Cancer theranostics is one of the most important approaches for detecting and treating patients at an early stage. To develop such a technique, accurate detection, specific targeting, and controlled ...delivery are the key components. Various kinds of nanoparticles have been proposed and demonstrated as potential nanovehicles for cancer theranostics. Among them, polymer-like dendrimers and copolymer-based core-shell nanoparticles could potentially be the best possible choices. At present, magnetic resonance imaging (MRI) is widely used for clinical purposes and is generally considered the most convenient and noninvasive imaging modality. Superparamagnetic iron oxide (SPIO) and gadolinium (Gd)-based dendrimers are the major nanostructures that are currently being investigated as nanovehicles for cancer theranostics using MRI. These structures are capable of specific targeting of tumors as well as controlled drug or gene delivery to tumor sites using pH, temperature, or alternating magnetic field (AMF)-controlled mechanisms. Recently, Gd-based pseudo-porous polymer-dendrimer supramolecular nanoparticles have shown 4-fold higher T
relaxivity along with highly efficient AMF-guided drug release properties. Core-shell copolymer-based nanovehicles are an equally attractive alternative for designing contrast agents and for delivering anti-cancer drugs. Various copolymer materials could be used as core and shell components to provide biostability, modifiable surface properties, and even adjustable imaging contrast enhancement. Recent advances and challenges in MRI cancer theranostics using dendrimer- and copolymer-based nanovehicles have been summarized in this review article, along with new unpublished research results from our laboratories.
Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or ...indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe
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and cobalt ferrite CoFe
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magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10-20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%-25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal heating efficiency in comparison with the optimal size predicted by previous models.
Abstract We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+ ·DOTA, through supramolecular assembly of ...molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+ ·DOTA-encapsulated supramolecular nanoparticles (Gd3+ ·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+ ·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+ ·DOTA⊂SNPs with an r1 of 17.3 s−1 mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1 -weighted imaging of Gd3+ ·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+ ·DTPA. A Gd3+ ·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+ ·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1 -weighted imaging after injecting Gd3+ ·DOTA⊂SNPs but not after injecting Gd3+ ·DTPA. The MRI results are supported by ICP-MS analysis ex vivo . These results show that Gd3+ ·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis.
Glioblastoma multiforme (GBM) is one of the most challenging diseases to treat in clinical oncology due to its high mortality rates and inefficient conventional treatment methods. Difficulties with ...early detection, post-surgical recurrences, and resistance to chemotherapy and/or radiotherapy are important reasons for the poor prognosis of those with GBM. Over the past few decades, magnetic resonance (MR) theranostics using magnetic nanoparticles has shown unique advantages and great promises for the diagnosis and treatment of cancers. Magnetic nanoparticles not only serve as "molecular beacons" to enhance tumor contrast in magnetic resonance imaging (MRI), but also serve as "molecular bullets" for targeted drug delivery, controlled release, and induced hyperthermia. Moreover, multiple functions of magnetic nanoparticles can be synergistically engineered into a single nanoplatform, making it possible to simultaneously image, treat, target, and monitor the targeted lesions. The multi-functionality of nanoparticles, also called nano-theranostics, gives rises to effective new approaches for combating GBM. In this work, recent research and progress concerning the applications of MR nano-theranostics on GBM using magnetic nanoparticles will be highlighted, focusing on topics such as diagnosis, therapy, targeting, and hyperthermia, as well as outstanding challenges for MR nanotheranostics in treating GBM. The conclusions are generally applicable to other types of brain tumors.
Carbon spheres with diameters between 400 and 2000 nm were synthesized in large quantities by catalytic chemical vapor deposition (CCVD) method using Kaolin supported transition metal salts (M=Fe, ...Co, Ni, etc.) as catalysts. The reaction conditions for the synthesis of carbon spheres in different sizes are described. The reactivity of the carbon spheres in various organic solvents is discussed. The as-synthesized carbon spheres are composed of unclosed graphene layers with the interlayer distances 0.33–0.35 nm. These carbon spheres have been characterized by SEM, TEM, HRTEM, XRD, Raman, ESR and SQUID magnetization techniques. From the ESR and SQUID the metallic nature of the carbon spheres is described.
Abstract Developing novel multifunctional nanoparticles (NPs) with robust preparation, low cost, high stability, and flexible functionalizability is highly desirable. This study provides an ...innovative platform, termed unibody core–shell (UCS), for this purpose. UCS is comprised of two covalent-bonded polymers differed only by the functional groups at the core and the shell. By conjugating Gd3+ at the stable core and encapsulating doxorubicin (Dox) at the shell in a pH-sensitive manner, we developed a theranostic NPs (UCS-Gd-Dox) that achieved a selective drug release (75% difference between pH 7.4 and 5.5) and MR imaging ( r1 = 0.9 and 14.5 m m−1 s−1 at pH 7.4 and 5.5, respectively). The anti-cancer effect of UCS-Gd-Dox is significantly better than free Dox in tumor-bearing mouse models, presumably due to enhanced permeability and retention effect and pH-triggered release. To the best of our knowledge, this is the simplest approach to obtain the theranostic NPs with Gd-conjugation and Dox doping.
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