A responsive nanoplatform with molecular and structural imaging capacity for assisting accurate diagnosis of early rheumatoid arthritis.

Accurate early diagnosis of rheumatoid arthritis (RA) and prompt implementation of appropriate treatment approaches are crucial. In the clinic, magnetic resonance imaging (MRI) has been recommended for implementation to aid in the precise and early diagnosis of RA. However, they are still limited by issues regarding specificity and their ability to capture comprehensive information about the pathological features. Herein, a responsive multifunctional nanoplatform with targeting capabilities (hMnO2-IR@BSA-PEG-FA) is constructed through integrating a RA microenvironment-responsive MRI contrast agent with activatable near-infrared (NIR) fluorescence imaging, aiming to simultaneously acquire comprehensive pathological features of RA from both structural and molecular imaging perspectives. Moreover, taking advantage of its targeting function to synovial microphages, hMnO2-IR@BSA-PEG-FA demonstrated a remarkable capability to accumulate effectively at the synovial tissue. Additionally, hMnO2 responded to the mild acidity and reactive oxygen species (ROS) in the RA microenvironment, leading to the controlled release of Mn2+ ions and IR780, which separately caused special MRI contrast enhancement of synovial tissues and sensitively demonstrated the presence of ROS and weakly acid microenvironment by NIR imaging. Consequently, hMnO2-IR@BSA-PEG-FA is expected to serve as a promising nanoplatform, offering valuable assistance in the precise diagnosis of early-stage RA by specially providing comprehensive information about the pathological features.

Naturally biocompatible melanin based iron-complex nanoparticles for pH-responsive magnetic resonance imaging.

The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on ther1of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM-1s-1at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effectin vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.

Donor-Acceptor Engineering for Tailoring Highly Efficient Photosensitizers for Image-Guided Antitumor Photodynamic Therapy.

Photosensitizers (PSs) have greatly flourished as a promising tool for photodynamic therapy owing to their integration of both in situ diagnosis and treatment in a single nanoplatform. However, there is still a need to explore synthesis pathways that can result in high-performance PSs with good reproducibility, high yield, less dark toxicity, and an attractive therapeutic index. Therefore, by exploiting the precise molecular engineering guideline, this work unveils a straightforward protocol to fabricate three homologous PSs (TPA-T-RS, TPA-Ts-RS, and TPA-Ts-RCN) with aggregation-induced emission (AIE) characteristics. Through slight structural tuning, the PSs are capable of anchoring to the cell membrane, mitochondria, and lysosome, and effectively generating reactive oxygen species (ROS). More importantly, TPA-Ts-RCN proved an intuitively appealing imaging-guided photodynamic therapy (PDT) effect. This work is expected to add a promising dimension to the field of architecting AIE PSs for image-guided photodynamic therapy.

Hypoxia-Responsive T2-to-T1 Dynamically Switchable Extremely Small Iron Oxide Nanoparticles for Sensitive Tumor Imaging In Vivo.

To realize the accurate diagnosis of tumors by magnetic resonance imaging (MRI), switchable magnetic resonance contrast agents (CAs) between T1 and T2 contrast enhancement that are constructed based on extremely small iron oxide nanoparticles (ESIONPs) have been developed in recent years. We herein report, for the first time, a novel ESIONP-based nanocluster (named EAmP), which exhibited hypoxia responsiveness to the tumor microenvironment and offered a T2-to-T1-switchable contrast enhancement function, effectively distinguishing between the normal tissue and tumor tissue. In detail, active perfluorophenyl ester-modified ESIONPs with a diameter of approximately 3.6 nm were initially synthesized, and then 4,4'-azodianiline was used as a cross-linker to facilitate the formation of nanoclusters from ESIONPs through the reaction between the active ester and amine. Finally, poly(ethylene glycol) was further modified onto nanoclusters by utilizing the remaining active ester residues. The resulting EAmP demonstrated satisfactory colloidal stability and favorable biosafety and exhibited a desired T2-to-T1-switchable function, as evidenced by conversion from nanocluster to the dispersed state and a significant decrease in the r2/r1 ratio from 14.86 to 1.61 when exposed to a mimical hypoxic environment in the solution. Moreover, EAmP could decompose into dispersed ESIONPs at the tumor region, resulting in a switch from T2 to T1 contrast enhancement. This T2-to-T1-switchable contrast agent offers high sensitivity and signal-to-noise ratio to realize the accurate diagnosis of tumors. In conclusion, hypoxia-responsive EAmP is a potential MRI nanoprobe for improving the diagnostic accuracy of solid tumors.

Research development of porphyrin-based metal-organic frameworks: targeting modalities and cancer therapeutic applications.

Porphyrins are naturally occurring organic molecules that have attracted widespread attention for their potential in the field of biomedical research. Porphyrin-based metal-organic frameworks (MOFs) that utilize porphyrin molecules as organic ligands have gained attention from researchers due to their excellent results as photosensitizers in tumor photodynamic therapy (PDT). Additionally, MOFs hold significant promise and potential for other tumor therapeutic approaches due to their tunable size and pore size, excellent porosity, and ultra-high specific surface area. Active delivery of nanomaterials via targeted molecules for tumor therapy has demonstrated greater accumulation, lower drug doses, higher therapeutic efficacy, and reduced side effects relative to passive targeting through the enhanced permeation and retention effect (EPR). This paper presents a comprehensive review of the targeting methods employed by porphyrin-based MOFs in tumor targeting therapy over the past few years. It further discusses the applications of porphyrin-based MOFs for targeted cancer therapy through various therapeutic methods. The objective of this paper is to provide a valuable reference and source of ideas for targeted therapy using porphyrin-based MOF materials and to inspire further exploration of their potential in the field of cancer therapy.

A tumor-targeting and ROS-responsive iron-based T1 magnetic resonance imaging contrast agent for highly specific tumor imaging.

T1 contrast agents (CAs) exhibit outstanding capacity in enhancing the magnetic resonance imaging (MRI) contrast between tumor tissues and normal tissues for generating bright images. However, the clinical application of representative gadolinium(III) chelate-based T1 CAs is limited due to their potential toxicity and low specificity for pathological tissues. To obtain MRI CAs with a combination of low toxicity and high tumor specificity, herein, we report a reactive oxygen species (ROS)-responsive T1 CA (GA-Fe(II)-PEG-FA), which was constructed by chelating Fe(II) with gallic acid (GA), and modified with tumor-targeted folic acid (FA). The resultant CA could accumulate in tumor tissues via the affinity between FA and their receptors on the tumor cell membrane. It realized the switch from Fe(II) to Fe(III), and further enhancing the longitudinal relaxation rate (r1) under the stimuli of ROS in the tumor microenvironment. The r1 of GA-Fe(II)-PEG-FA on a 0.5 T nuclear magnetic resonance analyzer increased to 2.20 mM-1 s-1 under ROS stimuli and was 5 times greater than the r1 (0.42 mM-1 s-1) before oxidation. The cell and in vivo experiments demonstrated that GA-Fe(II)-PEG-FA exhibited good biocompatibility and significant targeting specificity to tumor cells and tumor tissues. Furthermore, in vivo MRI studies demonstrated that the enhanced T1 contrast effect against tumors could be achieved after injecting the CA for 3 h, indicating that GA-Fe(II)-PEG-FA has the potential as an ideal tumor MRI CA to increase the contrast and improve the diagnostic precision.

Electrospun tannin-rich nanofibrous solid-state membrane for wastewater environmental monitoring and remediation.

Heavy metal, organic dyes, and bacterial contamination in water endanger human/animals' health, and therefore, the detection, adsorption, and capturing of contaminants are essential for environmental safety. Ligand-rich membranes are promising for sensors, adsorption, and bacterial decontamination. Herein, tannin (TA)-reinforced 3-aminopropyltriethoxysilane (APTES) crosslinked polycaprolactone (PCL) based nanofibrous membrane (PCL-TA-APTES) was fabricated via electrospinning. PCL-TA-APTES nanofibers possess superior thermal, mechanical, structural, chemical, and aqueous stability properties than the un-crosslinked membrane. It changed its color from yellowish to black in response to Fe2+/3+ ions due to supramolecular iron-tannin network (FeTA) interaction. Such selective sensing has been noticed after adsorption-desorption cycles. Fe3+ concentration, solution pH, contact time, and ligand concentration influence FeTA coordination. Under optimized conditions followed by image processing, the introduced membrane showed a colorimetric linear relationship against Fe3+ ions (16.58 µM-650 µM) with a limit of detection of 5.47 µM. The PCL-FeTA-APTES membrane could restrain phenolic group oxidation and result in a partial water-insoluble network. The adsorption filtration results showed that the PCL-FeTA-APTES membrane can be reused and had a higher methylene blue adsorption (32.04 mg/g) than the PCL-TA-APTES membrane (14.96 mg/g). The high capture efficiency of nanocomposite against Fe3+-based S. aureus suspension than Fe3+-free suspension demonstrated that Fe3+-bounded bacterium adhered to the nanocomposite through Fe3+/TA-dependent biointerface interactions. Overall, high surface area, rich phenolic ligand, porous microstructure, and super-wetting properties expedite FeTA coordination in the nanocomposite, crucial for Fe2+/3+ ions sensing, methylene blue adsorption-filtration, and capturing of Fe3+-bounded bacterium. These multifunctional properties could promise nanocomposite membrane practicability in wastewater and environmental protection.

Aptamer-Targeted Photodynamic Platforms for Tumor Therapy.

Achieving controlled and accurate delivery of photosensitizers (PSs) into tumor sites is a major challenge in conventional photodynamic therapy (PDT). Aptamer is a short oligonucleotide sequence (DNA or RNA) with a folded three-dimensional structure, which can selectively bind to specific small molecules, proteins, or the whole cells. Aptamers could act as ligands and be modified onto PSs or nanocarriers, enabling specific recognition and binding to tumor cells or their membrane proteins. The resultant aptamer-modified PSs or PSs-containing nanocarriers generate amounts of reactive oxygen species with light irradiation and obtain superior photodynamic therapeutic efficiency in tumors. Herein, we overview the recent progress in the designs and applications of aptamer-targeted photodynamic platforms for tumor therapy. First, we focus on the progress on the rational selection of aptamers and summarize the applications of aptamers which have been applied for targeted tumor diagnosis and therapy. Then, aptamer-targeted photodynamic therapies including various aptamer-PSs, aptamer-nanocarriers containing PSs, and aptamer-nano-photosensitizers are highlighted. The aptamer-targeted synergistically therapeutic platforms including PDT, photothermal therapy, and chemotherapy, as well as the imaging-guided theranostics, are also discussed. Finally, we offer an insight into the development trends and future perspectives of aptamer-targeted photodynamic platforms for tumor therapy.

Applications of nanomaterials for scavenging reactive oxygen species in the treatment of central nervous system diseases.

Reactive oxygen species (ROS) are the key signaling molecules in many physiological processes and play an important role in the development and function of the central nervous system (CNS). However, the process of CNS diseases is often accompanied by excessive production of ROS, which will induce oxidative stress, aggravate the pathological changes of the diseases, and cause neuroinflammation and loss of neurons. Therefore, it is beneficial for the treatment of CNS diseases and the recovery of the nerve function to eliminate the excessive ROS formed during the pathological changes of the CNS. Although several antioxidants have been proved to restore redox balance, their disappointing clinical performance has predicted less optimistic prospects in antioxidant therapy for ROS-associated CNS diseases. In recent years, nanomaterials with ROS-scavenging ability have been considered as promising substances to alleviate oxidative stress in CNS diseases because of their excellent ROS scavenging effect and biodistribution. This review article aims to elucidate the ROS scavenging mechanisms of various nanomaterials, introduce the reasons for ROS generation in CNS diseases, and review the applications of nanomaterials in scavenging ROS in CNS diseases reported in recent years.

Tumor Acid Microenvironment-Triggered Self-Assembly of ESIONPs for T1/T2 Switchable Magnetic Resonance Imaging.

Smart magnetic resonance imaging (MRI) contrast agents (CAs), whose MRI contrasting enhancement is variable in response to the specific stimulus from tumor tissues, possess great potential in precise tumor diagnosis. Herein, we design a type of extremely small iron oxide nanoparticle (ESIONP)-based pH-responsive system for activatable T2 MRI in the tumor acid microenvironment. The ESIONP system is composed of ESIONP-PEG-PGA and ESIONP-PEG-PDC, which were respectively constructed through the surface modification with poly (l-glutamic acid) (PGA) and poly(N-{N'-[N″-(2-carbox aminoethyl)]-2-aminoethyl}glutamide) (PDC) on the surface of ESIONP. The pH-responsive system exhibits the dispersed state under the neutral condition, and when it is exposed to the weakly acid environment, ESIONP-PEG-PDC switches from the neutral to positive charge, finally leading to the aggregation by the electrostatic interaction between the positively charged ESIONP-PEG-PDC and negatively charged ESIONP-PEG-PGA. On the basis of the aggregation, the T1 contrasting effect of the pH-responsive system switches to a T2 contrasting effect, which can be employed to realize the selective enhancement of imaging contrast at the tumor location owing to the weakly acid microenvironment. Moreover, on the basis of size increase originated from the aggregation effect, the residence time of extremely small iron oxide nanoparticles (ESIONPs) in the tumor site is effectively prolonged, which is beneficial for the MRI of tumors. Therefore, the pH-responsive system based on the ESIONPs is a potential smart MRI contrast agent for accurate tumor diagnosis.

Tumor Microenvironment-Responsive and Catalytic Cascade-Enhanced Nanocomposite for Tumor Thermal Ablation Synergizing with Chemodynamic and Chemotherapy.

Chemodynamic therapy (CDT) is considered as a promising nanocatalytic therapeutic strategy for cancer because of its specific response toward the tumor microenvironment (TME). Improving the efficiency of this kind of reactive oxygen species (ROS)-mediated therapy is still a formidable challenge. Herein, we integrate CDT with other therapeutic methods together to enhance anticancer effects via overcoming robust ROS defensive mechanisms and hypoxia in cancer cells. The biocompatible and biodegraded nanoplatform (HMnO2-DOX-GOD-HA) has been constructed on the basis of hollow MnO2 nanoparticles loaded with chemotherapeutics doxorubicin (DOX) and glucose oxide (GOD) and further decorated with hyaluronic acid (HA) for targeting tumor cells. We demonstrated that HMnO2-DOX-GOD-HA is not only able to deplete glutathione (GSH) to disturb the redox balance but also release Mn2+ to initiate the magnetic resonance imaging signal and induce Fenton reaction happening. Meanwhile, GOD-induced glucose oxidation and HMnO2-catalyzed O2 generation facilitate hypoxia relief and enhance toxic hydroxyl radical (•OH) production for CDT efficiency promotion. Upon 808 nm laser irradiation, cancer-killing efficiency can be notably increased by photothermally enhanced ion and drug release and thermal ablation. This work offers a paradigm to design a TME-responsive and imaging-guided synergistic strategy for hypoxia tumors based on GSH depletion and catalytic cascade-enhanced CDT, thermal ablation, and chemotherapy.

A magnetically recyclable superparamagnetic silica supported Pt nanocatalyst through a multi-carboxyl linker: synthesis, characterization, and applications in alkene hydrosilylation.

To simplify separation procedures, improve the reusability and decrease the loss of Pt, two Pt catalysts anchored on superparamagnetic silica (Fe3O4@SiO2-EDTA@Pt and Fe3O4@SiO2-DTPA@Pt) were prepared for the first time. The stable magnetic properties made them easily recyclable using a magnet rather than filtration, decantation or centrifugation. After 12 catalytic runs for both 30-50 nm Pt catalysts, the yield of 1-heptylmethyldichlorosilane was still up to 90%. The average loss of Pt in each reaction was only 0.87% for Fe3O4@SiO2-EDTA@Pt and 0.66% for Fe3O4@SiO2-DTPA@Pt owing to the strong interaction between Pt and carboxyl. The unprecedented activity and selectivity of the two Pt nanoparticle catalysts were observed in the hydrosilylation of alkenes. The turnover number in the reaction between 1-hexene and methyldichlorosilane using 5 × 10-8 mol of the Pt approached 662 733 for Fe3O4@SiO2-EDTA@Pt and 579 947 for Fe3O4@SiO2-DTPA@Pt over 12 h. The corresponding hydrosilylation products in excellent yields were obtained when we employed a broad range of alkenes as substrates, including 5 isomerous hexenes and 14 important industry raw materials. Fe3O4@SiO2-DTPA@Pt showed a better activity. They have potential for catalyzing more reactions and replacing the current homogeneous Pt catalysts in industry.