A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy.

Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.

2D MOF Nanosensor-Integrated Digital Droplet Microfluidic Flow Cytometry for In Situ Detection of Multiple miRNAs in Single CTC Cells.

Current circulating tumor cells (CTCs) detection strategies based on surface epithelial markers suffer from low specificity in distinguishing between CTCs and epithelial cells in hematopoietic cell population. Tumor-associated miRNAs within CTCs are emerging as new biomarkers due to their high correlation with tumor development and progress. However, in-situ simultaneous analysis of multiple miRNAs in single CTC cell is still challenging. To overcome this limitation, a digital droplet microfluidic flow cytometry based on biofunctionalized 2D metal-organic framework nanosensor (Nano-DMFC) is developed for in situ detection of dual miRNAs simultaneously in single living breast cancer cells. Here, 2D MOF-based fluorescent resonance energy transfer (FRET) nanosensors are established by conjugating dual-color fluorescence dye-labeled DNA probes on MOF nanosheet surface. In the Nano-DMFC, 2D MOF-based nanoprobes are precisely microinjected into each single-cell encapsulated droplets to achieve dual miRNA characterization in single cancer cell. This Nano-DMFC platform successfully detects dual miRNAs at single-cell resolution in 10 mixed positive MCF-7 cells out of 10 000 negative epithelial cells in serum biomimic samples. Moreover, this Nano-DMFC platform shows good reproductivity in the recovery experiment of spiked blood samples, which demonstrate the high potential for CTC-based cancer early diagnosis and prognosis.

Saccharide-Functionalized Poly(Zn-salphen)-alt-(m- and p-phenyleneethynylene)s as Dynamic Helical Metallopolymers.

The study of metallopolymers with controllable helical sense remains in its infancy. We report arabinose-functionalized (Zn-salphen)-based conjugated polymers that display mirror-image circular dichroism spectra for L- and D-sugar sidechains respectively, signifying ordered (helical) coiling of the polymer backbone with opposite screw-sense preferences. The observation of different spectroscopic behavior and Cotton effects for a variety of solvents (in a reversible manner) and temperatures, ascribed to changes in the extent of intrachain (Zn⋅⋅⋅O(salphen) and π-stacking) interactions between Zn-salphen moieties, thus indicate the flexible, responsive and dynamic nature of the folded helical conformation in these systems. An application study signifying that activity can be governed by the structure and helical sense of the polymer is described.

Rapid and ultrasensitive detection of food contaminants using surface-enhanced Raman spectroscopy-based methods.

With the globalization of food and its complicated networking system, a wide range of food contaminants is introduced into the food system which may happen accidentally, intentionally, or naturally. This situation has made food safety a critical global concern nowadays and urged the need for effective technologies capable of dealing with the detection of food contaminants as efficiently as possible. Hence, Surface-enhanced Raman spectroscopy (SERS) has been taken as one of the primary choices for this case, due to its extremely high sensitivity, rapidity, and fingerprinting interpretation capabilities which account for its competency to detect a molecule up to a single level. Here in this paper, we present a comprehensive review of various SERS-based novel approaches applied for direct and indirect detection of single and multiple chemical and microbial contaminants in food, food products as well as water. The aim of this paper is to arouse the interest of researchers by addressing recent SERS-based, novel achievements and developments related to the investigation of hazardous chemical and microbial contaminants in edible foods and water. The target chemical and microbial contaminants are antibiotics, pesticides, food adulterants, Toxins, bacteria, and viruses. In this paper, different aspects of SERS-based reports have been addressed including synthesis and use of various forms of SERS nanostructures for the detection of a specific analyte, the coupling of SERS with other analytical tools such as chromatographic methods, combining analyte capture and recognition strategies such as molecularly imprinted polymers and aptasensor as well as using multivariate statistical analyses such as principal component analysis (PCA)to distinguish between results. In addition, we also report some strengths and limitations of SERS as well as future viewpoints concerning its application in food safety.

A sandwich-type surface-enhanced Raman scattering sensor using dual aptamers and gold nanoparticles for the detection of tumor extracellular vesicles.

A sandwich-type surface-enhanced Raman scattering (SERS) sensor using dual aptamers and gold-enhanced Raman signal probes has been successfully constructed for the detection of tumor-derived extracellular vesicles. The simple and sensitive sensor has the capability to detect tumor extracellular vesicles in 10-fold diluted human serum samples.

A fluorometric assay of thrombin using magnetic nanoparticles and enzyme-free hybridization chain reaction.

A fluorescence method based on functionalized magnetic nanoparticles (FMNPs) and hybridization chain reaction (HCR) is developed for the enzyme-free amplified determination of thrombin. In the proposed design, aptamer against thrombin was hybridized with the capture DNA-modified magnetic nanoparticles to yield the FMNPs. In the presence of thrombin, aptamers are released due to the specific and high-affinity binding between thrombin and its aptamer. The exposed capture DNA subsequently hybridized with the partial sequence of helper DNA, and the vacant sequence of helper DNA further hybridized with HCR products which is pre-formed by the alternate hybridization of single-stranded DNAs (H1 and H2). The immobilized HCR products were then labeled with YOYO-1 for fluorescence measurement. Fluorescence signal intensity of labeled YOYO-1 was measured at an emission wavelength of 519 nm (excitation under 488 nm) and used for calibration. By taking advantage of HCR amplification, this direct assay strategy showed a linear response in the 20- to 200-pM concentration range, and the limit of detection is 9.2 pM which is about 3-orders of magnitude lower than the serum thrombin concentration (10 nM) that triggers blood clotting. This developed method can efficiently differentiate the target protein from a protein matrix, and it is verified by determination of thrombin in spiked serum samples with recoveries in the range of 94.5-103.3%. Graphical abstract A fluorometry method for thrombin detection using magnetic nanoparticles and enzyme-free hybridization chain reaction.

Molecular-Recognition-Based DNA Nanodevices for Enhancing the Direct Visualization and Quantification of Single Vesicles of Tumor Exosomes in Plasma Microsamples.

Tumor exosomes (Exo) are presumed to expedite both the growth and metastasis of tumors by actively participating in nearly all aspects of cancer development. Tumor-derived Exos are thus proposed as a resource for diagnostic biomarkers in bodily fluids. However, most Exo assays require large samples and are time-consuming, complicated, and costly, and thus unsuited for practical applications. Herein, we show an ultrasensitive assay that can directly visualize and quantify tumor Exos in plasma microsamples (1 µL) at the single-vesicle level. The assay uses the specific binding of activatable aptamer probes (AAP) to target Exos captured by Exo-specific antibodies on the surface of a flow cell to produce activated fluorescence. Furthermore, the bound AAP triggers in situ assembly of a DNA nanodevice with enhanced fluorescence that improves the Exo-detection sensitivity. By identifying tyrosine-protein-kinase-like 7 (PTK7), a total-internal-reflection-fluorescence (TIRF) assay for PTK7-Exo distinguishes target tumors from control subjects. This assay is also informative in monitoring tumor progression and early responses to therapy. The developed assay can be readily adapted for diagnosis and monitoring of other disease-associated Exo biomarkers.

DNA-silver nanocluster probe for norovirus RNA detection based on changes in secondary structure of nucleic acids.

DNA-templated silver nanoclusters (DNA-AgNCs) is a kind of fluorescent nanoclusters in-situ synthesized on DNA, thereby giving the DNA probe an inherent function of label-free signal output. Herein, the DNA-AgNCs with a GCC-loop-structure which has a quantum field of 51.6% was firstly proposed. It was proved that the addition of the double-stranded structure on the GCC-loop drastically enhanced the fluorescence intensity of the AgNCs. Through the further studies of the relationship between DNA secondary structure and AgNCs, a kind of DNA-AgNCs-probe was designed based on the change of the secondary structure which was induced by the target strand. By this, the fluorescence signal of probe was in "turn on" mode. The probe system could be directly used for the detection of Norovirus RNA, which had a linearity of 20 nM to 1.8 µM with a detection limit of 18 nM. Moreover, this detection platform was also selective to differentiate mismatched RNA. It was expected to be a universal method for different RNA detection by changing the recognition sequence of the probe.

Homogeneous Immunosorbent Assay Based on Single-Particle Enumeration Using Upconversion Nanoparticles for the Sensitive Detection of Cancer Biomarkers.

Prostate-specific antigen (PSA) is an intercellular glycoprotein produced primarily by the prostate gland, which is commonly chosen as the initial target for the early diagnosis of prostate cancer. In this work, we demonstrate a simple yet sensitive sandwich-type single-particle enumeration (SPE) immunoassay for the quantitative detection of PSA in a flow chamber. The design is based on the luminescence resonance energy transfer (LRET) between upconversion nanoparticles (UCNPs) and gold nanoparticles (GNPs). The carboxyl group-functionalized UCNPs are conjugated with anti-PSA detection antibodies (Ab1) and serve as the luminescence energy donor, while GNPs are modified with anti-PSA capture antibodies (Ab2) and act as the energy acceptor. In the presence of target antigen (i.e., PSA), the specific immnuoreaction brings the donor and acceptor into close proximity, resulting in quenched luminescence. Through statistical counting of the target-dependent fluorescent particles on the glass slide surface, the quantity of antigens in the solution is accurately determined. The dynamic range for PSA detection in Tris-buffered saline (TBS) is 0-500 pM and the limit-of-detection (LOD) is 1.0 pM, which is much lower than the cutoff level in patients' serum samples. In the serum sample assay, comparable LOD was also achieved (i.e., 2.3 pM). As a consequence, this method will find promising applications for the selective detection of cancer biomarkers in clinical diagnosis.

A Zero Cross-Talk Ratiometric Two-Photon Probe for Imaging of Acid pH in Living Cells and Tissues and Early Detection of Tumor in Mouse Model.

Acid-base disorders disrupt proper cellular functions, which are associated with diverse diseases. Development of highly sensitive pH probes being capable of detecting and monitoring the minor changes of pH environment in living systems is of considerable interest to diagnose disease as well as investigate biochemical processes in vivo. We report herein two novel high-resolution ratiometric two-photon (TP) fluorescent probes, namely, PSIOH and PSIBOH derived from carbazole-oxazolidine π-conjugated system for effective sensing and monitoring acid pH in a biological system. Remarkably, PSIOH exhibited the largest emission shift of ∼169 nm from 435 to 604 nm upon pH changing from basic to acidic with an ideal p Ka value of 6.6 within a linear pH variation range of 6.2-7.0, which is highly desirable for high-resolution tracking and imaging the minor fluctuation of pH in live cells and tissues. PSIOH also exhibits high pH sensitivity, excellent photostability, and reversibility as well as low cytotoxicity. More importantly, this probe was successfully applied to (i) sense and visualize the pH alteration in HeLa cells caused by various types of exogenous stimulation and (ii) detect and differentiate cancer and tumors in liver tissues and a mouse model, realizing its practical in vitro and in vivo applications.

Dual-Modal NIR-Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid-ß Species In Vivo.

Senile plaques, the extracellular deposit of amyloid-ß (Aß) peptides, are one of the neuropathological hallmarks found in Alzheimer's disease (AD) brain. The current method of brain imaging of amyloid plaques based on positron emission tomography (PET) is expensive and invasive with low spatial resolution. Thus, the development of sensitive and nonradiative amyloid-ß (Aß)-specific contrast agents is highly important and beneficial to achieve early AD detection, monitor the disease progression, and evaluate the effectiveness of potential AD drugs. Here a neuroprotective dual-modal nanoprobe developed by integrating highly Aß-specific and turn-on fluorescence cyanine sensors with superparamagnetic iron oxide nanoparticles as an effective near-infrared imaging (NIRI)/magnetic resonance imaging (MRI) contrast agent for imaging of Aß species in vivo is reported. This Aß-specific probe is found not only nontoxic and noninvasive, but also highly blood brain barrier permeable. It also shows a potent neuroprotective effect against Aß-induced toxicities. This nanoprobe is successfully applied for in vivo fluorescence imaging with high sensitivity and selectivity to Aß species, and MRI with high spatial resolution in an APP/PS1 transgenic mice model. Its potential as a powerful in vivo dual-modal imaging tool for early detection and diagnosis of AD in humans is affirmed.

Enzyme-free quantification of exosomal microRNA by the target-triggered assembly of the polymer DNAzyme nanostructure.

We herein report an efficient hybridization chain reaction (HCR)- and DNAzyme-based enzyme-free signal amplification for the detection of specific exosomal miRNAs in the culture medium of cancer cells and serum samples from cancer patients via the target-triggered self-assembly of the polymer DNAzyme nanostructure.

Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation.

BACKGROUND: Silica nanoparticles (SiO2-NPs) are naturally enriched and broadly utilized in the manufacturing industry. While previous studies have demonstrated toxicity in neuronal cell lines after SiO2-NPs exposure, the role of SiO2-NPs in neurodegeneration is largely unknown. Here, we evaluated the effects of SiO2-NPs-exposure on behavior, neuropathology, and synapse in young adult mice and primary cortical neuron cultures. RESULTS: Male C57BL/6 N mice (3 months old) were exposed to either vehicle (sterile PBS) or fluorescein isothiocyanate (FITC)-tagged SiO2-NPs (NP) using intranasal instillation. Behavioral tests were performed after 1 and 2 months of exposure. We observed decreased social activity at both time points as well as anxiety and cognitive impairment after 2 months in the NP-exposed mice. NP deposition was primarily detected in the medial prefrontal cortex and the hippocampus. Neurodegeneration-like pathological changes, including reduced Nissl staining, increased tau phosphorylation, and neuroinflammation, were also present in the brains of NP-exposed mice. Furthermore, we observed NP-induced impairment in exocytosis along with decreased synapsin I and increased synaptophysin expression in the synaptosome fractions isolated from the frontal cortex as well as primary neuronal cultures. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were also activated in the frontal cortex of NP-exposed mice. Moreover, inhibition of ERK activation prevented NP-mediated changes in exocytosis in cultured neurons, highlighting a key role in the changes induced by NP exposure. CONCLUSIONS: Intranasal instillation of SiO2-NPs results in mood dysfunction and cognitive impairment in young adult mice and causes neurodegeneration-like pathology and synaptic changes via ERK activation.

Quantification of Cancer Biomarkers in Serum Using Scattering-Based Quantitative Single Particle Intensity Measurement with a Dark-Field Microscope.

In this work, we developed a simple yet robust single particle scattering intensity measurement method for the quantification of cancer-related biomarkers. The design is based on the plasmonic coupling effect between noble metal nanoparticles. First, the primary and secondary antibodies were conjugated onto the surface of 60 nm gold nanoparticles (AuNPs, act as capture probes) and 50 nm silver nanoparticles (AgNPs, act as signal amplification probes) respectively. In the presence of corresponding antigen, a sandwiched immunocomplex was formed, resulting a significantly enhanced scattering intensity in contrast to that of individual probes. By measuring the intensity change of the particles with a dark-field microscope (DFM), the amount of target protein could be accurately quantified. As a proof of concept experiment, quantification of three types of antigens, including carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and alpha fetoprotein (AFP) by this platform was demonstrated with limit of detection (LOD) of 1.7, 3.3, and 5.9 pM, respectively, with a linear dynamic range of 0 to 300 pM. Furthermore, to elucidate the potential in clinical application, the content of antigens in a serum sample was also quantified directly without additional sample pretreatment. In order to validate the reliability of this method, the measured result was also compared with that obtained by regular enzyme-linked immunosorbent assay (ELISA) kit, showing good consistency between these two data sets. Therefore, owing to the simplicity and accuracy of this method, it could be potentially applied for massive disease screening in clinical assay in the future.

Direct quantification of circulating miRNAs in different stages of nasopharyngeal cancerous serum samples in single molecule level with total internal reflection fluorescence microscopy.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate human gene expression at the post-transcriptional level. Growing evidence indicates that the expression profile of miRNAs is highly correlated with the occurrence of human diseases including cancers. Playing important roles in complex gene regulation processes, the aberrant expression pattern of various miRNAs is implicated in different types and even stages of cancer. Besides localizing in cells, many of these miRNAs are found circulating around the body in a wide variety of fluids such as urine, serum and saliva. Surprisingly, these extracellular circulating miRNAs are highly stable and resistant to degradation, and therefore, are considered as promising biomarkers for early cancer diagnostic via noninvasive extraction from body fluids. Unfortunately, the abundance of these small RNAs is ultralow in the body fluids, making it challenging to quantify them in complex sample matrixes. Establishing a sensitive, specific yet simple assay for an accurate quantification of circulating miRNAs is therefore desirable. Our group previously reported a sensitive and specific detection assay of miRNAs in single molecule level with the aid of total internal reflection fluorescence microscopy. In this work, we advanced the assay to differentiate the expression of a nasopharyngeal carcinoma (NPC) up-regulator hsa-mir-205 (mir-205) in serum collected from patients of different stages of NPC. To overcome the background matrix interference in serum, a locked nucleic acid-modified molecular beacon (LNA/MB) was applied as the detection probe to hybridize, capture and detect target mir-205 in serum matrix with enhanced sensitivity and specificity. A detection limit of 500 fM was achieved. The as-developed method was capable of differentiating NPC stages by the level of mir-205 quantified in serum with only 10 µL of serum and the whole assay can be completed in 1 h. The experimental results agreed well with those previously reported whereas the quantity of miR-205 determined by our assay was found comparable to that of quantitative reverse transcription polymerase chain reaction (qRT-PCR), supporting that this assay can be served as a promising noninvasive detection tool for early NPC diagnosis, monitoring and staging.

Monitoring of DNA-protein interaction with single gold nanoparticles by localized scattering plasmon resonance spectroscopy.

We reported a sensitive detection system for measuring DNA-protein interaction at single plasmonic metal nanoparticles level by Localized Scattering Plasmon Resonance (LSPR) spectroscopy. As a proof of concept, DNA molecules were conjugated to gold nanoparticles (AuNPs) through gold-thiol chemistry and the resulted complex was served as single-particle probes of human topoisomerase I (TOPO). By recording the changes in Rayleigh light scattering signal of the individual nanoparticles upon protein binding, DNA-protein interaction was monitored and measured. The λmax shifts in LSPR spectrum of individual AuNP was found to be highly correlated with the amount of TOPO that bound onto. This technique provides a sensitive and high-throughput platform to screen and monitor accurately the specific biomolecular interactions. It is capable of revealing information such as particle-particle variations that might be buried in conventional bulk measurement.

Nanomaterials that Aid in the Diagnosis and Treatment of Alzheimer's Disease, Resolving Blood-Brain Barrier Crossing Ability.

As a form of dementia, Alzheimer's disease (AD) suffers from no efficacious cure, yet AD treatment is still imperative, as it ameliorates the symptoms or prevents it from deteriorating or maintains the current status to the longest extent. The human brain is the most sensitive and complex organ in the body, which is protected by the blood-brain barrier (BBB). This yet induces the difficulty in curing AD as the drugs or nanomaterials that are much inhibited from reaching the lesion site. Thus, BBB crossing capability of drug delivery system remains a significant challenge in the development of neurological therapeutics. Fortunately, nano-enabled delivery systems possess promising potential to achieve multifunctional diagnostics/therapeutics against various targets of AD owing to their intriguing advantages of nanocarriers, including easy multifunctionalization on surfaces, high surface-to-volume ratio with large payloads, and potential ability to cross the BBB, making them capable of conquering the limitations of conventional drug candidates. This review, which focuses on the BBB crossing ability of the multifunctional nanomaterials in AD diagnosis and treatment, will provide an insightful vision that is conducive to the development of AD-related nanomaterials.

Molecular engineering of a theranostic molecule that detects Aß plaques, inhibits Iowa and Dutch mutation Aß self-aggregation and promotes lysosomal biogenesis for Alzheimer's disease.

Extracellular clustering of amyloid-ß (Aß) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aß1-42, Iowa mutation Aß, Dutch mutation Aß fibrils and oligomers exhibiting enhanced emission with high affinity. Importantly, F-SLCOOH can readily pass through the blood-brain barrier and shows highly selective binding toward the extracellular Aß aggregates in real-time in live animal imaging of a 5XFAD mice model. In addition, a high concentration of F-SLCOOH in both brain and plasma of wildtype mice after intraperitoneal administration was found. The ex vivo confocal imaging of hippocampal brain slices indicated excellent colocalization of F-SLCOOH with Aß positive NU1, 4G8, 6E10 A11 antibodies and THS staining dye, affirming its excellent Aß specificity and targetability. The molecular docking studies have provided insight into the unique and specific binding of F-SLCOOH with various Aß species. Importantly, F-SLCOOH exhibits remarkable anti-fibrillation properties against toxic Aß aggregate formation of Aß1-42, Iowa mutation Aß, and Dutch mutation Aß. F-SLCOOH treatment also exerts high neuroprotective functions and promotes autophagy lysosomal biogenesis in neuronal AD cell models. In summary, the present results suggest that F-SLCOOH is a highly promising theranostic agent for diagnosis and therapeutics of AD.

Ultrasensitive miRNA Detection by AuNP-based 3D DNA Walker and Catalytic Hairpin Assembly (CHA) Cascade Amplification for Early Cancer Diagnosis.

By combining exquisitely designed hairpins with the catalytic hairpin assembly (CHA) to form tripedal DNA walkers driven by enzyme, we constructed a 3D DNA walker with accordingly complementary hairpins attached on gold nanoparticles (AuNPs) and sensitive fluorescence sensing system for the sensitive detection of target miRNA-21 (miR-21). The presence of miR-21 triggers the CHA among three hairpins (HP1, HP2, and HP3), which lead to the formation of the tripedal DNA walkers. For the walking trajectories, FAM-labeled hairpins (HP4) were attached to the surface of AuNPs, the fluorescence of which was initially quenched due to its close proximity to AuNPs. After the binding/cleaving/moving process of tripedal DNA walkers with HP4 driven by Exonuclease III (Exo III), a number of single-stranded DNAs (ssDNAs) will be released with FAM fluorescence recovered. Benefiting from the DNA walker and CHA cascade amplification, the proposed sensing strategy showed remarkable improvement in sensitivity with the LOD of 42 aM. Owing to the precise design of the system, this method exhibited excellent specificity to distinguish miR-21 from its single-, double-mismatched sequences and non-complementary sequences, showing great versatility and potential for the biological analysis and early disease diagnosis.

Multifunctional theranostic carbazole-based cyanine for real-time imaging of amyloid-ß and therapeutic treatment of multiple pathologies in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by the synaptic and neuronal loss, which results in cognitive impairment in particular learning and memory. Currently, AD is incurable and no single confirmative test can clinically be used to diagnose AD. In light of the complex and multifactorial nature of AD etiology, the development of multifunctional/multi-target drugs that act on multiple pathological pathways and mechanisms shows great therapeutic potential for intervention of this devastating disease. We report herein a multifunctional theranostic cyanine, SLCOOH, which serves not only as a highly sensitive fluorescent probe for real-time imaging of amyloid-ß (Aß) contents in different age groups of transgenic (Tg) AD mice but also as an effective therapeutic agent for early AD intervention via multiple pathological targets in the AD mouse model. Remarkably, treatment with SLCOOH gives rise to multiple therapeutic benefits, including the amelioration of cognitive decline, a reduction in Aß levels, a decrease in hyperphosphorylated tau proteins and tau depositions, and the alleviation of synaptic loss and dysfunctions in young triple Tg AD mice. Our results have demonstrated that in addition to superior Aß imaging capability, SLCOOH exhibits versatile and effective multiple modes of drug action, signifying outstanding therapeutic potential to treat early onset AD. Our work also paves the way for the development of effective Aß-targeted theranostic agents for AD.