Dual-modality Imaging Research Articles

Aggregation-Mediated Photoacoustic/NIR-II and Photodynamic Properties of pH-Reversible Thiopyrylium Agents: A Computational and Experimental Approach.

Aggregation profoundly influences the photophysical properties of molecules. Here, a new series of thiopyrylium-based hemicyanine near-infrared II (NIR-II) fluorophores is developed by meticulously adjusting their aggregation states. Notably, the star molecule HTPA exhibits a remarkable pH-responsive behavior and a significant increase in photoacoustic (PA) intensity when aggregated. Additionally, their behavior and pH reversibility during aggregation formation are systematically investigated, including computational optimization, femtosecond transient absorption spectroscopy, NMR analysis, and single crystal analysis. Finally, an innovative "off " nanoparticle specifically is designed for effective tumor-targeted PA/NIR-II dual-modal imaging and photodynamic therapy by utilizing a pH-responsive polymer. The signal-to-background ratio (SBR) of PA signals significantly increased to 169 in the region of interest (ROI) in the mouse model when irradiated at 1064nm. These findings not only provide a promising avenue for future studies of NIR-II small molecules but also pave the way for significant advances in the field of integrated cancer diagnosis and therapy.

Application of therapeutical nanoparticles with neutrophil membrane camouflaging for inflammatory plaques targeting against atherosclerosis.

Atherosclerosis is the leading cause of cardiovascular disease and myocardial infarction. Precise and effective plaque targeting is a major objective for therapeutic outcomes throughout various stages of atherosclerosis. Inspired by the natural recruitment of neutrophils in atherosclerotic plaques, we fabricated a simvastatin (ST)-loaded and neutrophil membrane-cloaked nanoplatform (NNPST) for enhancing localized payload delivery and atherosclerosis management. The resulting NNPST mimicked neutrophil function and significantly decreased macrophage-mediated phagocytosis to prolong its own circulation time in the blood. Compared to pristine nanoparticles (NPST) without a membrane coating, NNPST achieved better plaque targeting in ApoE-/- mice, as indicated by neutrophils actively recruited in atherosclerotic lesions. The higher plaque homing with NNPST was monitored by dynamic fluorescence/magnetic resonance (MR) dual-modality imaging. The results further showed that NNPST efficiently prevented atherosclerosis development mainly by suppressing local inflammatory macrophages, and the percentage of plaques in the entire aortic area was reduced to 4.75±1.48% following NNPST treatment. A biosafety assessment indicated that the biomimetic NNPST induced no noticeable toxicity in the body. This approach of neutrophil membrane-camouflaged nanoparticles offers new opportunities to various therapeutic agents for on-demand delivery in neutrophil-involved inflammatory diseases.

Conversion therapy strategy: A novel GPC3-targeted multimodal organic phototheranostics platform for mid-late-stage hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is typically diagnosed at intermediate to advanced stage, making surgical treatment unfeasible. Conversion therapy aims to reduce tumor stage, improve hepatic resection feasibility, and lower recurrence rates. Since traditional therapies are often accompanied by uncertainty of efficacy, there is an urgent need to explore new treatment strategies. Near-infrared phototheranostics technology provides a new way for HCC diagnosis and treatment by its excellent optical properties. However, complex preparation and poor biocompatibility of phototheranostics probes limit clinical application. In this study, we developed a fluorescence/magnetic resonance dual-modality imaging (FLI/MRI) as well as photothermal/photodynamic therapy (PTT/PDT) GPC3-targeted multifunctional phototheranostics probe, IR820-GPC3-Gd NPs (IGD NPs), to improve the efficiency of conversion therapy for HCC. The IGD NPs were simply prepared with the IR820 as the core. Conjugating the HCC-specific targeting molecule GPC3 peptide and the MRI agent DOTA-Gd through click chemistry. IGD NPs target HCC cells through GPC3, releasing heat and reactive oxygen species (ROS) under noninvasive 808nm laser irradiation to reduce tumor size and achieve downstaging. High-sensitivity FLI/MRI precisely delineates tumor boundaries, providing real-time surgical navigation and prognosis assessment. This novel probe offers a feasible and effective treatment option for advanced HCC.

Triazination/IEDDA Cascade Modular Strategy Installing Pyridines/Pyrimidines onto Tyrosine Enables Peptide Screening and Optimization.

Modular chemical postmodification of peptides is a promising strategy that supports the optimization and innovation of hit peptide therapeutics by enabling rapid derivatization. However, current methods are primarily limited to traditional bio-orthogonal strategies and chemical ligation techniques, which require the preintroduction of non-natural amino acids and impose fixed methods that limit peptide diversity. Here, we developed the Tyrosine-1,2,3-Triazine Ligation (YTL) strategy, which constructs novel linkages (pyridine and pyrimidine) through a "one-pot, two-step" process combining SNAr and IEDDA reactions, promoting modular post modification of Tyr-containing peptides. After optimizing the YTL strategy and establishing standard procedures, we successfully applied it to the solid-phase postmodification of various biorelated peptides, such as the synthesis of dual-mode imaging probes and long-acting GLP-1 analogs. As a proof of concept, a library of 384 amphipathic peptides was constructed using YTL based on 96-well microfiltration plates. Modular modifications were then performed on the screened template tripeptide RYR, leading to the generation of 20 derivatives. The antibacterial activity of these derivatives was systematically characterized, identifying Z8 as a potential antibacterial candidate.

Application of a CYP1B1-Targeted NIR Probe for Breast Cancer Diagnosis, Surgical Navigation, and CYP1B1-Associated Chemotherapy Resistance Monitoring.

Early detection and precise treatment for breast cancer are crucial, given its high global incidence rate. Hence, the development of novel imaging targets is essential for diagnosing and monitoring resistance to chemotherapy, which is pivotal for achieving precise and personalized treatment for breast cancer patients. In our previous work, we successfully developed a near-infrared (NIR) probe 1 for CYP1B1-targeted imaging. In this study, we aimed to investigate the utility of the probe as a NIR fluorescence and photoacoustic dual-mode imaging probe for the detection and surveillance of breast cancer. Western blotting of cancer cell lines has confirmed that CYP1B1 is widely expressed in breast cancer and gynecological cancer. In vitro NIR fluorescence imaging capability of the probe for tracking CYP1B1-positive tumor cells was validated by using confocal microscopy. Further studies, including in vivo fluorescence and photoacoustic dual-model imaging and ex vivo biological distribution analysis on a triple-negative breast cancer xenograft mouse model, demonstrated that the probe selectively accumulated in tumor tissue within as early as 0.5 h postinjection. The results of the surgical resection experiment revealed that the tumor could be entirely removed under the guidance of NIR imaging, thereby indicating the probe's efficacy in surgical navigation. CYP1B1 expression was found to be upregulated in adriamycin (ADR)-resistant breast cancer cells, MCF-7/ADR. Consequently, the sensitivity of CYP1B1 overexpressed cells, MCF-7/1B1, to ADR was significantly reduced, with an IC50 value of 0.586 ± 0.0934 μM, compared to the parental MCF-7 cells with an IC50 value of 0.183 ± 0.0444 μM. In vivo and ex vivo imaging assays conducted on MCF-7/ADR tumor-bearing mice demonstrated that the probe was specifically enriched in tumor sites, suggesting its potential for monitoring chemotherapy resistance in breast cancer. This study expands the scope of application for NIR probe 1, establishing its utility in breast cancer diagnosis through fluorescence-photoacoustic dual-model imaging, monitoring of chemotherapy resistance, and guidance for surgical resection. This strategy paves the way for novel approaches to precise and personalized treatment for breast cancer patients.

PET-Based Dual-Modal Probes for In Vivo Imaging.

Molecular imaging has significantly advanced the detection and analysis of in vivo metabolic processes, while single-modal techniques remain limited. Dual-modal imaging, particularly positron emission tomography (PET)-based combinations has emerged as a powerful solution, offering enhanced capabilities through integration with magnetic resonance imaging (MRI) or near-infrared fluorescence (NIRF) imaging. This review highlights recent progress in PET-based dual-modal imaging, focusing on the development of various bimodal probes derived from antibodies, nanoparticles, and peptides, and key applications including image-guided surgery and disease assessment. PET-based dual-modal imaging holds substantial potential for advancing research and diagnostics by improving resolution and providing functional insights. By combining complementary modalities, these systems deliver a more comprehensive view of disease processes, leading to more accurate diagnoses and targeted treatments. Future research prioritizes optimizing probe design for enhanced biocompatibility and safety, facilitating clinical translation, and broadens applications beyond cancer. Through interdisciplinary collaboration, PET-based dual-modal probes are poised to play a pivotal role in improving patient outcomes, particularly in diagnosing and managing complex diseases.

Endogenous Protein-Modified Gold Nanorods as Immune-Inert Biomodulators for Tumor-Specific Imaging and Therapy.

Engineered modifications of nanomaterials inspired by nature hold great promise for disease-specific imaging and therapies. However, conventional polyethylene glycol modification is limited by immune system rejection. The manipulation of gold nanorods (Au NRs) modified by endogenous proteins (eP@Au) is reported as an engineered biomodulator for enhanced breast tumor therapy. The results show that eP@Au NRs neither activate inflammatory factors in vitro nor elicit rejection of immune responses in vivo. Tumor-specific eP@Au NRs exhibit a dual-modal imaging capability and trigger a mild photothermal effect under near-infrared light irradiation, enabling highly efficient imaging and therapy of tumors. Transcriptome sequencing and confirmatory experiments reveal that the antitumor effect is mainly attributed to the repression of PI3K-Akt/MAPK signaling pathways at the molecular level. This powerful and surprising in situ eP-regulated biomodulation demonstrates the advantages of convenient fabrication, inert immunogenicity, and biocompatibility, providing an alternative strategy for biomedical imaging and therapy.

Dual-Labeled Small Peptides in Cancer Imaging and Fluorescence-Guided Surgery: Progress and Future Perspectives

Dual-labeled compounds that combine radiolabeling and fluorescence labeling represent a significant advancement in precision oncology. Their clinical implementation enhances patient care and outcomes by leveraging the high sensitivity of radioimaging for tumor detection and taking advantage of fluorescence-based optical visualization for surgical guidance. Non-invasive radioimaging facilitates immediate identification of both primary tumors and metastases, while fluorescence imaging assists in decision-making during surgery by offering a spatial distinction between malignant and non-malignant tissue. These advancements hold promise for enhancing patient outcomes and personalization of cancer treatment. The development of dual-labeled molecular probes targeting various cancer biomarkers is crucial in addressing the heterogeneity inherent in cancer pathology and recent studies had already demonstrated the impact of dual-labeled compounds in surgical decision-making (NCT03699332, NCT03407781). This review focuses on the development and application of small dual-labeled peptides in the imaging and treatment of various cancer types. It summarizes the biomarkers targeted to date, tracing their development from initial discovery to the latest advancements in peptidomimetics. Through comprehensive analysis of recent preclinical and clinical studies, the review demonstrates the potential of these dual-labeled peptides to improve tumor detection, localization, and resection. Additionally, it highlights the evolving landscape of dual-modality imaging, emphasizing its critical role in advancing personalized and effective cancer therapy. This synthesis of current research underscores the promise of dual-labeled peptides in enhancing diagnostic accuracy and therapeutic outcomes in oncology.

Targeted Modulation of the Meningeal Lymphatic Reverse Pathway for Immunotherapy of Breast Cancer Brain Metastases.

Treatment of tumor brain metastases remains challenging due to the ineffectiveness of drugs in crossing the blood-brain barrier (BBB). Here, we proposed a potential strategy to target and modulate the meningeal lymphatic system for immunotherapy of breast cancer brain metastases (BCBM) through peripheral administration. CT/fluorescence dual-modality imaging demonstrated that the phospholipid nanoprobe (α-PLNPs) through intracisternal magna injection effectively labeled and long-range tracked the meningeal lymphatic pathway from meningeal lymphatic vessels (MLVs) to periphery drainage cervical lymph nodes (CLNs). Interestingly, the reverse pathway from CLNs to MLVs was also successfully labeled with α-PLNPs through cervical subcutaneous injection, facilitating the noninvasive delivery of immunomodulators to the meningeal lymphatics. Given this, we used melittin-carrying α-M-PLNPs to trigger the modulation of the meningeal lymphatic reverse pathway, which effectively prevents BCBM and prolongs the survival of mice through activating the antigen-presenting cells in the CLNs and promoting the migration of CD8+ T cells into the metastatic brain tumors. This study highlights the potential of the meningeal lymphatic reverse pathway for the immunotherapy of BCBM, which holds great promise for central nervous system disease therapy without the need for drug delivery via BBB.

Information merging and reconstruction of single-shot dual-mode wide-field imaging with high spatial resolution

In many scenarios, it is really desirable but challenging for wide-field imaging to gather both the clear morphologies and fine details of the target. This paper realizes this imaging by a dual-mode imaging on optical parametric amplification (OPA) with a vortex laser pump. This design includes signal imaging and idler imaging, which have complementary point spread functions with each other. The signal acts as bright-field imaging to record morphologic information, whereas the idler does so for spiral phase contrast imaging to capture the featured details with high brightness and contrast, which has been experimentally confirmed with a target of herb tissue. By utilizing the coupling relation among the pump, signal, and idler, the information from the recorded signal and idler images can be merged, which allows us to reconstruct the target picture owning both high-contrast morphologies and high-brightness fine details. Due to high OPA gain, our imaging can work with weak illumination. Its field-of-view covers an area of 0.33 × 0.33 mm2 with a spatial resolution up to 228 lp/mm. This OPA imaging also provides an effective way for the imaging required nonlinear frequency conversion.

All-In-One Entropy-Driven DNA Nanomachine for Tumor Cell-Selective Fluorescence/SERS Dual-Mode Imaging of MicroRNA.

An entropy-driven catalysis (EDC) strategy is appealing for amplified bioimaging of microRNAs in living cells; yet, complex operation procedures, lacking of cell selectivity, and insufficient accuracy hamper its further applications. Here, we introduce an ingenious all-in-one entropy-driven DNA nanomachine (termed as AIO-EDN), which can be triggered by endogenous apurinic/apyrimidinic endonuclease 1 (APE1) to achieve tumor cell-selective dual-mode imaging of microRNA. Compared with the traditional EDC strategy, the integrated design of AIO-EDN achieves autocatalytic signal amplification without extra fuel strands. Moreover, the AIO-EDN leverages an endogenous APE1 overexpressed in cancer cells to activate the EDC reaction, which, however, exerts no target sensing activity in normal cells. Combining fluorescence- and surface-enhanced Raman scattering (FL/SERS) dual-mode imaging techniques, this DNA nanomachine exhibits significantly improved accuracy and tumor cell selectivity for microRNA imaging in living cells. This study provides a new paradigm to develop an integrated EDC-based platform and shows great potential in in-depth cancer diagnosis with high precision.

Catalase-assembled nanoparticles for PA/CT dual-modality imaging and repair of acute alcoholic gastritis.

The development of simple, rapid, sensitive and noninvasive theranostic agents for acute gastritis is crucial. Herein, an engineering catalase-conjugated bismuth nanoparticle was fabricated for near-infrared photoacoustic imaging and computed tomography imaging of acute alcoholic gastritis. This nanoparticle could quickly respond to H2O2 and H+ overexpressed in the microenvironment of acute gastritis in mice, emitting strong signals for precise localization. Additionally, it adhered to the damaged gastric mucosa for an extended period, acting as a long-acting mucosal protector by inhibiting related inflammatory reactions and promoting mucosal repair. The use of this catalase-assembled nanoparticle could extend its residence time in the stomach, thereby reducing the drug dose and treatment duration. These findings of our study underscored the potential of this multifunctional nanoplatform for integrated diagnosis and treatment of gastrointestinal inflammatory diseases.

Carrier-free nanoparticles for cancer theranostics with dual-mode magnetic resonance imaging/fluorescence imaging and combination photothermal and chemodynamic therapy.

Both photothermal therapy (PTT) and chemodynamic therapy (CDT) are designed to focus their antitumor effect on only the tumor site, thereby minimizing unwanted severe damage to healthy tissue outside the tumor. However, each monotherapy is limited in achieving complete tumor eradication, resulting in tumor recurrence. The combination of multiple therapies may help to overcome the limitations of single therapy, improve the chances of complete tumor eradication, and reduce the risk of recurrence. Here, we report a novel multifunctional carrier-free nanoparticle, namely Mn-TPP@ICG, prepared through the self-assembly of ICG and 5,10,15,20-Tetraphenyl-21H,23H-porphine manganese (III) chloride (Mn-TPP). The prepared Mn-TPP@ICG allowed dual-mode imaging in the form of magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence imaging, as well as combination therapy in the form of CDT and PTT. In vitro experiments revealed that Mn-TPP@ICG nanoparticles can enable CDT by converting intratumoral hydrogen peroxide (H2O2) to highly cytotoxic hydroxyl radicals (·OH) and PTT through photothermal conversion, resulting in a strong synergistic antitumor effect. Furthermore, in vivo experiments revealed that CDT and PTT with Mn-TPP@ICG nanoparticles effected a synergistically enhanced therapeutic effect in 4 T1 tumor-bearing mice, significantly inhibiting tumor growth compared with monomodal treatments with no treatment, only CDT, or only PTT. Lastly, imaging experiments unveiled the exceptional capability of Mn-TPP@ICG nanoparticles in enabling fluorescence imaging and high-resolution MRI upon their intravenous administration. Thus, a meaningful carrier-free nanoparticle strategy for the synergistic combination of CDT and PTT was provided in our study, broadening the applications of nanotheranostics.

Dextran Sulfate-Modified and pH-Responsive Nanoprobes for Magnetic Resonance/Fluorescence Dual-Modality Imaging of Vulnerable Plaques.

Triggered by the vulnerability to atherosclerotic plaques, cardiovascular diseases (CVDs) have become a main reason for high mortality worldwide. Thus, there is an urgent need to develop functional molecular imaging modalities to improve the detection rate of vulnerable plaques. In this study, polyethyleneimine (PEI) was coated on the surface of mesoporous silica nanoprobes (MSN) loaded with Gd2O3 (MSN@Gd2O3), followed by coupling the fluorescent dye carboxylated heptamethine cyanine (IR808), and then the dextran sulfate (DS) was modified on the surface of MSN@Gd2O3@IR808 by electrostatic adsorption, to construct a targeted and pH-responsive magnetic resonance (MR)/near-infrared fluorescence imaging (NIRF) dual-modal nanoprobe (MSN@Gd2O3@IR808@DS nanoparticles). The nanoprobe presented a more concentrated distribution of spherical shapes in transmission electron microscopy. Invitro simulated vulnerable plaque microenvironment (pH = 5.5) presented significant T1-weighted imaging (T1WI) signal and longitudinal relaxation in the nanoprobe. Immunofluorescence staining and cellular uptake assays showed that MSN@Gd2O3@IR808@DS nanoparticles have the ability to specially bind to scavenger receptors A (SR-A). In vascular endothelium from the high-fat diet (HFD) New Zealand White rabbits, MSN@Gd2O3@IR808@DS nanoparticles can exhibit specific contrast-enhanced signals by MR/NIRF dual-modal imaging. In addition, cytotoxicity assays and hematoxylin and eosin (H&E) staining results demonstrated that MSN@Gd2O3@IR808@DS nanoparticles have good biocompatibility. Hence, this multifunctional MR/NIRF bimodal nanoprobe provides new experimental and technological ideas for the accurate diagnosis of vulnerable plaques.

Dimeric PD-L1 specific affibody grafted Fe-based nanosheets for tumor-targeting dual-mode magnet resonance imaging and enhancement of Photothermal-Immunotherapy

Dimeric PD-L1 specific affibody grafted Fe-based nanosheets for tumor-targeting dual-mode magnet resonance imaging and enhancement of Photothermal-Immunotherapy

Functional nanocrystal as effective contrast agents for dual-mode imaging: Live-cell sonoluminescence and contrast-enhanced echography.

In the context of molecular imaging, the present work explores an innovative platform made of lipid-coated nanocrystals as contrast-enhanced agent for both ultrasound imaging and sonoluminescence. At first, the dynamics of gas bubbles generation and cavitation under insonation with either pristine or lipid-coated nanocrystals (ZnO-Lip) are described, and the differences between the two colloidal systems are highlighted. These ZnO-Lip show an unprecedented ability to assist cavitation, which is reflected in enhanced sonoluminescent light emission with respect to the pristine nanocrystals or the pure water. Highly defined and sharp sonoluminescent images of cultured cells are indeed obtained, for the first time, when ZnO-Lip are used. Furthermore, ZnO-Lip were adopted as a nanosized agent for contrast-enhanced ultrasound imaging, i.e. echography, first in solutions, and then on ex-vivo tissues. A prolonged over time and bright imaging effect is observed when adopting the developed nanoparticles. Furthermore, their nanometric size and potential targeting with biomolecules would allow ease extravasation and tissue or even cell penetration, achieving enhanced-contrast imaging. Finally, the stimuli-responsive therapeutic applications of ZnO-Lip against tumors is overviewed, aiming to achieve a fully theranostic approach.

Photoacoustic and fluorescence dual-modality imaging of cerebral biomarkers in Alzheimer’s disease rodent model

Photoacoustic and fluorescence dual-modality imaging of cerebral biomarkers in Alzheimer’s disease rodent model

Quercetin-Loaded Melanin Nanoparticles Decorated with Collagenase Mediates Synergistic Immunomodulation and Restores Extracellular Matrix Homeostasis in Liver Fibrosis.

Liver fibrosis is a chronic disease that lacks effective drug treatment. Chronic damage and inflammation lead to the formation of collagen and fibrous scars. However, the excessive accumulation of collagen I significantly hinders the delivery of drugs into liver tissue. Therefore, this study developed a quercetin-loaded melanin nanoparticle codecorated collagenase (MNP-QUE-COL) for the treatment of liver fibrosis. These results showed that MNP-QUE-COL degraded excessive collagen I, thereby efficiently delivering melanin and quercetin into the liver tissue. MNP-QUE-COL exhibited optimal PA/MRI dual-mode imaging ability. In addition, the synergistic anti-inflammatory and reactive oxygen species scavenging function of quercetin and melanin was achieved by regulation of M1-M2 macrophage polarization and inhibition of pro-inflammatory cytokine release, reshaping the imbalanced extracellular interstitial inflammatory environment. The results of this research suggest that MNP-QUE-COL is a safe and efficient therapeutic nanoplatform for liver fibrosis, showing promise as a potential therapeutic strategy for liver fibrosis and associated diseases.

Correction to “X-ray-Irradiation-Induced Discoloration and Persistent Radioluminescence for Reversible Dual-Mode Imaging and Detection Applications”

Correction to “X-ray-Irradiation-Induced Discoloration and Persistent Radioluminescence for Reversible Dual-Mode Imaging and Detection Applications”

Functionalized Iron Oxide Nanoparticles for Both Dual-Modal Imaging and Erythropoiesis.

Cancer-related anemia (CRA), a complication of cancer, is considered the primary cause of high mortality for cancer patients. Safe and effective theranostics are desirable for realizing the high diagnostic accuracy of tumors and ameliorating CRA in the clinic. However, the available theranostics do not support dual-modal imaging and the amelioration of CRA at the same time. In this study, we synthesized functionalized iron oxide nanoparticles (Fe3O4 NPs) modified with protoporphyrin IX (PPIX) and folic acid (FA) by a one-step modification strategy (Fe3O4@NH-PPIX&FA NPs) or a step-by-step strategy (Fe3O4@NH-PPIX-FA NPs), aiming at both magnetic resonance imaging/fluorescence imaging (MRI/FI) and erythropoiesis. Fe3O4@NH-PPIX-FA NPs displayed better ability of MRI/FI than Fe3O4@NH-PPIX&FA NPs and had an efficient tumor targeting of 45 min after tail vein injection owing to the reduction of the steric effect and extension of FA groups. Fe3O4@NH-PPIX-FA NPs exhibited satisfactory erythropoiesis with up to 20% elevation of red blood cell (RBC) counts and hemoglobin concentrations in mice with CRA, which provided a safe alternative to RBC transfusions, especially for patients needing recurrent RBC transfusions. With excellent performance in both dual-modal imaging and erythropoiesis, Fe3O4@NH-PPIX-FA NPs could be a powerful tool for the theranostics of cancer patients with anemia.