Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications.
Multifunctional nanoparticles; magnetic nanoparticles; targeting ligand; bioconjugation; surface engineering; long circulation
Nanoparticles with gold shell and iron core have unique optical and magnetic properties which can be utilized for simultaneous detection and treatment strategies. Several nanoparticles have been synthesized and shown to mediate a variety of potential applications in biomedicine, including cancer molecular optical and magnetic resonance imaging, controlled drug delivery, and photothermal ablation therapy. However, to be effective, these nanoparticles must be delivered efficiently into their targets. In this review, we will provide an updated summary of the gold-shelled magnetic nanoparticles that have been synthesized, methods for characterization, and their potential for cancer diagnosis and treatment. We will also discuss the biological barriers that need to be overcome for the effective delivery of these nanoparticles. The desired nanoparticle characteristics needed to evade these biological barriers were also explained. Hopefully, this review will help researchers in designing nanoparticles by carefully choosing the optimum size, shape, surface charge, and surface coating.
Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment have been mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, we present a nanoparticle system that demonstrates an alternative approach to the treatment of cancers, through the inhibition of cell invasion, while serving as a magnetic resonance and optical imaging contrast agent. The nanoparticle is comprised of an iron oxide nanoparticle core, conjugated with an amine-functionalized PEG silane and a small peptide, chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. We show that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of ~98% compared to unbound CTX (~45%). Significantly, our investigation from flow cytometry analysis, transmission electron microscopy and fluorescent imaging revealed that the CTX-enabled nanoparticles deactivated the membrane-bound matrix metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts that contain surface-expressed MMP-2 and volume-regulating ion channels through receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since upregulation and activity of MMP-2 have been observed in tumors of neuroectodermal origin, and in cancers of the breast, colon, skin, lung, prostate, ovaries and a host of others, this nanoparticle system can be potentially used for non-invasive diagnosis and treatment of a variety of cancer types.
nanoparticles; chlorotoxin; invasion inhibition; specific targeting; cancer; imaging; biological activity
Iron-oxide nanoparticles facilitate cancer diagnosis through enhanced contrast, selectively enhance tumor cell death with magnetic hyperthermia, and improve drug delivery with magnetic drug targeting. One application that remains largely unexplored is using the iron-oxide nanoparticles themselves to selectively inhibit tumor growth. In this leading opinion paper, we propose that high doses of iron-oxide nanoparticles can be used as a treatment for cancer by generating an oxidative assault against cancer. This proposal may be met with resistance considering the controversy surrounding iron in the field of cancer. Iron generates reactive oxygen species through the Fenton reaction, which may both cause – or cure cancer. Additionally, high demand for iron by cancer cells leads to contradictory therapeutic approaches: iron deprivation or overdose are both potential cancer therapies.
Targeted biological therapies for hepatocellular cancer have shown minimal improvements in median survival. Multiple pathways to oncogenesis leading to rapid development of resistance to such therapies is a concern. Non-invasive radiofrequency field-induced targeted hyperthermia using nanoparticles is a radical departure from conventional modalities. In this paper we underscore the need for innovative strategies for the treatment of hepatocellular cancer, describe the central paradigm of targeted hyperthermia using non-invasive electromagnetic energy, review the process of characterization and modification of nanoparticles for the task, and summarize data from cell-based and animal-based models of hepatocellular cancer treated with non-invasive RF energy. Finally, future strategies and challenges in bringing this modality from bench to clinic are discussed.
In recent times, nanofluids have been studied by their thermal properties due to their variety of applications that range from photothermal therapy and radiofrequency hyperthermia (which have proven their potential use as coadjutants in these medical treatments for cancer diseases) to next-generation thermo-fluids. In this work, photoacoustic spectroscopy for a specific study of thermal diffusivity, as a function of particle size and concentration, on colloidal water-based gold nanofluids is reported. Gold nanoparticles were synthetized in the presence of hydroquinone through a seed-mediated growth with homogenous sizes and shapes in a range of 16 to 125 nm. The optical response, size and morphology of these nanoparticles were characterized using ultraviolet–visible spectroscopy and transmission electron microscopy, respectively. Thermal characterizations show a decrease in the thermal diffusivity ratio as the nanoparticle size is increased and an enhancement in thermal diffusivity ratio as nanoparticle concentration is added into the nanofluids. Compared with other techniques in the literature such as thermal lens and hot wire method, this photoacoustic technique shows an advantage in terms of precision, and with a small amount of sample required (500 μl), this technique might be suitable for the thermal diffusivity measurement of nanofluids. It is also a promising alternative to classical techniques.
Gold nanoparticles; Nanofluids; Photoacoustic; Thermal diffusivity
Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term “Hyperthermia” in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term “hyperthermia” by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled Drug delivery through Bond Breaking (DBB) and Hyperthermia-based controlled Drug delivery through Enhanced Permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities in the combination of hyperthermia-based therapy and controlled drug release paradigms for successful application in personalized medicine.
Hyperthermia; hyperthermia-based therapy; hyperthermia-based controlled drug delivery; core-shell magnetic nanoparticles; theranostics
Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired biological response. Of the nanomaterials studied, iron oxide nanoparticles have emerged as one of top candidates for cancer therapy due to their intrinsic superparamagnetism that enables no-invasive magnetic resonance imaging (MRI) and biodegradability favorable for in vivo application. A therapeutic superparamagnetic iron oxide nanoparticle (SPION) typically consists of three primary components: an iron oxide nanoparticle core that serves as both a carrier for therapeutics and contrast agent for MRI, a coating on the iron oxide nanoparticle that promotes favorable interactions between the SPION and biological system, and a therapeutic payload that performs designated function in vivo. Often, a targeting ligand is also included in the design that recognizes the receptors over-expressed on cancer cells. The body is a highly complex system that imposes multiple physiological and cellular barriers to foreign objects. Thus, the success of a therapeutic SPION largely relies on the proper design of the iron oxide core to ensure MRI detectability and more critically, the coating to render the ability to bypass these barriers.
Strategies to bypass the physiological barriers such as liver, kidneys, and spleen, involve tuning the overall size and surface chemistry of the SPION to maximize blood half-life and facilitate the navigation in the body. Strategies to bypass cellular barriers include the use of targeting agents to maximize uptake of the SPION by cancer cells, and employing materials that promote desired intracellular trafficking and enable controlled drug release.
The payload can be genes, proteins, chemotherapy drugs, or a combination of them. Each therapeutic requires a specific coating design to maximize the loading and achieve effective delivery and release. In this Account, we discuss the primary design parameters in developing therapeutic SPIONs with a focus on surface coating design to overcome the barriers imposed by the body’s defense system and provide examples of how these design parameters have been implemented to produce therapeutic SPIONs for specific therapeutic applications.
Although there are still challenges to be addressed, SPIONs show great promise in successful diagnosis and treatment of the most devastating cancers. Once critical design parameters have been optimized, these nanoparticles, combined with imaging modalities, can serve as a truly multi-functional theranostic agent that not only performs a therapeutic function, but provides instant treatment feedback for the physician to adjust the treatment plan.
Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential therapeutic applications in the central nervous system (CNS). They are useful as magnetic resonance imaging (MRI) contrast agents to evaluate: areas of blood–brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle synthesis strategies will allow for a rapidly expanding range of applications in patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis, multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may ultimately improve disease detection, therapeutic monitoring, and treatment efficacy especially in the context of antiangiogenic chemotherapy and antiinflammatory medications. The purpose of this review is to outline the current status of superparamagnetic iron oxide nanoparticles in the context of biomedical nanotechnology as they apply to diagnostic MRI and potential therapeutic applications in neurooncology and other CNS inflammatory conditions.
blood–brain barrier; CNS tumors; magnetic resonance imaging; ultrasmall superparamagnetic iron oxide nanoparticles
The magnetic nanoparticle has emerged as a potential multifunctional clinical tool that can provide cancer cell detection by magnetic resonance imaging (MRI) contrast enhancement as well as targeted cancer cell therapy. A major barrier in the use of nanotechnology for brain tumor applications is the difficulty in delivering nanoparticles to intracranial tumors. Iron oxide nanoparticles (IONPs; 10 nm in core size) conjugated to a purified antibody that selectively binds to the epidermal growth factor receptor (EGFR) deletion mutant (EGFRvIII) present on human glioblastoma multiforme (GBM) cells, were used for therapeutic targeting and MRI contrast enhancement of experimental glioblastoma both in vitro and in vivo after convection-enhanced delivery (CED). A significant decrease in glioblastoma cell survival was observed after nanoparticle treatment and no toxicity was observed with treatment of human astrocytes (P<0.001). Lower EGFR phosphorylation was found in glioblastoma cells after EGFRvIIIAb-IONP treatment. Apoptosis was determined to be the mode of cell death after treatment of GBM cells and glioblastoma stem cell (GSC)-containing neurospheres with EGFRvIIIAb-IONPs. MRI-guided CED of EGFRvIIIAb-IONPs allowed for the initial distribution of magnetic nanoparticles within or adjacent to intracranial human xenograft tumors and continued dispersion days later. A significant increase in animal survival was found after CED of magnetic nanoparticles (P<0.01) in mice implanted with highly tumorigenic glioblastoma xenografts (U87ΔEGFRvIII). IONPs conjugated to an antibody specific to the EGFRvIII deletion mutant constitutively expressed by human glioblastoma tumors can provide selective MRI contrast enhancement of tumor cells and targeted therapy of infiltrative glioblastoma cells after CED.
Glioblastoma; Magnetic Nanoparticles; Convection-Enhanced Delivery; MRI; EGFR
Gliomas are a group of heterogeneous primary central nervous system (CNS) tumors arising from the glial cells. Malignant gliomas account for a majority of malignant primary CNS tumors and are associated with high morbidity and mortality. Glioblastoma is the most frequent and malignant glioma, and despite the recent advances in diagnosis and new treatment options, its prognosis remains dismal. New opportunities for the development of effective therapies for malignant gliomas are urgently needed. Magnetic hyperthermia (MHT), which consists of heat generation in the region of the tumor through the application of magnetic nanoparticles subjected to an alternating magnetic field (AMF), has shown positive results in both preclinical and clinical assays. The aim of this review is to assess the relevance of hyperthermia induced by magnetic nanoparticles in the treatment of gliomas and to note the possible variations of the technique and its implication on the effectiveness of the treatment. We performed an electronic search in the literature from January 1990 to October 2010, in various databases, and after application of the inclusion criteria we obtained a total of 15 articles. In vitro studies and studies using animal models showed that MHT was effective in the promotion of tumor cell death and reduction of tumor mass or increase in survival. Two clinical studies showed that MHT could be applied safely and with few side effects. Some studies suggested that mechanisms of cell death, such as apoptosis, necrosis, and antitumor immune response were triggered by MHT. Based on these data, we could conclude that MHT proved to be efficient in most of the experiments, and that the improvement of the nanocomposites as well as the AMF equipment might contribute toward establishing MHT as a promising tool in the treatment of malignant gliomas.
brain tumor; magnetic hyperthermia; magnetic nanoparticle
Nanoparticles show tremendous promise in the safe and effective delivery of molecular adjuvants to enhance local cancer therapy. One important form of local cancer treatment that suffers from local recurrence and distant metastases is thermal therapy. Here we review a new concept involving the use of nanoparticle delivered adjuvants to “pre-condition” or alter the vascular and immunological biology of the tumor to enhance its susceptibility to thermal therapy. To this end, a number of opportunities to combine nanoparticles with vascular and immunologically active agents are reviewed. One specific example of pre-conditioning involves a gold nanoparticle tagged with a vascular targeting agent (i.e. TNF-α). This nanoparticle embodiment demonstrates pre-conditioning through a dramatic reduction in tumor blood flow and induction of vascular damage which recruits a strong and sustained inflammatory infiltrate in the tumor. The ability of this nanoparticle pre-conditioning to enhance subsequent heat or cold thermal therapy in a variety of tumor models is reviewed. Finally, the potential for future clinical imaging to judge the extent of pre-conditioning and thus the optimal timing and extent of combinatorial thermal therapy is discussed.
Nanoparticle pre-conditioning; colloidal gold; TNF-α; thermal therapy; hyperthermia; cryosurgery; cryotherapy; cancer
Targeted hyperthermia treatment using magnetic nanoparticles is a promising cancer therapy. However, the mechanisms of heat dissipation in the large alternating magnetic field used during such treatment have not been clarified. In this study, we numerically compared the magnetic loss in rotatable nanoparticles in aqueous media with that of non-rotatable nanoparticles anchored to localised structures. In the former, the relaxation loss in superparamagnetic nanoparticles has a secondary maximum because of slow rotation of the magnetic easy axis of each nanoparticle in the large field in addition to the known primary maximum caused by rapid Néel relaxation. Irradiation of rotatable ferromagnetic nanoparticles with a high-frequency axial field generates structures oriented in a longitudinal or planar direction irrespective of the free energy. Consequently, these dissipative structures significantly affect the conditions for maximum hysteresis loss. These findings shed new light on the design of targeted magnetic hyperthermia treatments.
Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.
cytotherapy; pancreatic cancer; disseminated peritoneal carcinomatosis; targeted magnetic hyperthermia; nanoparticles
Nanotechnology has prompted new and improved materials for biomedical applications with particular emphasis in therapy and diagnostics. Special interest has been directed at providing enhanced molecular therapeutics for cancer, where conventional approaches do not effectively differentiate between cancerous and normal cells; that is, they lack specificity. This normally causes systemic toxicity and severe and adverse side effects with concomitant loss of quality of life. Because of their small size, nanoparticles can readily interact with biomolecules both at surface and inside cells, yielding better signals and target specificity for diagnostics and therapeutics. This way, a variety of nanoparticles with the possibility of diversified modification with biomolecules have been investigated for biomedical applications including their use in highly sensitive imaging assays, thermal ablation, and radiotherapy enhancement as well as drug and gene delivery and silencing. Here, we review the available noble metal nanoparticles for cancer therapy, with particular focus on those already being translated into clinical settings.
In this study, magnetic iron oxide nanoparticle induced hyperthermia is applied for treatment of head and neck cancer using a mouse xenograft model of human head and neck cancer (Tu212 cell line). A hyperthermia system for heating iron oxide nanoparticles was developed by using alternating magnetic fields. Both theoretical simulation and experimental studies were performed to verify the thermotherapy effect. Experimental results showed that the temperature of the tumor center has dramatically elevated from around the room temperature to about 40oC within the first 5-10 minutes. Pathological studies demonstrate epithelial tumor cell destruction associated with the hyperthermia treatment.
hyperthermia; magnetic nanoparticles; head and neck cancer; mouse
The promise of hyperthermia has yet to be realized, but the fundamental idea and the effects of heat on (cancer) cells are well known. Cell death from exposure to heat is a function of both the intensity of the heat and the length of the exposure. Cells die by necrosis and by apoptosis. Sublethal heat doses sensitize cancer cells to radiation and drugs. Because of advances in chemistry and physics, harnessing the power of heat to kill cancer cells seems achievable now! Using novel systems embodied in the combination of molecular-targeted nanoparticles and hysteretic heating of the nanoparticles with “focused” alternating magnetic frequencies (AMFs), heat delivery can be better controlled. Importantly, hyperthermia does not damage, and may actually enhance, the immune system. Trials in patients are needed to settle the clinical role of new thermal treatment.
breast cancer; antibody; biotherapy; immunotherapy; imaging
Recent advances in cancer genomics have opened up unlimited potential for treating cancer by directly targeting culprit genes. However, novel delivery methods are needed in order for this potential to be translated into clinically viable treatments for patients. Magnetic nanoparticle technology offers the potential to achieve selective and efficient delivery of therapeutic genes by using external magnetic fields, and also allows simultaneous imaging to monitor the delivery in vivo. Compared to conventional gene delivery strategies, this technique has been shown to significantly increase gene delivery to human xenograft tumors models, as well as various internal organs (e.g. liver, kidney) and the central nervous system. Magnetic nanoparticle technology, therefore, has the potential to turn the challenge of gene therapy in vivo into a new frontier for cancer treatment.
magnetic targeting; magnetic nanoparticles; xenograft tumors models
Functionalization of monodisperse superparamagnetic magnetite (Fe3O4) nanoparticles for cell specific targeting is crucial for cancer diagnostics and therapeutics. Targeted magnetic nanoparticles can be used to enhance the tissue contrast in magnetic resonance imaging (MRI), to improve the efficiency in anticancer drug delivery, and to eliminate tumor cells by magnetic fluid hyperthermia. Herein we report the nucleus-targeting Fe3O4 nanoparticles functionalized with protein and nuclear localization signal (NLS) peptide. These NLS-coated nanoparticles were introduced into the HeLa cell cytoplasm and nucleus, where the particles were monodispersed and non-aggregated. The success of labeling was examined and identified by fluorescence microscopy and MRI. The work demonstrates that monodisperse magnetic nanoparticles can be readily functionalized and stabilized for potential diagnostic and therapeutic applications.
cell imaging; magnetic resonance imaging; magnetite; nanoparticles
There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy.
The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands.
The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection.
These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art.
Magnetic fluid hyperthermia as a cancer treatment method is an attractive alternative to other forms of hyperthermia. It is based on the heat released by magnetic nanoparticles subjected to an alternating magnetic field. Recent studies have shown that magnetic fluid hyperthermia-treated cells respond significantly better to chemotherapeutic treatment compared with cells treated with hot water hyperthermia under the same temperature conditions. We hypothesized that this synergistic effect is due to an additional stress on the cellular membrane, independent of the thermal heat dose effect that is induced by nanoparticles exposed to an alternating magnetic field. This would result in an increase in Cis-diammine-dichloroplatinum (II) (cDDP, cisplatin) uptake via passive transport. To test this hypothesis, we exposed cDDP-treated cells to extracellular copper in order to hinder the human cell copper transporter (hCTR1)-mediated active transport of cDDP. This, in turn, can increase the passive transport of the drug through the cell membrane. Our results did not show statistically significant differences in surviving fractions for cells treated concomitantly with magnetic fluid hyperthermia and cDDP, in the presence or absence of copper. Nonetheless, significant copper-dependent variations in cell survival were observed for samples treated with combined cDDP and hot water hyperthermia. These results correlated with platinum uptake studies, which showed that cells treated with magnetic fluid hyperthermia had higher platinum uptake than cells treated with hot water hyperthermia. Changes in membrane fluidity were tested through fluorescence anisotropy measurements using trimethylamine-diphenylhexatriene. Additional uptake studies were conducted with acridine orange and measured by flow cytometry. These studies indicated that magnetic fluid hyperthermia significantly increases cell membrane fluidity relative to hot water hyperthermia and untreated cells, and hence this could be a factor contributing to the increase of cDDP uptake in magnetic fluid hyperthermia-treated cells. Overall, our data provide convincing evidence that cell membrane permeability induced by magnetic fluid hyperthermia is significantly greater than that induced by hot water hyperthermia under similar temperature conditions, and is at least one of the mechanisms responsible for potentiation of cDDP by magnetic fluid hyperthermia in Caco-2 cells.
magnetic nanoparticles; synergistic effect; hot water hyperthermia; surviving fraction; viability ratio
Angiogenesis is disregulated in many diseased states, most notably in cancer. An emerging strategy for the development of therapies targeting tumor-associated angiogenesis is to harness the potential of nanotechnology to improve the pharmacology of chemotherapeutics, including anti-angiogenic agents. Nanoparticles confer several advantages over that of free drugs, including their capability to carry high payloads of therapeutic agents, confer increased half-life and reduced toxicity to the drugs, and provide means for selective targeting of the tumor tissue and vasculature. The plethora of nanovectors available, in addition to the various methods available to combine them with anti-angiogenic drugs, allows researchers to fine-tune the pharmacological profile of the drugs ad infinitum. Use of nanovectors has also opened up novel avenues for non-invasive imaging of tumor angiogenesis. Herein, we review the types of nanovector and therapeutic/diagnostic agent combinations used in targeting tumor angiogenesis.
We describe the synthesis, characterization, and use of hybrid nanoparticles with a superparamagnetic iron oxide (SPIO) core and a gold nanoshell. These multifunctional nanoparticles, designated SPIO-Au nanoshells, displayed superparamagnetic characteristics and a significant absorbance in the near-infrared (NIR) region of the electromagnetic spectrum. In addition, they exhibited high transverse relaxivity, r2, and a large r2/r1 ratio and therefore could be imaged by MRI to obtain T2-weighted images. Moreover, SPIO-Au nanoshells showed efficient photo-thermal effect when exposed to NIR light. The use of SPIO-Au nanoshells, with their combination of unique magnetic and optical properties, should enhance the efficacy of nanoshell-mediated photo-thermal therapy by making it possible to direct more nanoparticles to tumors through the application of external magnetic field and by permitting real-time in vivo MRI imaging of the distribution of the nanoparticles before, during, and after photo-thermal therapy.
Near-infrared; Nanoshells; Magnetic resonance imaging; Photo-thermal therapy
Importance of the field
Site-specific drug delivery is an important area of research that is anticipated to increase the efficacy of the drug and reduce potential side effects. Due to this, substantial work has been done developing non-invasive and targeted tumor treatment with nano-scale metallic particles.
Areas covered in this review
This review focuses on the work done in the last several years developing gold nanoparticles as cancer therapeutics and diagnostic agents. However, there are challenges in using gold nanoparticles as drug delivery systems such as biodistribution, pharmacokinetics, and possible toxicity. Approaches to limit these issues are proposed.
What the reader will gain
Different approaches from several different disciplines are discussed. Potential clinical applications of these engineered nanoparticles is also presented.
Take home message
Because of their unique size-dependent physico-chemical and optical properties, adaptability, sub-cellular size, and bio-compatibility, these nanosized carriers offer an apt means of transporting small molecules as well as biomacromoleculs to diseased cells/ tissues.
gold nanoparticles; cancer; drug delivery; drug targeting; diagnostics; biodistribution; thermal ablation; photodynamic therapy
In the presence of alternating-sinusoidal or rotating magnetic fields, magnetic nanoparticles will act to realign their magnetic moment with the applied magnetic field. The realignment is characterized by the nanoparticle’s time constant, τ. As the magnetic field frequency is increased, the nanoparticle’s magnetic moment lags the applied magnetic field at a constant angle for a given frequency, Ω, in rad/s. Associated with this misalignment is a power dissipation that increases the bulk magnetic fluid’s temperature which has been utilized as a method of magnetic nanoparticle hyperthermia, particularly suited for cancer in low-perfusion tissue (e.g., breast) where temperature increases of between 4°C and 7°C above the ambient in vivo temperature cause tumor hyperthermia. This work examines the rise in the magnetic fluid’s temperature in the MRI environment which is characterized by a large DC field, B0. Theoretical analysis and simulation is used to predict the effect of both alternating-sinusoidal and rotating magnetic fields transverse to B0. Results are presented for the expected temperature increase in small tumors (~1 cm radius) over an appropriate range of magnetic fluid concentrations (0.002 to 0.01 solid volume fraction) and nanoparticle radii (1 to 10 nm). The results indicate that significant heating can take place, even in low-field MRI systems where magnetic fluid saturation is not significant, with careful selection of the rotating or sinusoidal field parameters (field frequency and amplitude). The work indicates that it may be feasible to combine low-field MRI with a magnetic hyperthermia system using superparamagnetic iron oxide nanoparticles.
Hyperthermia; magnetic nanoparticles; MRI; heating; superparamagnetic fluids