Target Biomolecules Research Articles

2-[(E)-(2-carboxybenzylidene) amino] ethan ammonium-like amino acid zwitterions: crystal structure, functional studies and its molecular dynamic simulation study with drug target receptors

The novel synthetic amino acid-like zwitterion containing imine bond ionic compound 2-[(E)-(2-carboxy benzylidene) amino] ethan ammonium salt, C10H12N2O2, was synthesized. Computational functional characterization is now being used to predict novel compounds. Here, we report on a titled combination that has been crystallizing in orthorhombic space group Pcc2 with Z = 4. The zwitterions form centrosymmetric dimers to polymeric supramolecular network via intermolecular N—H… O hydrogen bonds between the carboxylate groups and ammonium ion. The components are linked by ionic (N+–H–O−) and hydrogen bonds (N+–H–O), forming a complex three-dimensional supramolecular network. Further, molecular computational docking characterization study was performed with compound against multi-disease drug target biomolecule of anticancer target molecule of HDAC8 (PDB ID 1T69) receptor and antiviral molecular target protease (PDB ID 6LU7) to evaluate the interaction stability, conformational changes and to get insights into the natural dynamics on different timescales in solution. Highlights The novel zwitter ionic amino acid compound 2-[(E)-(2-carboxybenzylidene) amino] ethan ammonium salt, C10H12N2O2. The crystal structure determined for this compound illustrates the presence of intermolecular ionic N+–H–O− and N+–H–O hydrogen bonds between the carboxylate groups and ammonium ion, which influence the formation of a complex three-dimensional supramolecular polymeric network. Molecular docking studies helps to understand the conformational stability and interaction stability The novel molecule can be considered for anticancer treatment.

Amino-Termination of Silicon Carbide Nanoparticles.

Silicon carbide nanoparticles (SiC NPs) are promising inorganic molecular-sized fluorescent biomarkers. It is imperative to develop methods to functionalize SiC NPs for certain biological applications. One possible route is to form amino groups on the surface, which can be readily used to attach target biomolecules. Here, we report direct amino-termination of aqueous SiC NPs. We demonstrate the applicability of the amino-terminated SiC NPs by attaching bovine serum albumin as a model for functionalization. We monitor the optical properties of the SiC NPs in this process and find that the fluorescence intensity is very sensitive to surface termination. Our finding may have implications for a few nanometers sized SiC NPs containing paramagnetic color centers with optically read electron spins.

Controllable interfacial coupling of graphene in papermaking process for selective bio-detection with high sensitivity

Carbon paper-based electrochemical sensors offer the possibility of long-term in vivo monitoring of the biomarkers due to their chemical stability and porous structure. However, the serious self-staking and aggregation of the carbon materials seriously block the diffusion of target biomolecules and limit the sensitivity and selectivity of the device. Here we report a controllable interfacial coupling strategy in which a composite paper electrode made by electrostatic self-assembling reduced graphene oxide (rGO) on carbon fiber (CF) modified with cationic polyacrylamide to avoid the self-stacking in scalable wet papermaking and thus increased accessible electrochemically active surface area and accelerate the diffusion of biomarkers. The resulting composite paper shows improved stability, high selectivity, long-durability, and excellent sensitivity in the electrochemical detection of biomarkers such as ascorbic acid, dopamine, and uric acid. Our approach, which combines mature industrial paper technology with interface engineering and electrochemical reduction, offers a potential avenue for low-cost and scalable implantable electrodes for timely and long-term monitoring in the surgical and clinical applications.

Fabrication and nano-engineering of non-/noble metal-coupled plasmonic heterostructures for ultrasensitive photoelectrochemical immunoassays

To achieve reliable and ultrasensitive detection for disease markers in PEC bioanalysis, constructing and nano-engineering of ideal photoelectrodes and signal transduction strategies are of vital importance. Herein, a non-/noble metal coupled plasmonic nanostructure (TiO2/r-STO/Au) was tactically designed with high-efficient PEC performance. Evidenced by the DFT and FDTD calculations, the reduced SrTiO3 (r-STO) was found to support the localized surface plasmon resonance due to the sufficiently increased and delocalized local charge in r-STO. Under the synergistic coupling of plasmonic r-STO and AuNPs, the PEC performance of TiO2/r-STO/Au was found remarkably promoted with reduced onset potential. This merit supported TiO2/r-STO/Au as a self-powered immunoassay via a proposed oxygen-evolution-reaction mediated signal transduction strategy. With the increase of the target biomolecules (PSA), the catalytic active sites of TiO2/r-STO/Au would be blocked and result in the decrease of the oxygen evaluation reaction. Under optimal conditions, the immunoassays exhibited an excellent detection performance with a LOD as low as 1.1 fg/mL. This work proposed a new type of plasmonic nanomaterial for ultrasensitive PEC bioanalysis.

Naked-Eye Readout Distance Quantitative Lateral Flow Assay Based on the Permeability Changes of Enzyme-Catalyzed Hydrogelation.

Traditional lateral flow assay (LFA) is restricted to providing qualitative or semi-quantitative results and often requires special equipment for obtaining quantitative results. Herein, we proposed a naked-eye readout distance quantitative lateral flow assay based on the permeability changes in enzyme-catalyzed hydrogelation, which not only has the advantages of being simple, immediate, of high efficiency and low cost, and accurate in quantification but also avoids the use of special equipment. The developed LFA method includes three principal components of a nitrocellulose (NC) membrane containing a control line (C line) loading goat anti-rabbit (GAR) antibodies and a test line (T line) loading specific antibodies, alginate-tyramine conjugates forming a hydrogel in the presence of hydrogen peroxide (H2O2) and horseradish peroxidase (HRP), and the HRP-AuNPs-Ab probe only labeling targets captured on the T line. Hemoglobin A1c (HbA1c) was chosen as a representative example to demonstrate the feasibility of our method. Under the optimal conditions, the developed LFA method shows excellent performance in standard samples and real human blood samples where the results of real human blood samples show a high linear correlation with the clinical data obtained by ion exchange chromatography (R2 = 0.9929) and the margin of recovery is only 3.8%. All results demonstrated that our developed LFA method not only has enormous potential in the quantitative detection of HbA1c in clinical complex samples but also can serve as a versatile method for highly efficient detection of other target biomolecules due to the fungibility of antibodies.

Recent Advances in Biomolecular Detection Based on Aptamers and Nanoparticles.

The fast, accurate detection of biomolecules, ranging from nucleic acids and small molecules to proteins and cellular secretions, plays an essential role in various biomedical applications. These include disease diagnostics and prognostics, environmental monitoring, public health, and food safety. Aptamer recognition (DNA or RNA) has gained extensive attention for biomolecular detection due to its high selectivity, affinity, reproducibility, and robustness. Concurrently, biosensing with nanoparticles has been widely used for its high carrier capacity, stability and feasibility of incorporating optical and catalytic activity, and enhanced diffusivity. Biosensors based on aptamers and nanoparticles utilize the combination of their advantages and have become a promising technology for detecting of a wide variety of biomolecules with high sensitivity, reliability, specificity, and detection speed. Via various sensing mechanisms, target biomolecules have been quantified in terms of optical (e.g., colorimetric and fluorometric), magnetic, and electrical signals. In this review, we summarize the recent advances in and compare different aptamer-nanoparticle-based biosensors by nanoparticle types and detection mechanisms. We also share our views on the highlights and challenges of the different nanoparticle-aptamer-based biosensors.

A Highly Reliable Nanoscale Biodevice Benefitting from the Charge Plasma Concept – Si and InAs Source

A nanoscale biodevice based on the tunneling field effect transistor (TFET) has been reported for the detection of the target biomolecules. Two kinds of materials in the cases of silicon and InAs have been incorporated inside the source region for the sensitivity performance comparison. In order to prevent the diffusion of the impurities in the nanoscale biodevice during thermal proceeding, whole the structure has been doped at a N-type doped same level forming a junctionless device. The approach that we have benefited is the utilization of the charge plasma for converting the N-type source into the P-type source resulting in the creation of the TFET device, electrically. Indeed, the hole plasma will be appeared inside the source by the auxiliary plasma gate electrodes. The obtained results performed by the SILVACO simulator has shown the improvement of the sensitivity of the proposed biodevice while keeping the reliability high. Also, the fill-factor impact and trap-assisted-tunneling (TAT) issue as serious challenges on sensing performance are monitored for the biodevices under the study and the interesting results are presented.

Multimodal peptide ligand extracts parvovirus from interface in affinity aqueous two-phase system.

Aqueous two-phase systems (ATPS) have found various applications in bioseparations and microencapsulation. The primary goal of this technique is to partition target biomolecules in a preferred phase, rich in one of the phase-forming components. However, there is a lack of understanding of biomolecule behavior at the interface between the two phases. Biomolecule partitioning behavior is studied using tie-lines (TL), where each TL is a group of systems at thermodynamic equilibrium. Across a TL, a system can either have a bulk PEG-rich phase with citrate-rich droplets, or the opposite can occur. We found that porcine parvovirus (PPV) was recovered at a higher amount when PEG was the bulk phase and citrate was in droplets and that the salt and PEG concentrations are high. To improve the recovery, A PEG 10kDa-peptide conjugate was formed using the multimodal WRW ligand. When WRW was present, less PPV was caught at the interface of the two-phase system, and more was recovered in the PEG-rich phase. While WRW did not significantly increase the PPV recovery in the high TL system, which was found earlier to be optimal for PPV recovery, the peptide did greatly enhance recovery at a lower TL. This lower TL has a lower viscosity and overall system PEG and citrate concentration. The results provide both a method to increase virus recovery in a lower viscosity system, as well as provide interesting thoughts into the interfacial phenomenon and how to recover virus in a phase and not at the interface.

Robust Detection of Cancer Markers in Human Serums Using All-Dielectric Metasurface Biosensors

One of the most significant characteristics, which biosensors are supposed to satisfy, is robustness against abundant molecules coexisting with target biomolecules. In clinical diagnoses and biosensing, blood, plasma, and serum are used daily as samples. In this study, we conducted a series of experiments to examine the robustness of all-dielectric metasurface biosensors, which comprise pairs of a highly fluorescence-enhancing silicon nanopellet array and a transparent microfluidic chip. The metasurface biosensors were shown to have high performance in detecting various targets from nucleic acids to proteins, such as antigens and antibodies. The present results show almost four-order wide dynamic ranges from 0.16 ng/mL to 1 μg/mL for prostate-specific antigen (PSA) and from 2 pg/mL to 25 ng/mL for carcinoembryonic antigen (CEA). The ranges include clinical criteria for PSA, 4 ng/mL and CEA, 5 ng/mL. To date, a systematic demonstration of robustness has not been reported regarding the metasurface biosensors. In detecting cancer markers of PSA and CEA in human serums, we demonstrate that the metasurface biosensors are robust enough in a wide target concentrations, including the clinical diagnosis criteria.

Biomolecular Fishing: Design, Green Synthesis, and Performance of l-Leucine-Molecularly Imprinted Polymers.

Biopurification is a challenging and growing market. Despite great efforts in the past years, current purification strategies still lack specificity, efficiency, and cost-effectiveness. The development of more sustainable functional materials and processes needs to address pressing environmental goals, efficiency, scale-up, and cost. Herein, l-leucine (LEU)-molecularly imprinted polymers (MIPs), LEU-MIPs, are presented as novel biomolecular fishing polymers for affinity sustainable biopurification. Rational design was performed using quantum mechanics calculations and molecular modeling for selecting the most appropriate monomers. LEU-MIPs were synthesized for the first time by two different green approaches, supercritical carbon dioxide (scCO2) technology and mechanochemistry. A significant imprinting factor of 12 and a binding capacity of 27 mg LEU/g polymer were obtained for the LEU-MIP synthesized in scCO2 using 2-vinylpyridine as a functional monomer, while the LEU-MIP using acrylamide as a functional monomer synthesized by mechanochemistry showed an imprinting factor of 1.4 and a binding capacity of 18 mg LEU/g polymer, both systems operating at a low binding concentration (0.5 mg LEU/mL) under physiological conditions. As expected, at a higher concentration (1.5 mg LEU/mL), the binding capacity was considerably increased. Both green technologies show high potential in obtaining ready-to-use, stable, and low-cost polymers with a molecular recognition ability for target biomolecules, being promising materials for biopurification processes.

Magnetite-Based Biosensors and Molecular Logic Gates: From Magnetite Synthesis to Application

In the last few decades, point-of-care (POC) sensors have become increasingly important in the detection of various targets for the early diagnostics and treatment of diseases. Diverse nanomaterials are used as building blocks for the development of smart biosensors and magnetite nanoparticles (MNPs) are among them. The intrinsic properties of MNPs, such as their large surface area, chemical stability, ease of functionalization, high saturation magnetization, and more, mean they have great potential for use in biosensors. Moreover, the unique characteristics of MNPs, such as their response to external magnetic fields, allow them to be easily manipulated (concentrated and redispersed) in fluidic media. As they are functionalized with biomolecules, MNPs bear high sensitivity and selectivity towards the detection of target biomolecules, which means they are advantageous in biosensor development and lead to a more sensitive, rapid, and accurate identification and quantification of target analytes. Due to the abovementioned properties of functionalized MNPs and their unique magnetic characteristics, they could be employed in the creation of new POC devices, molecular logic gates, and new biomolecular-based biocomputing interfaces, which would build on new ideas and principles. The current review outlines the synthesis, surface coverage, and functionalization of MNPs, as well as recent advancements in magnetite-based biosensors for POC diagnostics and some perspectives in molecular logic, and it also contains some of our own results regarding the topic, which include synthetic MNPs, their application for sample preparation, and the design of fluorescent-based molecular logic gates.

Naphthalene and its Derivatives: Efficient Fluorescence Probes for Detecting and Imaging Purposes.

Naphthalene, white crystalline solid having polycyclic aromatic hydrocarbon with characteristic mothball order is naturally present in crucial oils of various plants. Naphthalene derivatives are extensive drug resources and are use as wetting agents, surfactants and as insecticides. These derivatives exhibit unique photo physical and chemical properties. These characteristics make them the most studied group of organic compounds. Naphthalene dyes have rigid plane and large π-electron conjugation. Therefor they have high quantum yield and excellent photostability. Naphthalene based fluorescence probes due to hydrophobic nature exhibit excellent sensing and selectivity properties towards anions and cations and also used as a part of target biomolecules. In conjugated probe system, introducing naphthalene moiety caused improvement in photo-stability. Therefore among various conjugated framework, naphthalene derivatives are considered excellent candidate for the construction of organic electronic appliances. These derivatives are useful for a variety of applications owing to their strong fluorescence, electroactivity and photostability. This article is based upon investigation of photophysical properties of naphthalene derivatives and fluorescence detecting probe of naphthalene. For photophysical properties the techniques under investigation are UV visible spectroscopy and fluorescence spectroscopy. Concentration dependent spectra and solvatochromic shifts on UV visible spectra are also part of discussion.

Biomolecule classification by multiscale one-dimensional convolutional neural network.

Raman spectroscopy has been used as a powerful tool to identify biomolecules in various fundamental and clinical studies. In recent years, machine learning has been used in the spectroscopy field to extract the spectrum feature for biomolecule classification and recognition. However, few methods have been developed for the classification of non-preprocessed spectra of biomolecules. The main challenge to deal with the spectra is the weak signals, strong backgrounds, and high bio-complexity. In this study, we developed a method to classify the membrane protein behavior in a nanometer-thin bilayer after an activator was applied. First, we used data augmentation to solve the problem of the sparsity of our spectrum data. Second, we constructed a multiscale 1D-CNN model for the spectrum classification. The ability to capture spectral features at different scales with the multiscale 1D-CNN model can deal with the difficulty to classify spectra of the complex cell membrane system. Last, score-CAM was used for model visualization to explain which spectrum features were used for the classification. The results show that our proposed multiscale 1D-CNN can improve the model performance metrics of other conventional machine algorithms by 4% to 13%. In addition, the obtained heatmaps from score-CAM also provided reasonable interpretations for the classification results in the amide I and amide III spectrum regions. These results show that the method we developed can give a persuasive classification for target biomolecules and has the potential to be applied in the study of disease treatment and biochemical reactions.

Relation in ligand dynamics and protein mutation using unsupervised machine learning.

Drug resistance mutation, which decreases ligand binding affinity to the target biomolecule, is a crucial issue all over the world. To overcome this issue, many approaches are proposed and tried. Free energy calculations are an effective and widely used method to estimate the ligand binding affinity. Relative free energy calculations can estimate the influence of the mutation on the ligand binding. However, the accuracy of the estimation should be limited partly because of insufficient sampling and relaxation of the mutants in the short molecular dynamics (MD) simulations. On the other hand, longer MD simulations make the calculation cost incredibly expensive. To improve the accuracy and computational cost, we have performed a machine-learning-assisted analysis of MD simulations [Yasuda, Commun. Biol. (2022)] of mutant protein-ligand systems. We used nilotinib-Abl-kinase systems, which were previously reported by other groups [Hauser, Commun. biol. (2018), Aldeghi, ACS Cent. Sci. (2019) ]. Our approach can compare the difference in the protein dynamics on ligand binding using unsupervised learning and extracts features of the dynamics of each mutant protein. We will show the relation of the feature to the ligand-binding affinity. Furthermore, interpretation of the feature enables us to understand the part of the ligand that shows different dynamics induced by the mutants. This would provide hints for the mechanics of the binding and improvements of the ligand.

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules.

The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, 99mTc, and the therapeutic radionuclide, 188Re, can potentially enable receptor-targeted "theranostic" treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type Ph2PCH2CH2P(CH2CH2-Glc)2 (L, where Glc = a glucose moiety) using the readily accessible Ph2PCH2CH2PH2 and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose-chelator conjugates can be radiolabeled with either 99mTc(V) or 188Re(V) in high radiochemical yields (>95%), to furnish separable mixtures of cis- and trans-[M(O)2L2]+ (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and ex vivo biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both cis-[99mTc(O)2L2]+ and trans-[99mTc(O)2L2]+ exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular 99mTc SPECT imaging and 188Re systemic radiotherapy.

A guide to small fluorescent probes for single-molecule biophysics

The explosive growth of single-molecule techniques is transforming our understanding of biology, helping to develop new physics inspired by emergent biological processes, and leading to emerging areas of nanotechnology. Key biological and chemical processes can now be probed with new levels of detail, one molecule at a time, from the nanoscopic dynamics of nature's molecular machines to an ever-expanding range of exciting applications across multiple length and time scales. Their common feature is an ability to render the underlying distribution of molecular properties that ensemble averaging masks and to reveal new insights into complex systems containing spatial and temporal heterogeneity. Small fluorescent probes are among the most adaptable and versatile for single-molecule sensing applications because they provide high signal-to-noise ratios combined with excellent specificity of labeling when chemically attached to target biomolecules or embedded within a host material. In this review, we examine recent advances in probe designs, their utility, and applications and provide a practical guide to their use, focusing on the single-molecule detection of nucleic acids, proteins, carbohydrates, and membrane dynamics. We also present key challenges that must be overcome to perform successful single-molecule experiments, including probe conjugation strategies, identify tradeoffs and limitations for each probe design, showcase emerging applications, and discuss exciting future directions for the community.

Structural tailoring of semiconducting tetrazine polymers based immobilizing matrix for superior electronic biosensing of carcinoembryonic antigen

AbstractImmobilizing matrix plays a crucial role in anchoring the receptors of target biomolecules and enhancing the sensing capability of biosensor. Howbeit, the immobilization platforms that induce stable molecular interactions with the receptors without the need for harsh reaction conditions (covalent bonding) are rare. Herein, we report the design, development and application of novel semiconducting one‐dimensional (1D) tetrazine polymers (TTz, PhTTz, PhAlkTz) as immobilizing matrices for electronic biosensing of carcinoembryonic antigen (CEA), a cancer biomarker. The polymers are fully loaded with electron‐deficient tetrazine units (nitrogen‐rich), which develop strong hydrogen bonding (H‐bonding) interactions and effectively immobilize the bioreceptor (anti‐CEA). The sensor comprises reduced graphene oxide (rGO) as the base conducting layer and tetrazine polymers as immobilizing matrices for the CEA antibodies. The rGO/TTz/anti‐CEA, rGO/PhTTz/anti‐CEA, rGO/PhAlkTz/anti‐CEA sensors exhibited 3.5 to 34.16 μA, 2.2 to 34.89 μA, 1.1 to 39.27 μA responses, respectively, for 1 pg/ml to 200 ng/ml of CEA. The sensors' (TTz, PhTTz, and PhAlkTz) sensitivities, selectivities and stabilities are found to be better than that of previously reported partially tetrazine loaded polymer (PhPTz). The study discloses the presence of H‐bonding in tetrazine units is highly critical for superior sensing. The concept of utilizing N‐rich tetrazine units in the immobilizing platforms can be generalized to several other hetero‐atom based systems and polymers. Thus, a wide variety of novel immobilizing substrates can be developed to realize superior sensing performance.

Natural oxidase-mimicking copper-organic frameworks for targeted identification of ascorbate in sensitive sweat sensing

Sweat sensors play a significant role in personalized healthcare by dynamically monitoring biochemical markers to detect individual physiological status. The specific response to the target biomolecules usually depends on natural oxidase, but it is susceptible to external interference. In this work, we report tryptophan- and histidine-treated copper metal-organic frameworks (Cu-MOFs). This amino-functionalized copper-organic framework shows highly selective activity for ascorbate oxidation and can serve as an efficient ascorbate oxidase-mimicking material in sensitive sweat sensors. Experiments and calculation results elucidate that the introduced tryptophan/histidine fundamentally regulates the adsorption behaviors of biomolecules, enabling ascorbate to be selectively captured from complex sweat and further efficiently electrooxidized. This work provides not only a paradigm for specifically sweat sensing but also a significant understanding of natural oxidase-inspired MOF nanoenzymes for sensing technologies and beyond.

A new application of papain: As a peroxidase-like catalyst for fluorometric detection of uric acid

Papain, as a classical cysteine protease, has been widely used in the food, pharmaceutical, chemical, and cosmetic fields. However, there are few information about the peroxidase-like activity of papain catalyzed substrate to produce fluorescence. In this study, we found that papain can catalyze H2O2 to convert o-phenylenediamine (OPD), and generate fluorescence emission at 550 nm under 430 nm excitation. Based on this foundation, we report a papain/OPD/H2O2 system for fluorescence detection of uric acid. The method exhibits a wide linear range of 10–1000 μM with a limit-of-detection of 4.6 μM, and has been successfully used to detect uric acid in human serum. This study paves the way for the application of papain as catalyst for fluorescence detection of different target biomolecules, such as cholesterol, glucose, lactate, for which H2O2 is a product of oxidoreductase enzymes.

Incorporation of Targeting Biomolecule Improves Interpolymer Complex-Superparamagnetic Iron Oxide Nanoparticles Attachment to and Activation of T2 MR Signals in M2 Macrophages.

Inflammatory diseases are the leading cause of death in the world, accounting for 3 out of 5 deaths. Despite the abundance of diagnostic tools for detection, most screening and diagnostic methods are indirect and insufficient as they are unable to reliably discriminate between high-risk or low-risk stages of inflammatory diseases. Previously, we showed that the selective activation of interpolymer complexed superparamagnetic iron oxide nanoparticles (IPC-SPIOs) under oxidative conditions can be detected by a change in T2 magnetic resonance (MR) contrast. In this work, IPC-SPIOs were further modified by incorporating mannose as a targeting biomolecule to enhance nanoparticle delivery to M2 macrophages at inflammatory sites. Uncoated SPIOs were synthesized via coprecipitation from a mixture of FeCl2 and FeCl3, PEGylated by adsorbing PEG 300 kDa (40 mg/mL in water) to SPIOs (3 mg/mL in water) over 24 hours, and complexed by mixing 0.25 mg/mL aqueous poly(gallol) with 2 mg/mL PEG-SPIOs and adding 1 M of phosphate buffer in a 9:9:2 ratio. Mannose-PEG attachment was accomplished conducting a second complexation of mannose-PEG to IPC-SPIOs. M2 macrophages were treated with 150, 100, and 75 µg/mL of IPC-SPIOs and mannose-IPC-SPIOs to investigate activation of T2 MRI signals. Surface modification resulted in a slight reduction in ROS scavenging capacity; however, nanoparticle uptake by M2 macrophages increased by over 50%. The higher uptake did not cause a reduction in cellular viability. In fact, mannose-IPC-SPIOs induced significant T2 MR contrast in M2 macrophages compared to IPC-SPIOs and nanoparticles exposed to M1 macrophages. M2 macrophages activated over 30% of mannose-IPC-SPIOs after 6 hours of exposure compared to M1 macrophages and untargeted M2 macrophages. These findings demonstrated that mannose-IPC-SPIOs specifically targeted M2 macrophages and scavenged cellular ROS to activate T2 MR signal, which can be used to detect inflammation.