Dotted Core–Shell Nanoparticles for T1‐Weighted MRI of Tumors

Gd‐based T ₁‐weighted contrast agents have dominated the magnetic resonance imaging (MRI) contrast agent market for decades. Nevertheless, they are reported to be nephrotoxic and the U.S. Food and Drug Administration has issued a general warning concerning their use. In order to reduce the risk of nephrotoxicity, the MRI performance of the Gd‐based T ₁‐weighted contrast agents needs to be improved to allow a much lower dosage. In this study, novel dotted core–shell nanoparticles (FeGd‐HN3‐RGD2) with superhigh r ₁ value (70.0 mM^?1 s^?1) and very low r ₂/r ₁ ratio (1.98) are developed for high‐contrast T ₁‐weighted MRI of tumors. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and histological analyses show good biocompatibility of FeGd‐HN3‐RGD2. Laser scanning confocal microscopy images and flow cytometry demonstrate active targeting to integrin α_vβ₃ positive tumors. MRI of tumors shows high tumor ΔSNR for FeGd‐HN3‐RGD2 (477 ± 44%), which is about 6‐7‐fold higher than that of Magnevist (75 ± 11%). MRI and inductively coupled plasma results further confirm that the accumulation of FeGd‐HN3‐RGD2 in tumors is higher than liver and spleen due to the RGD2 targeting and small hydrodynamic particle size (8.5 nm), and FeGd‐HN3‐RGD2 is readily cleared from the body by renal excretion.     

Ten‐Gram‐Scale Facile Synthesis of Organogadolinium Complex Nanoparticles for Tumor Diagnosis

The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T₁ contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten‐gram‐scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd‐salicylate nanoparticles, GdSalNPs‐rBSA) with high r₁ value of 19.51 mm ^?1 s^?1 and very low r₂/r₁ ratio of 1.21 (B₀ = 1.5 T) for high‐contrast T₁‐weighted MRI of tumors. The GdSalNPs‐rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t_1/2 = 6.13 h), almost no Gd³⁺ release, and excellent biosafety. Moreover, the GdSalNPs‐rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal‐to‐noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis.     

Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non‐specificity, and low r₁) that limit their applications. Herein, a wet‐chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES‐GON‐PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T₁‐weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r₁ = 70.2 ± 1.8 mM^?1 s^?1, and r₂/r₁ = 1.02 ± 0.03, at 1.5 T). The r₁ is much higher and the r₂/r₁ is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES‐GON‐PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES‐GON‐PAA@RGD2) for T₁‐weighted MRI of tumors that overexpress RGD receptors (i.e., integrin α_vβ₃). The maximum signal enhancement (ΔSNR) for T₁‐weighted MRI of tumors reaches up to 372 ± 56% at 2 h post‐injection of ES‐GON‐PAA@RGD2, which is much higher than commercial Gd‐chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES‐GON‐PAA@RGD2 with remarkable relaxivities is a promising and powerful T₁‐weighted MRI contrast agent.     

Detection of β‐Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease

The accumulation and formation of β‐amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP‐BSA_x‐Sia) to overcome the challenges in Aβ imaging in vivo. The NP‐BSA_x‐Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP‐BSA_x‐Sia binds with Aβ in a sialic acid dependent manner with high selectivities toward Aβ deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aβ in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T₂*‐weighted MRI shows that Aβ plaques in mouse brains can be detected as aided by NP‐BSA_x‐Sia, which is confirmed by histological analysis. Thus, NP‐BSA_x‐Sia is a promising new tool for noninvasive in vivo detection of Aβ plaques.     

FeIII‐Doped Two‐Dimensional C3N4 Nanofusiform: A New O2‐Evolving and Mitochondria‐Targeting Photodynamic Agent for MRI and Enhanced Antitumor Therapy

Local hypoxia in tumors, as well as the short lifetime and limited action region of ¹O₂, are undesirable impediments for photodynamic therapy (PDT), leading to a greatly reduced effectiveness. To overcome these adversities, a mitochondria‐targeting, H₂O₂‐activatable, and O₂‐evolving PDT nanoplatform is developed based on Fe^III‐doped two‐dimensional C₃N₄ nanofusiform for highly selective and efficient cancer treatment. The ultrahigh surface area of 2D nanosheets enhances the photosensitizer (PS) loading capacity and the doping of Fe^III leads to peroxidase mimetics with excellent catalytic performance towards H₂O₂ in cancer cells to generate O₂. As such tumor hypoxia can be overcome and the PDT efficacy is improved, whilst at the same time endowing the PDT theranostic agent with an effective T ₁‐weighted in vivo magnetic resonance imaging (MRI) ability. Conjugation with a mitochondria‐targeting agent could further increase the sensitivity of cancer cells to ¹O₂ by enhanced mitochondria dysfunction. In vitro and in vivo anticancer studies demonstrate an outstanding therapeutic effectiveness of the developed PDT agent, leading to almost complete destruction of mouse cervical tumor. This development offers an attractive theranostic agent for in vivo MRI and synergistic photodynamic therapy toward clinical applications.     

Fluorescent Magnetic Fe3O4/Rare Earth Colloidal Nanoparticles for Dual‐Modality Imaging

Fluorescent magnetic colloidal nanoparticles (FMCNPs) are produced by a two‐step, seed emulsifier‐free emulsion polymerization in the presence of oleic acid and sodium undecylenate‐modified Fe₃O₄ nanoparticles (NPs). The Fe₃O₄/poly(St‐co‐GMA) nanoparticles are first synthesized as the seed and Eu(AA)₃Phen is copolymerized with the remaining St and GMA to form the fluorescent polymer shell in the second step. The uniform core–shell structured FMCNPs with a mean diameter of 120 nm exhibit superparamagnetism with saturation magnetization of 1.92 emu/g. Red luminescence from the FMCNPs is confirmed by the salient fluorescence emission peaks of europium ions at 594 and 619 nm as well as 2‐photon confocal scanning laser microscopy. The in vitro cytotoxicity test conducted using the MTT assay shows good cytocompatibility and the T₂ relaxivity of the FMCNPs is 353.86 mM^?1S^?1 suggesting its potential in magnetic resonance imaging (MRI). In vivo MRI studies based on a rat model show significantly enhanced T₂‐weighted images of the liver after administration and prussian blue staining of the liver tissue slice reveals accumulation of FMCNPs in the organ. The cytocompatibility, superparamagnetism, and excellent fluorescent properties of FMCNPs make them suitable for biological imaging probes in MRI and optical imaging.     

Multifunctional Yolk‐in‐Shell Nanoparticles for pH‐triggered Drug Release and Imaging

Multifunctional nanoparticles are synthesized for both pH‐triggered drug release and imaging with radioluminescence, upconversion luminescent, and magnetic resonance imaging (MRI). The particles have a yolk‐in‐shell morphology, with a radioluminescent core, an upconverting shell, and a hollow region between the core and shell for loading drugs. They are synthesized by controlled encapsulation of a radioluminescent nanophosphor yolk in a silica shell, partial etching of the yolk in acid, and encapsulation of the silica with an upconverting luminescent shell. Metroxantrone, a chemotherapy drug, was loaded into the hollow space between X‐ray phosphor yolk and up‐conversion phosphor shell through pores in the shell. To encapsulate the drug and control the release rate, the nanoparticles are coated with pH‐responsive biocompatible polyelectrolyte layers of charged hyaluronic acid sodium salt and chitosan. The nanophosphors display bright luminescence under X‐ray, blue light (480 nm), and near infrared light (980 nm). They also served as T₁ and T₂ MRI contrast agents with relaxivities of 3.5 mM^?1 s^?1 (r₁) and 64 mM^?1s^?1 (r₂). These multifunctional nanocapsules have applications in controlled drug delivery and multimodal imaging.     

Core–Satellite Polydopamine–Gadolinium‐Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging‐guided therapy. However, most gadolinium (Gd)–chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released‐Gd‐ions‐associated toxicity. Herein, a radionuclide‐⁶⁴Cu‐labeled doxorubicin‐loaded polydopamine (PDA)–gadolinium‐metallofullerene core–satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging‐guided combination cancer therapy. In this system, the near‐infrared (NIR)‐absorbing PDA acts as a platform for the assembly of different moieties; Gd₃N@C₈₀, a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as‐prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r ₁ = 14.06 mM^?1 s^?1), low risk of release of Gd ions, and NIR‐triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo‐photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.     

Superparamagnetic cobalt ferrite nanoparticles as T 2 contrast agent in MRI: in vitro study

Superparamagnetic cobalt ferrite nanoparticles (CoFe₂ O₄) possess favourite advantages for theranostic applications. Most of previous studies reported that CoFe₂ O₄ magnetic nanoparticles (MNPs) are suitable candidates for induction of hyperthermia and transfection agents for drug delivery. The present study synthesized and investigated the potential use of CoFe₂ O₄ as a contrast agent in magnetic resonance imaging (MRI) by using a conventional MRI system. The CoFe₂ O₄ were synthesized using co‐precipitation method and characterized by TEM, XRD, FTIR, EDX and VSM techniques. Relaxivities r ₁ and r ₂ of CoFe₂ O₄ were then calculated using a 1.5 Tesla clinical magnetic field. The cytotoxicity of CoFe₂ O₄ was evaluated by the MTT assay. Finally, the optimal concentrations of MNPs for MRI uses were calculated through the analysis of T ₂ weighted imaging cell phantoms. The superparamagnetic CoFe2O4 NPs with an average stable size of 10.45 nm were synthesized. Relaxivity r ₁, ₂ calculations resulted in suitable r ₂ and r ₂ / r ₁ with values of 58.6 and 51 that confirmed the size dependency on relaxivity values. The optimal concentration of MNPs for MR image acquisition was calculated as 0.154 mM. Conclusion: CoFe₂ O₄ synthesized in this study could be considered as a suitable T ₂ weighted contrast agent because of its high r ₂ /r ₁ value.Inspec keywords: nanoparticles, phantoms, transmission electron microscopy, superparamagnetism, ferrites, cellular biophysics, precipitation (physical chemistry), magnetisation, cobalt compounds, nanomagnetics, magnetic particles, nanofabrication, biomedical MRI, nanomedicine, X‐ray diffraction, Fourier transform infrared spectra, X‐ray chemical analysis, particle size, medical image processingOther keywords: superparamagnetic cobalt ferrite nanoparticles, T₂ contrast agent, MRI, in vitro study, magnetic resonance imaging, coprecipitation method, transmission electron microscopy, X‐ray diffraction, Fourier‐transform IR spectra, energy dispersive X‐ray analysis, vibrating sample magnetometer, clinical magnetic field, cytotoxicity, MTT assay, T₂ weighted imaging cell phantoms, T₂ weighted contrast agent, stable size, size dependency, relaxivity values, MR image acquisition, magnetic flux density 1.5 T, CoFe₂ O₄      

In Vivo Tumor Visualization through MRI Off‐On Switching of NaGdF4–CaCO3 Nanoconjugates

The development of high‐performance contrast agents in magnetic resonance imaging (MRI) has recently received considerable attention, as they hold great promise and potential as a powerful tool for cancer diagnosis. Despite substantial achievements, it remains challenging to develop nanostructure‐based biocompatible platforms that can generate on‐demand MRI signals with high signal‐to‐noise ratios and good tumor specificity. Here, the design and synthesis of a new class of nanoparticle‐based contrast agents comprising self‐assembled NaGdF₄ and CaCO₃ nanoconjugates is reported. In this design, the spatial confinement of the T₁ source (Gd³⁺ ions) leads to an “OFF” MRI signal due to insufficient interaction between the protons and the crystal lattices. However, when immersed in the mildly acidic tumor microenvironment, the embedded CaCO₃ nanoparticles generate CO₂ bubbles and subsequently disconnect the nanoconjugate, thus resulting in an “ON” MRI signal. The in vivo performance of these nanoconjugates shows more than 60‐fold contrast enhancement in tumor visualization relative to the commercially used contrast agent Magnevist. This work presents a significant advance in the construction of smart MRI nanoprobes ideally suited for deep‐tissue imaging and target‐specific cancer diagnosis.     

Manganese‐Based Layered Double Hydroxide Nanoparticles as a T1‐MRI Contrast Agent with Ultrasensitive pH Response and High Relaxivity

Recently, Mn(II)‐containing nanoparticles have been explored widely as an attractive alternative to Gd(III)‐based T₁‐weighted magnetic resonance imaging (MRI) contrast agents (CAs) for cancer diagnosis. However, as far as it is known, no Mn‐based MRI CAs have been reported to sensitively respond to a very weakly acidic environment (pH 6.5–7.0, i.e., the pH range in a tumor microenvironment) with satisfactory imaging performance. Here, recently devised pH‐ultrasensitive Mn‐based layered double hydroxide (Mn‐LDH) nanoparticles with superb longitudinal relaxivity (9.48 mm ^?1 s^?1 at pH 5.0 and 6.82 mm ^?1 s^?1 at pH 7.0 vs 1.16 mm ^?1 s^?1 at pH 7.4) are reported, which may result from the unique microstructure of Mn ions in Mn‐LDH, as demonstrated by extended X‐ray absorption fine structure. Further in vivo imaging reveals that Mn‐LDH nanoparticles show clear MR imaging for tumor tissues in mice for 2 d post intravenous injection. Thus, this novel Mn‐doped LDH nanomaterial, together with already demonstrated capacity for drug and gene delivery, is a very potential theranostic agent for cancer diagnosis and treatment.     

Multifunctional Magnetic Gd3+‐Based Coordination Polymer Nanoparticles: Combination of Magnetic Resonance and Multispectral Optoacoustic Detections for Tumor‐Targeted Imaging in vivo

To overcome traditional barriers in optical imaging and microscopy, optoacoustic‐imaging has been changed to combine the accuracy of spectroscopy with the depth resolution of ultrasound, achieving a novel modality with powerful in vivo imaging. However, magnetic resonance imaging provides better spatial and anatomical resolution. Thus, a single hybrid nanoprobe that allows for simultaneous multimodal imaging is significant not only for cutting edge research in imaging science, but also for accurate clinical diagnosis. A core‐shell‐structured coordination polymer composite microsphere has been designed for in vivo multimodality imaging. It consists of a Fe₃O₄ nanocluster core, a carbon sandwiched layer, and a carbocyanine‐Gd^III (Cy‐Gd^III) coordination polymer outer shell (Fe₃O₄@C@Cy‐Gd^III). Folic acid‐conjugated poly(ethylene glycol) chains are embedded within the coordination polymer shell to achieve extended circulation and targeted delivery of probe particles in vivo. Control of Fe₃O₄ core grain sizes results in optimal r₂ relaxivity (224.5 × 10^–3 m ⁻¹ s^‐1) for T₂‐weighted magnetic resonance imaging. Cy‐Gd^III coordination polymers are also regulated to obtain a maximum 25.1% of Cy ligands and 5.2% of Gd^III ions for near‐infrared fluorescence and T₁‐weighted magnetic resonance imaging, respectively. The results demonstrate their impressive abilities for targeted, multimodal, and reliable imaging.     

All‐Solution‐Processed Pure Formamidinium‐Based Perovskite Light‐Emitting Diodes

All‐solution‐processed pure formamidinium‐based perovskite light‐emitting diodes (PeLEDs) with record performance are successfully realized. It is found that the FAPbBr₃ device is hole dominant. To achieve charge carrier balance, on the anode side, PEDOT:PSS 8000 is employed as the hole injection layer, replacing PEDOT:PSS 4083 to suppress the hole current. On the cathode side, the solution‐processed ZnO nanoparticle (NP) is used as the electron injection layer in regular PeLEDs to improve the electron current. With the smallest ZnO NPs (2.9 nm) as electron injection layer (EIL), the solution‐processed PeLED exhibits a highest forward viewing power efficiency of 22.3 lm W^?1, a peak current efficiency of 21.3 cd A^?1, and an external quantum efficiency of 4.66%. The maximum brightness reaches a record 1.09 × 10⁵ cd m^?2. A record lifetime T₅₀ of 436 s is achieved at the initial brightness of 10 000 cd m^?2. Not only do PEDOT:PSS 8000 HIL and ZnO NPs EIL modulate the injected charge carriers to reach charge balance, but also they prevent the exciton quenching at the interface between the charge injection layer and the light emission layer. The subbandgap turn‐on voltage is attributed to Auger‐assisted energy up‐conversion process.     

Hollow manganese phosphate nanoparticles as smart multifunctional probes for cancer cell targeted magnetic resonance imaging and drug delivery

Multifunctional probes for simultaneous magnetic resonance imaging (MRI) and drug delivery have attracted considerable interest due to their promising potential applications in the early-stage diagnosis and therapy of the diseases. In this study, hollow manganese phosphate nanoparticles (HMP NPs) with an average diameter of 18 nm were synthesized and aminated through silanization, which enabled the covalent conjugation of biocompatible poly(ethylene glycol) (PEG) on their surfaces. The anti-tumor drug doxorubicin (DOX) could be loaded into the hollow cavities. Under physiological conditions (pH 7.4), the NPs showed low MRI T ₁ contrast (r ₁ = 1.19 L·mmol^?1·s^?1), whereas high T ₁ enhancement (r ₁ = 5.22 L·mmol^?1·s^?1) was achieved after dissolving them in endosome/lysosome mimetic conditions (pH 5.4). This is due to the fact that the NPs were easily eroded, which resulted in the release of Mn²⁺ at low pH. To use this interesting phenomenon for targeted DOX drug delivery, we conjugated the tumor-targeting ligand folic acid (FA) on HMP NPs and investigated their drug delivery capacity and cytotoxicity to cell lines expressing different amount of folate receptor (FR). KB cells showed more significant cellular uptake than HeLa cells and A549 cells, as confirmed by confocal laser scanning microscopy (CLSM), flow cytometry and cellular T ₁-weighted MRI. Furthermore, the drug-loaded HMP NPs exhibited greater cytotoxicity to KB cells. Our results suggest that functionalized HMP NPs can act as an effective multifunctional probe for selective diagnosis with MRI, as well as giving efficient targeted drug delivery.      

Monitoring of Time‐Between‐Events with a Generalized Group Runs Control Chart

Control charting methods for time between events (TBE) is important in both manufacturing and nonmanufacturing fields. With the aim to enhance the speed for detecting shifts in the mean TBE, this paper proposes a generalized group runs TBE chart to monitor the mean TBE of a homogenous Poisson failure process. The proposed chart combines a TBE subchart and a generalized group conforming run length subchart. The zero‐state and steady‐state performances of the proposed chart were evaluated by applying a Markov chain method. Overall, it is found that the proposed chart outperforms the existing TBE charts, such as the T, T_r, EWMA‐T, Synth‐T_r, and GR‐T_r charts. Copyright © 2015 John Wiley & Sons, Ltd.     

A Self‐Assembled Biocompatible Nanoplatform for Multimodal MR/Fluorescence Imaging Assisted Photothermal Therapy and Prognosis Analysis

The need for better imaging assisted cancer therapy calls for new biocompatible agents with excellent imaging and therapeutic capabilities. This study successfully fabricates albumin‐cooperated human serum albumin (HSA)‐GGD‐ICG nanoparticles (NPs), which are comprised of a magnetic resonance (MR) contrast agent, glycyrrhetinic‐acid‐modified gadolinium (III)‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetate (GGD), and a fluorescence (FL) dye, indocyanine green (ICG), for multimodal MR/FL imaging assisted cancer therapy. These HSA‐GGD‐ICG NPs with excellent biocompatibility are stable under physiological conditions, and exhibit enhanced T₁ contrast capability and improved fluorescence imaging capacity. In vitro experiments reveal an apparent effect of the NPs in killing tumor cells under low laser irradiation, due to the enhanced photothermal conversion efficiency (≈85.1%). Importantly, multimodal MR/FL imaging clearly shows the in vivo behaviors and the efficiency of tumor accumulation of HSA‐GGD‐ICG NPs, as confirmed by a pharmacokinetic study. With the guidance of multimodal imaging, photothermal therapy is subsequently conducted, which demonstrates again high photothermal conversion capability for eliminating tumors without relapse. Notably, real‐time monitoring of tumor ablation for prognosis and therapy evaluation is also achieved by MR imaging. This strategy of constructing nanoplatforms through albumin‐mediated methods is both convenient and efficient, which would enlighten the design of multimodal imaging assisted cancer therapy for potential clinical translation.     

Polycatechol Nanoparticle MRI Contrast Agents

Amphiphilic triblock copolymers containing Fe^III‐catecholate complexes formulated as spherical‐ or cylindrical‐shaped micellar nanoparticles ( SMN and CMN , respectively) are described as new T ₁‐weighted agents with high relaxivity, low cytotoxicity, and long‐term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape‐dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN . These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle‐based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium‐free, safe, and effective imaging agents for MRI contrast enhancement.     

DNA‐Assembled Core‐Satellite Upconverting‐Metal–Organic Framework Nanoparticle Superstructures for Efficient Photodynamic Therapy

DNA‐mediated assembly of core–satellite structures composed of Zr(IV)‐based porphyrinic metal‐organic framework (MOF) and NaYF₄,Yb,Er upconverting nanoparticles (UCNPs) for photodynamic therapy (PDT) is reported. MOF NPs generate singlet oxygen (¹O₂) upon photoirradiation with visible light without the need for additional small molecule, diffusional photosensitizers such as porphyrins. Using DNA as a templating agent, well‐defined MOF–UCNP clusters are produced where UCNPs are spatially organized around a centrally located MOF NP. Under NIR irradiation, visible light emitted from the UCNPs is absorbed by the core MOF NP to produce ¹O₂ at significantly greater amounts than what can be produced from simply mixing UCNPs and MOF NPs. The MOF–UCNP core–satellite superstructures also induce strong cell cytotoxicity against cancer cells, which are further enhanced by attaching epidermal growth factor receptor targeting affibodies to the PDT clusters, highlighting their promise as theranostic photodynamic agents.     

DNA‐Driven Two‐Layer Core–Satellite Gold Nanostructures for Ultrasensitive MicroRNA Detection in Living Cells

It is a significant challenge to achieve controllable self‐assembly of superstructures for biological applications in living cells. Here, a two‐layer core–satellite assembly is driven by a Y‐DNA, which is designed with three nucleotide chains that hybridized through complementary sequences. The two‐layer core–satellite nanostructure (C₃₀S₅S₁₀ NS) is constructed using 30 nm gold nanoparticles (Au NPs) as the core, 5 nm Au NPs as the first satellite layer, and 10 nm Au NPs as the second satellite layer, resulting in a very strong circular dichroism (CD) and surface‐enhanced Raman scattering. After optimization, the yield is up to 85%, and produces a g‐factor of 0.16 × 10^?2. The hybridization of the target microRNA (miRNA) with the molecular probe causes a significant drop in the CD and Raman signals, and this phenomenon is used to detect the miRNA in living cells. The CD signal has a good linear range of 0.011–20.94 amol ng_RNA^?1 and a limit of detection (LOD) of 0.0051 amol ng_RNA^?1, while Raman signal with the range of 0.052–34.98 amol ng_RNA^?1 and an LOD of 2.81 × 10^?2 amol ng_RNA^?1. This innovative dual‐signal method can be used to quantify biomolecules in living cells, opening the way for ultrasensitive, highly accurate, and reliable diagnoses of clinical diseases.     

A Magnetofluorescent Carbon Dot Assembly as an Acidic H2O2‐Driven Oxygenerator to Regulate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy

Recent studies indicate that carbon dots (CDs) can efficiently generate singlet oxygen (¹O₂) for photodynamic therapy (PDT) of cancer. However, the hypoxic tumor microenvironment and rapid consumption of oxygen in the PDT process will severely limit therapeutic effects of CDs due to the oxygen‐dependent PDT. Thus, it is becoming particularly important to develop a novel CD as an in situ tumor oxygenerator for overcoming hypoxia and substantially enhancing the PDT efficacy. Herein, for the first time, magnetofluorescent Mn‐CDs are successfully prepared using manganese(II) phthalocyanine as a precursor. After cooperative self‐assembly with DSPE‐PEG, the obtained Mn‐CD assembly can be applied as a smart contrast agent for both near‐infrared fluorescence (FL) (maximum peak at 745 nm) and T₁‐weighted magnetic resonance (MR) (relaxivity value of 6.97 mM^?1 s^?1) imaging. More interestingly, the Mn‐CD assembly can not only effectively produce ¹O₂ (quantum yield of 0.40) but also highly catalyze H₂O₂ to generate oxygen. These collective properties of the Mn‐CD assembly enable it to be utilized as an acidic H₂O₂‐driven oxygenerator to increase the oxygen concentration in hypoxic solid tumors for simultaneous bimodal FL/MR imaging and enhanced PDT. This work explores a new biomedical use of CDs and provides a versatile carbon nanomaterial candidate for multifunctional nanotheranostic applications.