Whereas utilization of most NIRF nanoprobes remains at a proof-of-principle stage, optimizing the impact of nanomedicine in cancer patient diagnosis and management will probably be realized through persistent interdisciplinary amalgamation of diverse research fields.
Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is ...still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau-Lifshitz-Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.
Visualization of biological targets such as crucial cells and biomolecules in living subjects is critical for the studies of important biological processes. Though 1H magnetic resonance imaging (MRI) ...has demonstrated its power in offering detailed anatomical and pathological information, its capacity for in vivo tracking of biological targets is limited by the high biological background of 1H. 19F distinguishes itself from its competitors as an exceptional complement to 1H in MRI through its high sensitivity, low biological background, and broad chemical shift range. The specificity and sensitivity of 19F MRI can be further boosted with activatable nanoprobes. The advantages of 19F MRI with activatable nanoprobes enable in vivo detection and imaging at the cellular or even molecular level in deep tissues, rendering this technique appealing as a potential solution for visualization of biological targets in living subjects. Here, recent progress over the past decades on activatable 19F MRI nanoprobes made from three major 19F‐containing compounds, as well as present challenges and potential opportunities, are summarized to provide a panoramic prospective for the people who are interested in this emerging and exciting field.
19F magnetic resonance imaging (MRI) with activatable nanoprobes enables real‐time, deep‐tissue, and background‐free imaging of cells and biomolecules in living subjects. Recent progress on activatable 19F MRI nanoprobes made from three major 19F‐containing compounds as well as present challenges and potential opportunities are discussed, giving more insights into activatable probe design for this emerging and encouraging field.
The need for better imaging assisted cancer therapy calls for new biocompatible agents with excellent imaging and therapeutic capabilities. This study successfully fabricates albumin‐cooperated human ...serum albumin (HSA)‐GGD‐ICG nanoparticles (NPs), which are comprised of a magnetic resonance (MR) contrast agent, glycyrrhetinic‐acid‐modified gadolinium (III)‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetate (GGD), and a fluorescence (FL) dye, indocyanine green (ICG), for multimodal MR/FL imaging assisted cancer therapy. These HSA‐GGD‐ICG NPs with excellent biocompatibility are stable under physiological conditions, and exhibit enhanced T1 contrast capability and improved fluorescence imaging capacity. In vitro experiments reveal an apparent effect of the NPs in killing tumor cells under low laser irradiation, due to the enhanced photothermal conversion efficiency (≈85.1%). Importantly, multimodal MR/FL imaging clearly shows the in vivo behaviors and the efficiency of tumor accumulation of HSA‐GGD‐ICG NPs, as confirmed by a pharmacokinetic study. With the guidance of multimodal imaging, photothermal therapy is subsequently conducted, which demonstrates again high photothermal conversion capability for eliminating tumors without relapse. Notably, real‐time monitoring of tumor ablation for prognosis and therapy evaluation is also achieved by MR imaging. This strategy of constructing nanoplatforms through albumin‐mediated methods is both convenient and efficient, which would enlighten the design of multimodal imaging assisted cancer therapy for potential clinical translation.
A new type of biocompatible albumin‐cooperated nanoparticles (NPs) are fabricated for multimodal imaging assisted cancer therapy. These NPs exhibit enhanced T1 contrast capability and improved fluorescence imaging capacity. With the guidance of multimodal imaging, photothermal therapy is demonstrated for eliminating tumors without relapse. Moreover, real‐time monitoring of tumor ablation for prognosis analysis is achieved by magnetic resonance imaging.
Iron oxide nanoparticle (IONP) with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging (MRI) contrast agent (CA) for long time. However, a review ...which comprehensively summarizes the recent development of IONP as traditional T2 CA and its new application for different modality of MRI, such as T1 imaging, simultaneous T2/T1 or MRI/other imaging modality, and as environment responsive CA is rare. This review starts with an investigation of direction on the development of high-performance MRI CA in both T2 and T1 modal based on quantum mechanical outer sphere and Solomon–Bloembergen–Morgan (SBM) theory. Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters, including magnetization, size, effective radius, inhomogeneity of surrounding generated magnetic field, crystal phase, coordination number of water, electronic relaxation time, and surface modification are summarized. Besides the strategies to improve r2 or r1 values, strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects, those are introducing second imaging modality to increase the imaging accuracy, endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue, and optimizing the interface structure to improve the accumulation amount of IONP in lesion. This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs. It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.
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•T2 contrast capacity of iron oxide nanoparticles (IONPs) could be improved based on quantum mechanical outer sphere theory.•IONPs could be expand to be used as effective T1 CAs by improving q value, extending τs, and optimizing interface structure.•Environment responsive MRI CAs have been developed to improve the diagnosis accuracy.•Introducing other imaging contrast moiety into IONPs could increase the contrast efficiency.•Optimizing in vivo behavior of IONPs have been proved to enlarge the signal difference between normal tissue and lesion.
Tyrosinase is an important marker of human diseases such as the neurodegeneration associated with Parkinson's disease and melanoma. Sensitive detection of tyrosinase activity in vitro and inside ...cells is of great significance to medical diagnostics and skin disorder treatments. With unique photophysical properties, semiconductor quantum dots (QDs) are employed as photoluminescent platforms for various biosensing, in particular for the detection of enzyme activities. In this work, QDs are functionalized with tyrosine and zwitterionic molecules to construct a nanometer‐scale scaffold (QD‐Tyr conjugate), and this is used to test tyrosinase activity in vitro and inside cells. Tyrosinase oxidizes tyrosine to dopachrome and switches on the electron‐transfer access, which relates to fluorescence quenching. High quenching efficiency is achieved by shortening the distance between the electron donors and acceptors, which is attributed to the small size of the conjugated tyrosine. Enzymatic process curves reveal the enhanced enzymatic activity on the conjugated nanoparticle substrate, which leads to highly sensitive detection of tyrosinase (as low as 1 nM). It is also demonstrated that QD‐Tyr conjugates can sensitively probe intracellular tyrosinase in melanoma cells, which promises great potential in disease monitoring and medical diagnostics.
Sensitive detection of tyrosinase activity is of great significance to medical diagnostics and skin disorder treatments. Quantum dot (QD)‐Tyr conjugates are finely constructed by functionalizing tyrosine onto the QDs with a zwitterionic coating for tyrosinase analysis, which holds great promises for in vitro diagnostics (IVD) and disease‐monitoring applications.
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