Bimodal Imaging Research Articles

Sonoporation-assisted micelle delivery in subcutaneous glioma-bearing mice evaluated by PET/fluorescent bi-modal imaging.

Tumor-specific drug delivery is a major challenge for the pharmaceutical industry. Nanocarrier systems have been widely investigated to increase and control drug delivery to the heterogeneous tumor microenvironment. Classically, the uptake of nanocarriers by solid tumor tissues is mainly mediated by the enhanced permeability and retention effect (EPR). This EPR effect depends on the tumor type, its location, the physicochemical properties of the carriers, and the blood perfusion of the tumoral lesions. The main goal of this study was to evaluate in vivo tumor uptake of micelle carriers, assisted by microbubble/ultrasound sonoporation. Micelles were tracked using bi-modal imaging techniques to precisely localize both the nanocarrier and its payload. Micelles were loaded with a near infrared fluorophore and radiolabeled with zirconium-89. Their pharmacokinetics, biodistribution and passive tumor targeting properties were evaluated in a subcutaneous glioblastoma (U-87 MG) mouse model using optical and PET imaging. Finally, accumulation and diffusion into the tumor micro-environment was investigated under microbubble-assisted sonoporation, which helped homogenize the delivery of the micelles. The in vivo experiments showed a good correlation between optical and PET images and demonstrated the stability of the micelles in biological media, their high and long-term retention in the tumors and their clearance through the hepato-biliary pathway. This study demonstrates that bi-modal imaging techniques are powerful tools for the development of new nanocarriers and that sonoporation is a promising method to homogenize nanomedicine delivery to tumors.

Starvation-assisted and photothermal-thriving combined chemo/chemodynamic cancer therapy with PT/MR bimodal imaging.

Chemodynamic therapy (CDT) reflects a novel reactive oxygen species (ROS)-related cancer therapeutic approach. However, CDT monotherapy is often limited by weak efficacy and insufficient endogenous H2O2. Herein, a multifunctional combined bioreactor (MnFe-LDH/MTX@GOx@Ta, MMGT) relying on MnFe-layered double hydroxide (MnFe-LDH) loaded with methotrexate (MTX) and coated with glucose oxidase (GOx)/tannin acid (Ta) is established for applications in H2O2 self-supply and photothermal enhanced chemo/chemodynamic combined therapy along with photothermal (PT) /magnetic resonance (MR) dual-modality imaging ability for cancer treatment. Once internalized into tumor cells, MMGT achieves starvation therapy by catalyzing the oxidation of glucose with GOx, accompanied by the regeneration of H2O2, enabling a Fenton-like reaction to accomplish GOx catalytic amplified CDT. Moreover, MMGT manifests significant tumor-killing ability through improved CDT performance with outstanding photothermal conversion efficiency (η = 52.2%) under 808 nm laser irradiation. In addition, the release of Mn2+ from MnFe-LDH in a solid tumor can significantly enhance T1-contrast MR imaging signals. Combined with MnFe-LDH-induced PT imaging under 808 nm laser irradiation, a dual-modality imaging directed theranostic nanoplatform has been developed. The present study provides a new strategy to design H2O2 self-supply and ROS evolving NIR light-absorption theranostic nanoagent for highly efficient and combined chemo/chemodynamic cancer treatment.

131I labeled pH-responsive gold nanoparticles for bimodal tumor diagnosis

• Preparation of pH-responsive 131 I-labeled gold nano-particle molecular probe. • Aggregation of gold nanoparticles was explored based on the tumor microenvironment. • Dual-modality imaging further improves the diagnostic efficacy of tumors. Considering that each diagnostic method exhibits its disadvantages, such as the poor spatial resolution of SPECT and limited penetration depth of PA imaging, the development of a diagnosis integrated agent with dual-modality imaging performance is of great research interest. Herein, an interesting triggered mechanism, release, and aggregation of radiolabeled Au NPs were explored for tumor diagnosis based on the effect of H + in the tumor microenvironment. In vitro experiments reveal that the pH-responsive Au NPs exhibit an obvious accumulation effect and local surface plasmon resonance (LSPR) coupling effect and generate strong NIR absorption and can be used as the PA imaging agent. Importantly, Au aggregation only appears in the acid tumor microenvironment and displays excellent tumor SPECT diagnostic and photoacoustic imaging performance in vivo. This work provides a new synergistic strategy for SPECT and PA bimodal imaging to further improve the diagnostic efficacy of tumors.

A tumor-targetable probe based on europium(III)/gadolinium(III) complex-conjugated transferrin for dual-modal time-gated luminescence and magnetic resonance imaging of cancerous cells in vitro and in vivo.

The synergy of magnetic resonance imaging (MRI) and time-gated luminescence imaging (TGLI) provides a robust platform with extensive spatial resolution (from submicrometer to hundred-micron) and unlimited penetration depth for visual detection of lesion tissues and target biomolecules. In this work, highly stable lanthanide (Eu3+ and Gd3+) complexes with a terpyridine polyacid ligand, CNSTTA-Ln3+, were chosen as signal reporters for TGLI (Ln3+ = Eu3+) and MRI (Ln3+ = Gd3+), respectively. After conjugating CNSTTA-Ln3+ with a tumor-targetable glycoprotein, transferrin (Tf), the obtained bioconjugate, showed low cytotoxicity and high stability and exhibited strong long-lived luminescence (Tf-CNSTTA-Eu3+, ϕ = 10.8%, τ = 1.27 ms), high magnetic resonance relaxivity (Tf-CNSTTA-Gd3+, r1 = 8.70 mM-1 s-1, r2 = 10.90 mM-1 s-1), and high binding affinity toward Tf receptor-overexpressed cancerous cells. On the basis of these features, a tumor-targetable probe was constructed by simply mixing Tf-CNSTTA-Eu3+ and Tf-CNSTTA-Gd3+, and successfully used for the bimodal TGLI and MRI of tumor cells in tumor-bearing mice. The bimodal imaging simultaneously provided the anatomical and molecular information of the tumor, which enabled the accuracy for tumor diagnosis to be mutually verified, and revealed the potential of Tf-CNSTTA-Gd3+/Eu3+ for the monitoring of cancer cells in vivo.

Iridium Tungstate Nanozyme-Mediated Hypoxic Regulation and Anti-inflammation for Duplex Imaging Guided Photothermal Therapy of Metastatic Breast Tumors.

Metastasis of breast cancer is key to poor prognosis and high mortality. However, the excess reactive oxygen species (ROS) and inflammatory response induced by photothermal therapy (PTT) further aggravate tumor metastasis. Meanwhile, the hypoxic tumor microenvironment promotes tumor cells to metastasize to distant organs. Herein, the intrinsic limitations of PTT for metastatic tumor have been addressed by fabricating polyethylene glycol modified iridium tungstate (IrWOx-PEG) nanoparticles. The as-designed IrWOx-PEG nanoparticles displayed good photothermal (PT) conversion ability for duplex photoacoustic/PT imaging guided PTT and multienzyme mimetic feature for broad-spectrum ROS scavenging. On the one hand, IrWOx-PEG effectively removed excess ROS generated during PTT and reduced inflammation. On the other hand, owing to the catalase-like activity, it preferentially triggered the catalytic production of oxygen by decomposing ROS, leading to relieving of the hypoxic microenvironment. Hence, under bimodal imaging guidance, IrWOx-PEG induced PTT completely eliminated in situ breast cancer in 4T1 tumor-bearing mice with no observable system toxicity, as well as further restricting tumor metastasis to other vital organs (lungs) by ROS scavenging, anti-inflammation, and regulating hypoxic microenvironment. We anticipate that this work will lead to new treatment strategies for other metastatic cancers.

Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure（Au-star@PB）as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging（PAI） and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.

A facile phototheranostic nanoplatform integrating NIR-II fluorescence/PA bimodal imaging and image-guided surgery/PTT combinational therapy for improved antitumor efficacy

Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinational therapy capacity. Herein, the small-molecule cyanine IR780 loaded liposomes have been harnessed as a nanoplatform to simultaneously realize photoacoustic (PA)/the second near-infrared window (NIR-II) fluorescence imaging and image-guided surgery/adjuvant photothermal therapy (PTT). This nanoplatform exhibits attractive properties like uniform controllable size, stable dispersibility, NIR-II fluorescence emission, photothermal conversion, and biocompatibility. Benefiting from the complementary PA/NIR-II fluorescence bimodal imaging, this nanoplatform was successfully applied in precise vasculature delineation and tumor diagnosis. Interestingly, the tumor was clearly detected by NIR-II fluorescence imaging with the highest tumor-to-normal-tissue ratio up to 12.69, while signal interference from the liver was significantly reduced, due to the difference in the elimination rate of the nanoplatform in the liver and tumor. Under the precise guidance of the image, the tumor was accurately resected, and the simulated residual lesion after surgery was completely ablated by adjuvant PTT. This combined therapy showed improved antitumor efficacy over the individual surgery or PTT. This work develops a facile phototheranostic nanoplatform with great significance in accurately diagnosing and effectively treating tumors using simple NIR light irradiation.

Iohexol functionalized Si-Ag:Mn3O4 hybrid nanoparticles based contrast agent for computed tomography imaging

One of the most widely used methods for diagnosing diseases in human tissue is computed tomography (CT). Clinically, CT scans may require contrast media, such as Iohexol, to enhance images of different tissues and organs. However, these iodinized contrast agents have limitations, such as short blood duration, requirement of high-concentration injection, limited enhancement of specific tissues, nonspecific detection, and localization of the substance. Bimodal and multimodal imaging approaches have been used to develop iodinated contrast agents. In this study, silica-Ag:Mn 3 O 4 hybrid nanoparticles were synthesized and conjugated with a commercial iodine contrast agent (Iohexol). Absorption, morphology, and elemental analysis were investigated, followed by a preliminary study on CT contrast enhancement. Compared with Iohexol, the absorption intensity of Iohexol-conjugated nanoparticles (I@Si-Ag:Mn 3 O 4 ) drastically increased, although the loading capacity was estimated to be approximately 40%. The Hounsfield unit (HU) of the nanoparticles increased linearly with increasing mass concentration, exhibiting a stronger HU signal than Iohexol by at least 465 ∆HU at similar concentrations. The maximum CT enhancements were 1644 ± 14 HU for I@Si-Ag:Mn 3 O 4 and 665 ± 14 HU for Iohexol, confirming the CT contrast efficiency of I@Si-Ag:Mn 3 O 4 . These results suggest that the synergy between the nanoparticles and localized Iohexol on the surface-enhanced the performance of the contrast media.

In situ detection of alkaline phosphatase in a cisplatin-induced acute kidney injury model with a fluorescent/photoacoustic bimodal molecular probe.

Kidneys play an important part in drug metabolism and excretion. High local concentration of drugs or drug allergies often cause acute kidney injury (AKI). Identification of effective biomarkers of initial stage AKI and constructing activable molecular probes with excellent detection properties for early evaluation of AKI are necessary, yet remain significant challenges. Alkaline phosphatase (ALP), a key hydrolyzing protease, exists in the epithelial cells of the kidney and is discharged into the urine following kidney injury. However, no studies have revealed its level in drug-induced AKI. Existing ALP fluorescent molecular probes are not suitable for testing and imaging of ALP in the AKI model. Drug-induced AKI is accompanied by oxidative stress, and many studies have indicated that a large increase in reactive oxygen species (ROS) occur in the AKI model. Thus, the probe used for imaging of AKI must be chemically stable in the presence of ROS. However, most existing near-infrared fluorescent (NIRF) ALP probes are not stable in the presence of ROS in the AKI model. Hence, we built a chemically stable molecular sensor (CS-ALP) to map ALP level in cisplatin-induced AKI. This novel probe is not destroyed by ROS generated in the AKI model, thus allowing high-fidelity imaging. In the presence of ALP, the CS-ALP probe generates a new absorbance peak at 685nm and a fluorescent emission peak at 716nm that could be used to "turn on" photoacoustic (PA) and NIRF imaging of ALP in AKI. Levels of CS-ALP build up rapidly in the kidney, and CS-ALP has been successfully applied in NIRF/PA bimodal in vivo imaging. Through the NIRF/PA bimodal imaging results, we demonstrate that upregulated expression of ALP occurs in the early stages of AKI and continues with injury progression.

A Water-Soluble AIEgen for Noninvasive Diagnosis of Kidney Fibrosis via SWIR Fluorescence and Photoacoustic Imaging.

Early diagnosis of renal fibrosis is crucially significant on account of its worldwide prevalent tendency. Optical imaging in the near-infrared window has been recognized as an appealing technique for the timely detection of renal dysfunction. However, formulating a contrast agent that allows early monitoring of renal fibrosis and concurrently renally clearable in a normal group is still challenging. Herein, a nanosized fluorophore with aggregation-induced emission (AIE) features, namely AIE-4PEG550 NPs, is well-tailored and amenable to longitudinal visualization of the fibrosis progression specifically in the early-stage via short-wave infrared (SWIR, 900-1700nm) fluorescence and photoacoustic bimodal imaging. The small size (≈26nm), renally filtrable molecular weight (3.3kDa), high renal clearance efficiency (93.1 ± 1.7% excretion through the kidneys within 24h), outstanding imaging performance, and good biocompatibility, together make AIE-4PEG550 NPs remarkably impressive and far superior to clinical diagnostic assays. The finding in this study would provide a blueprint for the next generation of diagnostic agents for the extent of renal fibrosis.

Recent Advances in Single-Cell Metabolomics Based on Mass Spectrometry

Recent Advances in Single-Cell Metabolomics Based on Mass Spectrometry

Lead/cadmium-free near-infrared multifunctional nanoplatform for deep-tissue bimodal imaging and drug delivery

Well-designed multifunctional nanoplatforms integrating diagnosis and therapy capabilities are of significant importance in the emerging research area of theranostics, which is expected to have great impact on future medicine. Herein, we rationally designed and engineered a multifunctional NaGdF4:Nd3+@mSiO2 nanoplatform by loading ultrasmall NaGdF4:Nd3+ nanoparticles (∼4.1 nm in diameter) into relatively large-channel mesoporous SiO2 (mSiO2) nanospheres for the first time. Thanks to the unique combination of paramagnetic property, and the capability of being excited by near infrared (NIR) light in the first biological window (NIR-I: 700–950 nm) and emitting in the second biological window (NIR-II: 1000–1350 nm) in single-type nanoparticles of NaGdF4:Nd3+, the NaGdF4:Nd3+@mSiO2 nanoplatform realizes magnetic resonance and NIR photoluminescence dual-mode tumor imaging of live mice. In particular, this NIR-I excitation and NIR-II emission property enables in vitro NIR porcine tissue photoluminescence imaging up to 12 mm in thickness. Moreover, the unique three-dimensional mesoporous structure of the nanoplatform allows the efficient loading of doxorubicin molecules (DOX, a commonly used drug model) at a high level and demonstrates pH-responsive drug release behavior that is beneficial for cancer-targeted therapy. More importantly, this NIR-II emitting nanoplatform does not contain toxic heavy metals of lead (Pb) and cadmium (Cd) usually found in NIR-emitting nanoparticles and further, comprises a highly biocompatible, protective SiO2 network. As a result, the NaGdF4:Nd3+@mSiO2 nanoplatform demonstrates much less cytotoxicity, as compared to the counterpart containing Pb and/or Cd-based quantum dots. All these features endow the multifunctional NaGdF4:Nd3+@mSiO2 nanoplatform great potential in simultaneous disease imaging diagnostics and therapeutics.

Microenvironment‐Tailored Catalytic Nanoprobe for Ratiometric NIR‐II Fluorescence/Photoacoustic Imaging of H2O2 in Tumor and Lymphatic Metastasis

AbstractIn vivo H2O2 visualization is crucial for disease diagnosis. Catalytic reaction‐based probes show potential in H2O2 detection, yet their in vivo application remains challenging because catalysts always require a specific pH to function and cellular glutathione (GSH) may suppress signaling by depletion of hydroxyl radicals and oxidized substrates. Here, a microenvironment‐tailored catalytic nanoprobe (MTCN) comprising Fe2+, citric acid (CA), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS), and downconversion nanoparticles in the liposomal cavity as well as a reference dye in the lipid membrane is reported, which utilizes the selective permeability of the liposomal membrane to offer a favorable pH for Fe2+ catalyst with the aid of CA and to avoid GSH‐triggered signal loss by preventing entry of GSH into the cavity. The MTCN displays a large NIR‐II fluorescence (FL) ratio between 1550 and 1080 nm (FL1550Em,808Ex/FL1080Em,980Ex), but a small photoacoustic (PA) ratio between 808 and 1048 nm (PA808/PA1048). Upon exposure of MTCN to H2O2, catalytic conversion of ABTS into its oxidized form ABTS·+ with 808 nm absorption causes a noticeable increment in PA808/PA1048 accompanied by an apparent decrement in FL1550Em,808Ex/FL1080Em,980Ex, enabling bimodal ratiometric imaging of H2O2 in the tumor and lymphatic metastasis.

Multifunctional Polydopamine-Based Nanoparticles for Dual-Mode Imaging Guided Targeted Therapy of Lupus Nephritis.

Lupus nephritis (LN) is a common and refractory inflammation of the kidneys caused by systemic lupus erythematosus. Diagnosis and therapies at this stage are inefficient or have severe side effects. In recent years, nanomedicines show great potential for imaging diagnosis and controlled drug release. Herein, we developed a polydopamine (PDA)-based nanocarrier modified with Fe3O4 and Pt nanoparticles and loaded with necrostatin-1 (Nec-1) for the bimodal imaging and therapy of LN. Results demonstrate that Nec-1/PDA@Pt-Fe3O4 nanocarrier exhibits good biocompatibility. Nec-1, as an inhibitor of receptor-interacting protein 1 kinase, can be used to inhibit receptor-interacting protein 1 kinase activity and then reduces inflammation due to LN. Experiments in vitro and in the LN mouse model confirmed that the nanocarrier can reduce neutrophil extracellular traps (NETs) production by RIPK1 and alleviate the progression of inflammation. Previous studies proved that Pt nanoparticles can catalyze H2O2 to produce oxygen. A blood oxygen graph of mouse photoacoustic tomography confirmed that Nec-1/PDA@Pt-Fe3O4 can generate oxygen to fight against the hypoxic microenvironment of LN. PDA and Fe3O4 are used as photographic developers for photoacoustic or magnetic resonance imaging. The preliminary imaging results support Nec-1/PDA@Pt-Fe3O4 potential for photoacoustic/magnetic resonance dual-mode imaging, which can accurately and non-invasively monitor microscopic changes due to diseases. Nec-1/PDA@Pt-Fe3O4 combining these advantages exhibited outstanding performance in LN imaging and therapy. This work offers valuable insights into LN diagnosis and therapy.

Graphene quantum dots as bimodal imaging agent for X-ray and Computed Tomography

The urgency of new contrast agents, especially for X-ray and Computed Tomography (CT) is increasing each day. Although both imaging modalities are the most routinely used imaging techniques, the availability of contrast agent is very limited. In this scenario, the use of graphene quantum dots (GQDs), a member of the graphene family, which has several characteristics, including low toxicity, good biocompatibility and physical–chemical properties, may represent an important application of this material. Thus, using X-ray (conventional) and CT analysis was evaluated the applicability of GQDs as contrast agent for both imaging modalities. The results demonstrated that GQDs are able to attenuate X-ray forming sharp imaging in both modalities. The data broaden the spectrum of GQDs use.

Bimodal Imaging of Tumors via Genetically Engineered Escherichia coli.

Although there are emerging innovations of molecular imaging probes to detect and image tumors, most of these molecular dyes and nanoparticles have limitations of low targetability in tumors and fast clearance when administered systemically. In contrast, some bacteria, such as Escherichia coli MG1655, can selectively proliferate in a hypoxic environment inside of a tumor for several days, which highlights the potential for the development of a genetically encoded multimodal imaging probe to monitor the progress of the tumor. Here, we developed bimodal imaging tumor-homing bacteria (GVs-miRFP680 MG1655) that allow both optical and acoustic imaging in tumor-bearing mice. An in vivo optical image system and a Vevo 2100 imaging system were applied to detect different imaging properties of the engineered bacteria in vivo. Our results show that the GVs-miRFP680 MG1655 bacteria can effectively integrate the advantages of low tissue absorbance from near-infrared fluorescent proteins and non-invasiveness from gas vesicles. We successfully developed GVs-miRFP680 MG1655 bacteria, which have both acoustic and optical imaging abilities in vitro and in vivo. The acoustic signal can last for up to 25 min, while the near-infrared fluorescence signal can last for up to 96 h. The combination of different imaging modalities in the tumor-homing bacteria may contribute to the non-invasive monitoring of the therapeutic effect of bacterial therapy in the future.

Tumor-Targeting NIRF/MR Dual-Modal Molecular Imaging Probe for Surgery Navigation.

Multimodality imaging recognized as a promising monitoring strategy can serve the needs of accurate diagnosis and treatment of cancer by providing molecular and anatomic information about tumor sites. However, the probes based on multiple imaging modalities for surgery navigation remain limited due to poor biocompatibility and tumor targeting specificity. Herein, we present a small-molecule near-infrared fluorescence/magnetic resonance (NIRF/MR) imaging probe, Gd-NMC-3, covalently coupled with DCDSTCY and Gd-DOTA via butane diamine, for precise detection and intraoperative visualization. The in vitro and in vivo studies demonstrated that Gd-NMC-3 could be effectively accumulated in tumor sites as a bimodal imaging molecule exhibiting significant fluorescence accumulation and reasonable relaxation property in tumors with low cytotoxicity and good biocompatibility. Furthermore, Gd-NMC-3 was successfully applied to provide real-time visual navigation in LM3 orthotopic and subcutaneous tumor models to guide the resection of tumors. Importantly, no more fluorescence was observed in mice after operation, implying the total removal of tumor tissues. In conclusion, Gd-NMC-3 has great potential to be applied in the clinic based on its high resolution and sensitivity in tumor imaging.

Multifunctional Magnetic CuS/Gd2O3 Nanoparticles for Fluorescence/Magnetic Resonance Bimodal Imaging-Guided Photothermal-Intensified Chemodynamic Synergetic Therapy of Targeted Tumors.

Chemodynamic therapy (CDT), which consumes endogenous hydrogen peroxide (H2O2) to generate reactive oxygen species (ROS) and causes oxidative damage to tumor cells, shows tremendous promise for advanced cancer treatment. However, the rate of ROS generation based on the Fenton reaction is prone to being restricted by inadequate H2O2 and unattainable acidity in the hypoxic tumor microenvironment. We herein report a multifunctional nanoprobe (BCGCR) integrating bimodal imaging and photothermal-enhanced CDT of the targeted tumor, which is produced by covalent conjugation of bovine serum albumin-stabilized CuS/Gd2O3 nanoparticles (NPs) with the Cy5.5 fluorophore and the tumor-targeting ligand RGD. BCGCR exhibits intense near-infrared (NIR) fluorescence and acceptable r1 relaxivity (∼15.3 mM-1 s-1) for both sensitive fluorescence imaging and high-spatial-resolution magnetic resonance imaging of tumors in living mice. Moreover, owing to the strong NIR absorbance from the internal CuS NPs, BCGCR can generate localized heat and displays a high photothermal conversion efficiency (30.3%) under 980 nm laser irradiation, which enables photothermal therapy and further intensifies ROS generation arising from the Cu-induced Fenton-like reaction for enhanced CDT. This synergetic effect shows such an excellent therapeutic efficacy that it can ablate xenografted tumors in vivo. We believe that this strategy will be beneficial to exploring other advanced nanomaterials for the clinical application of multimodal imaging-guided synergetic cancer therapies.

Multifunctional probe based on modified Ag&Mn:ZnInS QDs for dual-mode fluorescence and magnetic resonance imaging of intracellular glutathione

Glutathione (GSH) plays vital roles in a variety of biological processes, and the development of simple and effective GSH detection method is an important research topic. Herein, a multifunctional probe based on Ag&Mn:ZnInS quantum dots (QDs) was developed for bimodal imaging of GSH. MnO2, as an efficient fluorescence quencher, was in-situ grown on the surface of QDs, and then modified with hyaluronic acid (HA) to improve the stability and targeted recognition capability of the probe due to the binding between HA and CD44 receptors. After MnO2 was deconstructed by GSH, the fluorescence of the probe was recovered and the generated Mn2+ could serve as good magnetic resonance imaging (MRI) contrast agent. Moreover, the near-infrared emission probe was successfully employed in living cell and zebrafish imaging due to its low toxicity and high anti-biological interference performance. This strategy provides a simple dual-mode fluorescence/MRI imaging of GSH, which may have a broad application in biological detection.

A Multifunctional Nanoplatform Based on Graphene Quantum Dots‐Cobalt Ferrite for Monitoring of Drug Delivery and Fluorescence/Magnetic Resonance Bimodal Cellular Imaging

A novel multifunctional nanoplatform based on graphene quantum dots (GQDs)‐cobalt ferrite (CoFe2O4) is demonstrated for monitoring of the drug delivery and fluorescence/magnetic resonance imaging (MRI) bimodal cellular imaging. The nanoplatform is fabricated by assembling the GQDs onto the surface of magnetic CoFe2O4@SiO2 (CFO@SiO2) via covalent binding, subsequently conjugated with folic acid (FA). Then anticancer drug doxorubicin (DOX) is loaded on the GQD‐CFO/SiO2/FA with a capacity of 65.4 wt%. The DOX/GQD‐CFO@SiO2/FA can be used for monitoring of drug release by detecting the Förster resonant energy transfer (FRET) signals, with the GQDs serve as the drug carrier and the donor in FRET model. Herein, the monitoring of drug delivery is explored via the corresponding changes in FRET. The reduced brightness of T2‐weighted MRI images indicates the potential of GQD‐CFO@SiO2/FA to be applied as the negative contrast agent. The fluorescence/MRI bimodal cellular imaging can facilitate the transportation of drug delivery. Furthermore, the cytotoxicity assay confirms the desirable biocompatibility of GQD‐CFO@SiO2/FA nanoplatform, and DOX/GQD‐CFO@SiO2/FA exhibits notable cytotoxicity to HeLa cells. These results demonstrate the significantly increased therapeutic efficiency of this nanoplatform. Thus, the novel GQD‐CFO@SiO2/FA can be a promising multifunctional nanoplatform with monitoring of drug delivery and fluorescence/MRI bimodal cellular imaging.