Ultrasmall Iron Oxide Research Articles

Single cell combined with laser ablation ICP-MS to study cisplatinum (IV) loaded nanoparticles penetration pathways in osteosarcoma spheroids

Background3D cellular structures have been considered the following step in the evaluation of drugs penetration after 2D cultures since they are more physiologically representative in cancer cell biology. Here the penetration capabilities of Pt (IV)-loaded ultrasmall iron oxide nanoparticles in 143B osteosarcoma multicellular spheroids of different sizes is conducted by a multidimensional quantitative approach. Single cell (SC) and imaging techniques (laser ablation, LA) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) are used to visualize their penetration pathways and distribution in comparison to those of cisplatin. ResultsThe analysis of Pt in disaggregated individual cells from spheroids shows levels of incorporation dependent on the spheroid surface to volume ratio and considerably higher than those observed for cisplatin. These results in combination with the total Pt determination in the complete spheroids reveal a preferential transcellular incorporation pathway of the Pt(IV)-loaded NPs. Elemental imaging by LA-ICP-MS shows the co—localization of Pt/Fe in hot spots at distances up to 100 μm from the spheroid surface reaching concentrations of Pt up to 200 μg g−1 when exposed to Pt(IV)-loaded NPs. A more homogeneous distribution all along the spheroid is observed in the cisplatin-treated models. SignificanceThe multidimensional ICP-MS based analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nano-transported drugs to be applied in the design of nanoparticles with high accumulation at a target site.

Clustered ultra-small iron oxide nanoparticles as potential T1/T2 dual–modal magnetic resonance imaging contrast agents and application to tumor model

Many studies have been conducted on the use of ultra-small iron oxide nanoparticles (USIONs) (d < 3 nm) as potential positive magnetic resonance imaging (MRI)-contrast agents (CAs); however, there is dearth of research on clustered USIONs. In this study, nearly monodispersed clustered USIONs were synthesized using a simple two-step one-pot polyol method. First, USIONs (d = 2.7 nm) were synthesized, and clustered USIONs (d = 27.9 nm) were subsequently synthesized through multiple cross-linking of USIONs with poly(acrylic acid-co-maleic acid) (PAAMA) polymers with many -COOH groups. The clustered PAAMA-USIONs exhibited very weak ferromagnetism owing to the magnetic interaction between superparamagnetic USIONs; this was evidenced by their appreciable r1= 3.9 s‒1mM‒1and high r2/r1ratio of 14.6. Their ability to function as a dual-modal T1/T2MRI-CA in T1-weighted MRI was demonstrated when they simultaneously exhibited positive and negative contrasts in T1-weighted MRI of tumor model mice after intravenous injection. They displayed positive contrasts at the kidneys, bladder, heart, and aorta and negative contrasts at the liver and tumor.&#xD.

Using Adaptive Imaging Parameters to Improve PEGylated Ultrasmall Iron Oxide Nanoparticles-Enhanced Magnetic Resonance Angiography.

The PEGylated ultrasmall iron oxide nanoparticles (PUSIONPs) exhibit longer blood residence time and better biodegradability than conventional gadolinium-based contrast agents (GBCAs), enabling prolonged acquisitions in contrast-enhanced magnetic resonance angiography (CE-MRA) applications. The image quality of CE-MRA is dependent on the contrast agent concentration and the parameters of the pulse sequences. Here, a closed-form mathematical model is demonstrated and validated to automatically optimize the concentration, echo time (TE), repetition time (TR) and flip angle (FA). The pharmacokinetic studies are performed to estimate the dynamic intravascular concentrations within 12h postinjection, and the adaptive concentration-dependent sequence parameters are determined to achieve optimal signal enhancement during a prolonged measurement window. The presented model is tested on phantom and in vivo rat images acquired from a 3T scanner. Imaging results demonstrate excellent agreement between experimental measurements and theoretical predictions, and the adaptive sequence parameters obtain better signal enhancement than the fixed ones. The low-dose PUSIONPs (0.03mmol kg-1 and 0.05mmol kg-1) give a comparable signal intensity to the high-dose one (0.10mmol kg-1) within 2h postinjection. The presented mathematical model provides guidance for the optimization of the concentration and sequence parameters in PUSIONPs-enhanced MRA, and has great potential for further clinical translation.

Trapped in Endosome PEGylated Ultra-Small Iron Oxide Nanoparticles Enable Extraordinarily High MR Imaging Contrast for Hepatocellular Carcinomas.

The early diagnosis of hepatocellular carcinomas (HCCs) remains challenging in the clinic. Primovist-enhanced magnetic resonance imaging (MRI) aids HCC diagnosis but loses sensitivity for tumors <2cm. Therefore, developing advanced MRI contrast agents is imperative for improving the diagnostic accuracy of HCCs in very-early-stage. To address this challenge, PEGylated ultra-small iron oxide nanoparticles (PUSIONPs) are synthesized and employed as liver-specific T1 MRI contrast agents. Intravenous delivery produces simultaneous hyperintense HCC and hypointense hepatic parenchyma signals on T1 imaging, creating an extraordinarily high tumor-to-liver contrast. Systematic studies uncover PUSIONP distribution in hepatic parenchyma, HCC lesions at the organ, tissue, cellular, and subcellular levels, revealing endosomal confinement of PUSIONP without aggregation. By mimicking such situations, the dependency of relaxometric properties on local PUSIONP concentration is investigated, emphasizing the key role of different endosomal concentrations in liver and tumor cells for high tumor-to-liver contrast and clear tumor boundaries. These findings offer exceptional imaging capabilities for early HCC diagnosis, potentially benefiting real HCC patients.

Three-Dimensional Label-Free Observing of the Self-Assembled Nanoparticles inside a Single Cell at Nanoscale Resolution.

Understanding the intracellular behavior of nanoparticles (NPs) plays a key role in optimizing the self-assembly performance of nanomedicine. However, conducting the 3D, label-free, quantitative observation of self-assembled NPs within intact single cells remains a substantial challenge in complicated intracellular environments. Here, we propose a deep learning combined synchrotron radiation hard X-ray nanotomography approach to visualize the self-assembled ultrasmall iron oxide (USIO) NPs in a single cell. The method allows us to explore comprehensive information on NPs, such as their distribution, morphology, location, and interaction with cell organelles, and provides quantitative analysis of the heterogeneous size and morphologies of USIO NPs under diverse conditions. This label-free, in situ method provides a tool for precise characterization of intracellular self-assembled NPs to improve the evaluation and design of a bioresponsive nanomedicine.

Erythrocyte-Membrane-Camouflaged Magnetic Nanocapsules With Photothermal/Magnetothermal Effects for Thrombolysis.

Venous/arterial thrombosis poses significant threats to human health. However, drug-enabled thrombolysis treatment often encounters challenges such as short half-life and low bioavailability. To address these issues, the design of erythrocyte-membrane (EM) camouflaged nanocapsules (USIO/UK@EM) incorporating ultra-small iron oxide (USIO) and urokinase (UK) drug, which exhibits remarkable photothermal/magnetothermal effects and drug delivery ability for venous/arterial thrombolysis, is reported. USIO, UK, and EM are coextruded to fabricate USIO/UK@EM with average sizes of 103.7nm. As USIO/UK@EM possesses wide photoabsorption and good magnetic properties, its solution demonstrates a temperature increase to 41.8-42.9°C within 5min when exposed to an 808nm laser (0.33mW cm-2) or alternating magnetic field (AMF). Such photothermal/magnetothermal effect along with UK confers impressive thrombolytic rates of 82.4% and 74.2%, higher than that (≈15%) achieved by UK alone. Further, the EM coating extends the circulating half-life (t1/2 = 3.28h). When USIO/UK@EM is administered to mice and rabbits, tail vein thrombus in mice and femoral artery thrombus in rabbits can be dissolved by the synergetic effect of thermothrombolysis and UK. Therefore, this study not only offers insights into the rational design of multifunctional biomimetic nanocapsules but also showcases a promising thrombolysis strategy utilizing nanomedicine.

Acidic tumor microenvironment-activated MRI nanoprobes for modulation and visualization of anti-PD-L1 immunotherapy

Tumor acidity has emerged as a pivotal regulator of immune checkpoint blockade (ICB). However, acidity-based therapy presents challenges of low efficiency and lack of reliable imaging technology for assessing the immune response. Here we report a magnetic resonance imaging (MRI)-guided ICB therapy (MRGIT) strategy to modulate and visualize the efficacy of anti-PD-L1 in pancreatic ductal adenocarcinoma (PDAC). MRGIT was achieved by a pH responsive nanoprobe (APPAM@U-104) composed of ultrasmall iron oxide nanoparticles (USIONs) and a tumor pH regulator (U-104). Notably, the nanoprobes exhibited a T1 “ON” MR signal in acidic tumors but switched to a T2 “ON” MR signal in a neutralized tumor microenvironment, resulting in a switchable MR signal from T1 to T2 during real-time MRI monitoring. Moreover, the switch of MR signals can serve as an indicator for alleviating tumor immune suppression, thus guiding the timing of anti-PD-L1 therapy. Our results revealed that the MRGIT strategy can potentiate the antitumor efficacy of anti-PD-L1 against pancreatic tumors. Collectively, this strategy sensitively regulates and recognizes tumor acidosis, thus paving the way for the modulation and noninvasive monitoring of anti-PD-L1 efficacy in PDAC.

Pilot-scale co-precipitation synthesis of a novel active ingredient made of ultrasmall iron (oxyhydr)oxide nanoparticles for the treatment of hyperphosphatemia.

Due to its simplicity, co-precipitation is the most commonly used method for producing iron (oxyhydr)oxide nanoparticles. However, it is reported to be sensitive to changes in process parameters, which complicates scale-up and is why only volumes up to 1.2 L have been described in the literature. This study aims to demonstrate the scale-up of a co-precipitation synthesis to 100 L using the example of a new phosphate-binding active ingredient based on iron (oxyhydr)oxide. The synthesis was shown to be very robust to changes in synthesis parameters and stirrer geometries. The in vitro phosphate-binding efficacy and the yield were maintained in all five scales tested. Only the content of the components in the nanoparticles varied slightly. However, Mössbauer spectroscopy, dynamic light scattering (DLS), and attenuated total reflection Fourier transform infrared spectroscopy (FT-IR) revealed no evidence of structural changes, but a reduction in the size of the iron (oxyhydr)oxide cores and the total core-shell nanoparticle sizes. Overall, this study has successfully demonstrated that ultrasmall iron (oxyhydr)oxide nanoparticles can be produced on a pilot scale by co-precipitation with a yield of >40 g L-1.

Ultrasmall Mn-doped iron oxide nanoparticles with dual hepatobiliary and renal clearances for T1 MR liver imaging.

Although magnetic nanoparticles demonstrate significant potential as magnetic resonance imaging (MRI) contrast agents, their negative contrasts, liver accumulation, and limited excretion hinder their application. Herein, we developed ultrasmall Mn-doped iron oxide nanoparticles (UMIOs) with distinct advantages as T1 MRI contrast agents. Exceptionally small particle sizes (ca. 2 nm) and magnetization values (5 emu gMn+Fe-1) of UMIOs provided optimal T1 contrast effects with an ideally low r2/r1 value of ∼1. Furthermore, the use of Mn as a dopant facilitated hepatocyte uptake of the particles, allowing liver imaging. In animal studies, UMIOs exhibited significantly enhanced contrasts for sequential T1 imaging of blood vessels and the liver, distinguishing them from conventional magnetic nanoparticles. UMIOs were systematically cleared via dual hepatobiliary and renal excretion pathways, highlighting their safety profile. These characteristics imply substantial potential of UMIOs as T1 contrast agents for the accurate diagnosis of liver diseases.

Macrophage membrane-camouflaged nanoclusters of ultrasmall iron oxide nanoparticles for precision glioma theranostics.

Developing effective nanomedicines to cross the blood-brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs. The prepared MM-coated G-USIO NCs (G-USIO@MM NCs) with a mean size of 99.9 nm display tumor microenvironment (TME)-responsive gossypol and Fe release to promote intracellular ROS production and glutathione consumption. With the MM-mediated BBB crossing and glioma targeting, the G-USIO@MM NCs can specifically inhibit orthotopic glioma in vivo through the gossypol-mediated chemotherapy and Fe-mediated CDT. Meanwhile, USIO NPs can be dissociated from the NCs under the TME, thus allowing for effective T1-weighted glioma MR imaging. The developed G-USIO@MM NCs with simple components and drug as a crosslinker are promising for glioma theranostics, and may be extended to tackle other cancer types.

Ultrasmall iron oxide nanoparticles with MRgFUS for enhanced magnetic resonance imaging of orthotopic glioblastoma.

Ultrasmall iron oxide nanoparticles (USIO NPs) are expected to become the next generation T1 contrast agents; however, their diagnostic and therapeutic potential for primary brain tumors (such as glioblastoma multiforme, GBM) is yet to be explored. At present, the main challenge is the effective hindering of biological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Herein, we aimed to investigate whether the USIO NPs, in combination with MR-guided focused ultrasound (MRgFUS), could intensify MR imaging of GBM. In this study, we presented zwitterionic USIO NPs for enhanced MR imaging of both xenografted and orthotopic GBM mouse models. We first synthesized citric-stabilized USIO NPs with a size of 3.19 ± 0.76 nm, modified with ethylenediamine, and decorated with 1,3-propanesultone (1,3-PS) to form USIO NPs-1,3-PS. The obtained USIO NPs-1,3-PS exhibited good cytocompatibility and cellular uptake efficiency. MRgFUS, in combination with microbubbles, provided a non-invasive and safe technique for BBB opening, which, in turn, promoted the delivery of USIO NPs-1,3-PS in orthotopic GBM. This developed USIO NP nanoplatform may improve the precision imaging of solid tumors and therapeutic efficacy in the central nervous system.

Process development for pilot-scale spray drying of ultrasmall iron (oxyhydr)oxide nanoparticles

In manufacturing iron (oxyhydr)oxide nanoparticles, drying is often necessary to increase stability or to enable granulation and tableting. Lyophilization is a simple drying method, although it is characterized by high energy consumption and high cost. This study aims to demonstrate that spray drying is a suitable alternative for preparing iron (oxyhydr)oxide nanoparticles. A Design of Experiment approach was used varying the inlet air temperature, feed flow rate, and feed concentration. Especially a low feed flow rate was beneficial for low residual moisture (< 7%) and high yield (> 80%). The process was subsequently transferred to pilot scale at a feed flow rate of 2.3 kg/h. The nanomaterial had comparable properties and efficacy to the freeze-dried product. However, about 15% lower yield and 35% lower energy consumption were found for spray drying the nanoparticles. This study shows that spray drying is a suitable alternative to freeze drying for iron (oxyhydr)oxide nanoparticles.

Exploring atherosclerosis imaging with contrast-enhanced MRI using PEGylated ultrasmall iron oxide nanoparticles.

Plaque rupture is a critical concern due to its potential for severe outcomes such as cerebral infarction and myocardial infarction, underscoring the urgency of noninvasive early diagnosis. Magnetic resonance imaging (MRI) has gained prominence in plaque imaging, leveraging its noninvasiveness, high spatial resolution, and lack of ionizing radiation. Ultrasmall iron oxides, when modified with polyethylene glycol, exhibit prolonged blood circulation and passive targeting toward plaque sites, rendering them conducive for MRI. In this study, we synthesized ultrasmall iron oxide nanoparticles of approximately 3nm via high-temperature thermal decomposition. Subsequent surface modification facilitated the creation of a dual-modality magnetic resonance/fluorescence probe. Upon intravenous administration of the probes, MRI assessment of atherosclerotic plaques and diagnostic evaluation were conducted. The application of Flash-3D sequence imaging revealed vascular constriction at lesion sites, accompanied by a gradual signal amplification postprobe injection. T1-weighted imaging of the carotid artery unveiled a progressive signal ratio increase between plaques and controls within 72h post-administration. Fluorescence imaging of isolated carotid arteries exhibited incremental lesion-to-control signal ratios. Additionally, T1 imaging of the aorta demonstrated an evolving signal enhancement over 48h. Therefore, the ultrasmall iron oxide nanoparticles hold immense promise for early and noninvasive diagnosis of plaques, providing an avenue for dynamic evaluation over an extended time frame.

Stimuli-Responsive Codelivery System Self-Assembled from in Situ Dynamic Covalent Reaction of Macrocyclic Disulfides for Cancer Magnetic Resonance Imaging and Chemotherapy.

Supramolecular self-assembly has gained increasing attention to construct multicomponent drug delivery systems for cancer diagnosis and therapy. Despite that these self-assembled nanosystems present surprising properties beyond that of each subcomponent, the spontaneous nature of co-self-assembly causes significant difficulties in control of the synthesis process and consequently leads to unsatisfactory influences in downstream applications. Hence, we utlized an in situ dynamic covalent reaction based on thiol-disulfide exchange to slowly produce disulfide macrocycles, which subsequently triggered the co-self-assembly of an anticancer drug (doxorubicin, DOX) and a magnetic resonance imaging (MRI) contrast agent of ultrasmall iron oxide nanoparticles (IO NPs). It showed concentration regulation of macrocyclic disulfides, DOX, and IO NPs by a dynamic covalent self-assembly (DCS) strategy, resulting in a stable codelivery nanosystem with high drug loading efficiency of 37.36%. More importantly, disulfide macrocycles in the codelivery system could be reduced and broken by glutathione (GSH) in tumor cells, thus leading to disassembly of nanostructures and intellgent release of drugs. These stimuli-responsive performances have been investigated via morphologies and molecular structures, revealing greatly enhanced dual-modal MRI abilities and smart drug release under the trigger of GSH. Moreover, the codelivery system conjugated with a targeting molecule of cyclic Arg-Gly-Asp (cRGD) exhibited significant biocompatibility, MR imaging, and chemotherapeutic anticancer effect in vitro and in vivo. These results indicated that in situ dynamic covalent chemistry enhanced the control over co-self-assembly and paved the way to develop more potential drug delivery systems.

Single-Cell ICP-MS in Combination with Fluorescence-Activated Cell Sorting for Investigating the Effects of Nanotransported Cisplatin(IV) Prodrugs.

The combined use of fluorescence-activated cell sorting (FACS) and single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) is reported, for the first time, in this work. It is applied to evaluate the differences between the cellular uptake of ultrasmall iron oxide nanoparticles (FeNPs) loaded with cisplatin(IV) prodrug (FeNPs-Pt(IV)) and cisplatin regarding cell viability. For this aim, FACS is applied to separate viable, apoptotic, and necrotic A2780 ovarian cancer cells after exposing them to the nanotransported prodrug and cisplatin, respectively. The different sorted cell populations are individually analyzed using quantitative SC-ICP-MS to address the intracellular amount of Pt. The highest Pt intracellular content occurs in the apoptotic cell population (about 2.1 fg Pt/cell) with a narrow intercellular distribution when using FeNPs-Pt(IV) nanoprodrug and containing the largest number of cells (75% of the total). In the case of the cisplatin-treated cells, the highest Pt content (about 1.6 fg Pt/cell) could be determined in the viable sorted cell population. The combined methodology, never explored before, permits a more accurate picture of the effect of the intracellular drug content together with the cell death mechanisms associated with the free drug and the nanotransported prodrug, respectively, and opens the door to many possible single-cell experiments in sorted cell populations.

Scalable diafiltration process for the purification of a colloidal dispersion of ultrasmall iron (oxyhydr)oxide-based nanoparticles

The process description for large-scale production of iron (oxyhydr)oxide nanoparticles is currently receiving greater attention, with cost-effective industrial production usually crucial for economic application. In this context, the purification step is often price-determining in the production process. Dialysis as membrane-assisted purification is one of the most widely used methods in the case of iron (oxyhydr)oxide nanoparticles but has very limited suitability for large-scale production. This study aims to demonstrate for the first time that cross–flow filtration is a suitable alternative for the industrial production of ultrasmall iron (oxyhydr)oxide nanoparticles. This study includes the development of a concentration and diafiltration process for ultrasmall iron (oxyhydr)oxide nanoparticles on a laboratory scale, upscaling for the purification of 75 kg nanoparticle suspension, and comparison with dialysis purification.In summary, the optimized filtration process is characterized by a consistent and high product quality and high product yield, comparable to dialysis purification and suitable for pilot-scale production. Finally, the results demonstrated that the developed process is an economically attractive alternative to dialysis. The processing time is reduced by 79 %, the water consumption is 96 % lower, and 66 % of the material costs are saved.

A Biomimetic Nanogel System Restores Macrophage Phagocytosis for Magnetic Resonance Imaging-Guided Synergistic Chemoimmunotherapy of Breast Cancer.

Novel strategies to facilitate tumor-specific drug delivery and restore immune attacks remain to be developed to overcome the current limitations of chemotherapy. Herein, a cancer cell membrane (CM)-camouflaged and ultrasmall iron oxide nanoparticles (USIO NPs)-loaded polyethylenimine nanogel (NG) system is reported to co-deliver docetaxel (DTX) and CD47 siRNA (siCD47). The prepared co-delivery system exhibits good colloidal stability, biocompatibility, and r1 relaxivity (1.35 mM-1 s-1 ) and enables redox-responsive release of the loaded DTX in the tumor microenvironment. The NG system realizes homologous targeting delivery of DTX and siCD47 to murine breast cancer cells (4T1 cells) for efficient chemotherapy and gene silencing; thus, inducing immunogenic cell death (ICD) and restoring macrophage phagocytic effect through downregulation of "don't eat me" signals on cancer cells. Likewise, the co-delivery system can also act on macrophages to promote their M1 polarization, which can be combined with DTX-mediated ICD and antibody-mediated immune checkpoint blockade to generate effector T cells for robust chemoimmunotherapy. Further, the USIO NPs-incorporated NG system also allows for magnetic resonance imaging of tumors. The developed biomimetic NG system acting on both cancer cells and macrophages holds a promising potential for macrophage phagocytosis-restored chemoimmunotherapy.

GSH/APE1 Cascade-Activated Nanoplatform for Imaging Therapy Resistance Dynamics and Enzyme-Mediated Adaptive Ferroptosis.

Ferroptosis, as a type of programmed cell death process, enables effective damage to various cancer cells. However, we discovered that persistent oxidative stress during ferroptosis can upregulate the apurinic/apyrimidinic endonuclease 1 (APE1) protein that induces therapeutic resistance ("ferroptosis resistance"), resulting in an unsatisfactory treatment outcome. To address APE1-induced therapeutic resistance, we developed a GSH/APE1 cascade activated therapeutic nanoplatform (GAN). Specifically, the GAN is self-assembled by DNA-functionalized ultrasmall iron oxide nanoparticles and further loaded with drug molecules (drug-GAN). GSH-triggered GAN disassembly can "turn on" the catalysis of GAN to induce efficient lipid peroxidation (LPO) for ferroptosis toward the tumor, which could upregulate APE1 expression. Subsequently, upregulated APE1 can further trigger accurate drug release for overcoming ferroptosis resistance and inducing the recovery of near-infrared fluorescence for imaging the dynamics of APE1. Importantly, adaptive drug release can overcome the adverse effects of APE1 upregulation by boosting intracellular ROS yield and increasing DNA damage, to offset APE1's functions of antioxidant and DNA repair, thus leading to adaptive ferroptosis. Moreover, with overexpressed GSH and upregulated APE1 in the tumor as stimuli, the therapeutic specificity of ferroptosis toward the tumor is greatly improved, which minimized nonspecific activation of catalysis and excessive drug release in normal tissues. Furthermore, a switchable MRI contrast from negative to positive is in sync with ferroptosis activation, which is beneficial for monitoring the ferroptosis process. Therefore, this adapted imaging and therapeutic nanoplatform can not only deliver GSH/APE1-activated lipid peroxide mediated adaptive synergistic therapy but also provided a switchable MRI/dual-channel fluorescence signal for monitoring ferroptosis activation, drug release, and therapy resistance dynamics in vivo, leading to high-specificity and high-efficiency adaptive ferroptosis therapy.

Theranostic RGD@Fe3O4-Au/Gd NPs for the targeted radiotherapy and MR imaging of breast cancer

BackgroundAs a radiosensitizing agent in magnetic resonance imaging (MRI), gadolinium is disadvantageous in that it confers a rather high toxicity and low longitudinal comfort time (r1). We hypothesized that gadolinium when combined with gold-coated iron oxide nanoparticles (NPs), might deliver better radiosensitization in MRI-based cancer theranostics. After being synthesized ligand/receptor RGD@Fe3O4-Au/Gd nanoparticles, they were characterized via some methods, such as visible–ultraviolet spectroscopy (UV–VIS), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscope (TEM). Using relaxometry, the parameters of contrast change in T1-weighted MRI and the rate of radiation sensitivity on cancerous (MCF-7, SK-BR-3 and MDA-MB-231 (and reference (MCF-10a) breast cell lines were investigated.ResultsThe presence of ultra-small iron oxide, gold, gadolinium, and RGD peptide as components of the RGD@Fe3O4-Au/Gd nanocomplex was confirmed by UV–visible, FTIR, EDX and XRD tests. With a size ranging from 4.124 nm (DLS) to 15 nm (TEM), these NPs exhibited a surface charge of –45.7 mV and a magnetic saturation of 3 emu/g. The concentrations of iron, gadolinium and gold samples in the nanocomplex were 1000, 1171 and 400 parts per million (ppm), respectively. In the relaxometry test, the rates of r2/r1 and r1 NPs were 1.56 and 23.5 mM−1 s−1. The dose increase factor for targeted (RGD@Fe3O4-Au/Gd) and non-targeted (Fe3O4-Au/Gd) NPs at 6 MV and 2 Gy was 89.1 and 59.1, respectively.ConclusionOwing to an enhanced signal-to-noise ratio (SNR), as confirmed by the MRI of RGD receptor-expressing MDA-MB-231 cells, RGD@Fe3O4-Au/Gd NPs were found to confer higher radiosensitization and an overall better performance as a novel radiosensitizer for MRI-based breast cancer theranostics than Fe3O4-Au/Gd nanocomplex.Graphical

A Selective Nano Cell Cycle Checkpoint Inhibitor Overcomes Leukemia Chemoresistance (Small 25/2023)

Nano Cell Cycle Checkpoint Inhibitors In article number 2300736, Daishun Ling, Fangyuan Li, and co-workers demonstrate that ultra-small iron oxide nanoparticles (IONPs) can serve as a selective nano cell cycle checkpoint inhibitor (NCCI) to catalyze the intracellular H2O2 into abundant ·OH, cleave heat shock protein 90 (Hsp90), and thus induce the degradation of the client protein ATR/CHK1, leading to the dysfunction of the G2/M checkpoint in acute myeloid leukemia (AML) cells. As a result, NCCI can interfere with the chemotherapy-induced DNA damage repair, which effectively reverses the chemoresistance of acute myeloid leukemia.