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Pressure ulcers present a significant human and economic challenge, lacking a reliable method for early detection. To address this, we developed a system capable of early detection by using cooling stimulation and dynamic data acquisition techniques to monitor blood perfusion and skin temperature. The system consists of laser speckle perfusion imaging and thermal imaging. And we performed simulations to demonstrate that the system is capable of detect tissue damage across multiple layers, from superficial to deep. Testing on a rabbit ear model demonstrated that this approach, which combines dynamic perfusion and temperature parameters, effectively distinguishes early pressure ulcer areas from normal skin with a significant p value of 0.0015. This distinction was more precise compared to methods relying solely on static parameters or one parameter. Our study thereby offers a promising advancement in the proactive management and prevention of pressure ulcers. [ABSTRACT FROM AUTHOR]

The lanthanide complex, characterized by narrow emission bands, large Stokes shifts, long luminescence lifetime, robust resistance to photobleaching, and magnetic properties, affords significant promise for molecular imaging and biosensing applications. While most lanthanide complexes emitting visible light are extensively studied for cellular‐level detection and bioimaging, near‐infrared‐emitted (700–1700 nm) lanthanide compounds exhibit more favorable properties for bioimaging and biosensing, ascribed from deeper penetration and reduced bleaching effects. Besides, the magnetic lanthanide complex with higher magnetic resonance signals can enhance image resolution and sensitivity, offering more precise bioimaging analysis. However, the widespread use of high‐efficiency luminescence lanthanide complexes is currently impeded by the lack of design approaches for improving magnetic properties and sensitization chromophores with extended excitation and emission wavelengths. In this review, some fundamental theories and design strategies of lanthanide complexes are summarized for luminescence imaging, lifetime‐engineered imaging, magnetic resonance imaging, and dual‐modal imaging, and now highlight a selection of bioimaging and biosensing applications. The review addresses the existing gap in the literature by proposing some feasible approaches for improving the fluorescent and magnetic properties. Concurrently, future challenges and opportunities in the field of lanthanide complex probes are discussed. [ABSTRACT FROM AUTHOR]

Insufficient reactive oxygen species originating from hypoxia and high glutathione (GSH) in the tumor microenvironment (TME) is an important reason for radiotherapy (RT) resistance. Currently, radiosensitizers that remodel TME are widely investigated to enhance RT. However, developing an effective nano‐radiosensitization system that removes radiotherapy‐resistant factors from TME to boost RT effect while visualizing tumor imaging to aid therapy remains a challenge. Herein, MnO2 nanosheets are grown on the surface of ultrasmall Eu‐doped NaGdF4 (NaGdF4:Eu3+) nanoparticles and modified by biocompatible DSPE‐PEG2000 to prepare NaGdF4:Eu3+@MnO2@PEG nanoparticles (denoted as GMP NPs) as a radiosensitizer, which not only can reverse the TME by degrading H2O2 to produce oxygen and consuming high GSH but also achieve computed tomography (CT)and magnetic resonance (MR) imaging. When GMP NPs synergize with X‐ray, a better antitumor effect is achieved in both HeLa cells and tumor‐bearing mice, compared with X‐ray alone. In addition, both paramagnetic Mn2+ ionsproduced by decomposing MnO2 in TME and NaGdF4:Eu3+ nanoparticles enhance T1‐weighted MR imaging. NaGdF4:Eu3+ nanoparticles containing high atomic number of Gd/Eu effectively attenuate X‐ray to enhance CT imaging. The work provides new insights for developing an efficient RT sensitization platform integrating antitumor therapeutic effect as well as CT/MR dual‐modal imaging. [ABSTRACT FROM AUTHOR]

Insufficient reactive oxygen species originating from hypoxia and high glutathione (GSH) in the tumor microenvironment (TME) is an important reason for radiotherapy (RT) resistance. Currently, radiosensitizers that remodel TME are widely investigated to enhance RT. However, developing an effective nano‐radiosensitization system that removes radiotherapy‐resistant factors from TME to boost RT effect while visualizing tumor imaging to aid therapy remains a challenge. Herein, MnO2 nanosheets are grown on the surface of ultrasmall Eu‐doped NaGdF4 (NaGdF4:Eu3+) nanoparticles and modified by biocompatible DSPE‐PEG2000 to prepare NaGdF4:Eu3+@MnO2@PEG nanoparticles (denoted as GMP NPs) as a radiosensitizer, which not only can reverse the TME by degrading H2O2 to produce oxygen and consuming high GSH but also achieve computed tomography (CT)and magnetic resonance (MR) imaging. When GMP NPs synergize with X‐ray, a better antitumor effect is achieved in both HeLa cells and tumor‐bearing mice, compared with X‐ray alone. In addition, both paramagnetic Mn2+ ionsproduced by decomposing MnO2 in TME and NaGdF4:Eu3+ nanoparticles enhance T1‐weighted MR imaging. NaGdF4:Eu3+ nanoparticles containing high atomic number of Gd/Eu effectively attenuate X‐ray to enhance CT imaging. The work provides new insights for developing an efficient RT sensitization platform integrating antitumor therapeutic effect as well as CT/MR dual‐modal imaging.

Wan-Ling Liu,1– 4,* Yong-Qu Zhang,1– 5,* Xiang-Jie Luo,6 Yuan-Yuan Zhu,1– 4 Liang Song,7 Zi-He Ming,1– 4 Li-Xin Zhang,1– 4 Meng-Jun Li,1– 4 Rui-Chan Lv,8 Guo-Jun Zhang,1– 4,9,* Min Chen2– 4,* 1Department of Breast-Thyroid-Surgery and Cancer Center, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer, Xiang’an Hospital of Xiamen University, Xiamen, People’s Republic of China; 3Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiamen, People’s Republic of China; 4Xiamen Research Center of Clinical Medicine in Breast & Thyroid Cancers, Xiamen, People’s Republic of China; 5Department of Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 6College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, People’s Republic of China; 7Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences and Technology University, Xiamen, People’s Republic of China; 8Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, Shanxi, People’s Republic of China; 9Cancer Research Center, School of Medicine, Xiamen University, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Chen; Guo-Jun Zhang, Email mchen@xah.xmu.edu.cn; gjzhang@xah.xmu.edu.cnBackground: Durable responses to immune-checkpoint blocking therapy (ICT) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have improved outcomes for patients with triple negative breast cancer (TNBC). Unfortunately, only 19– 23% of patients benefit from ICT. Hence, non-invasive strategies evaluating responses to therapy and selecting patients who will benefit from ICT are critical issues for TNBC immunotherapy.Methods: We developed a novel nanoparticle-Atezolizumab (NPs-Ate) consisting of indocyanine green (ICG), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), human serum albumin (HSA), and Atezolizumab. The efficiency of Gd-DTPA linking was verified using mass spectrometry, and the size of NPs-Ate was characterized using Nano-flow cytometry. The synthesized NPs-Ate were evaluated for fluorescence stability, penetration depth, and target specificity. TNBC cell lines and tumor-bearing mice models were used to identify the feasibility of this dual-modal second near-infrared/magnetic resonance imaging (NIR-II/MRI) system. Additionally, ICT combination with chemotherapy or radiotherapy in TNBC tumor-bearing mice models were used to assess dynamic changes of PD-L1 and predicted therapeutic responses with NPs-Ate.Results: Atezolizumab, a monoclonal antibody, was successfully labeled with ICG and Gd-DTPA to generate NPs-Ate. This demonstrated strong fluorescence signals in our NIR-II imaging system, and relaxivity (γ 1) of 9.77 mM− 1 s− 1. In tumor-bearing mice, the NIR-II imaging signal background ratio (SBR) reached its peak of 11.51 at 36 hours, while the MRI imaging SBR reached its highest as 1.95 after 12 hours of tracer injection. NPs-Ate specifically targets cells and tumors expressing PD-L1, enabling monitoring of PD-L1 status during immunotherapy. Combining therapies led to inhibited tumor growth, prolonged survival, and increased PD-L1 expression, effectively monitored using the non-invasive NPs-Ate imaging system.Conclusion: The NIR-II/MRI NPs-Ate effectively reflected PD-L1 status during immunotherapy. Real-time and non-invasive immunotherapy and response/prognosis monitoring under NIR-II/MRI imaging guidance in TNBC is a promising and innovative technology with potential for extensive clinical applications in the future.Keywords: dual-modal imaging, triple-negative breast cancer, immune-checkpoint blocking therapy, programmed cell death protein ligand-1, monitoring therapeutic response

Abstract Background Uveal melanoma (UM) is adults’ most common primary intraocular malignant tumor, prone to metastasis and high mortality. Eyeball enucleation commonly used in the clinic will lead to permanent blindness and mental disorders. Thus, new methods are urgently needed to diagnose and treat UM early to preserve patients’ vision. Methods and results Herein, multifunctional nanoparticles (NPs) were synthesized by loading chlorin e6 (Ce6) in poly-lactic-co-glycolic acid (PLGA) NPs and wrapping FeIII-tannic acid (FeIII-TA) on the outside (FeIII-TA/PLGA/Ce6, designated as FTCPNPs). Then, the synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) antitumor effects of FTCPNPs excited by near-infrared (NIR) laser were evaluated. Moreover, we verified the mechanism of synergistic PTT/PDT leading to mitochondrial dysfunction and inducing tumor cell apoptosis. Additionally, FTCPNPs can be used as excellent magnetic resonance (MR)/photoacoustic (PA) imaging contrast agents, enabling imaging-guided cancer treatment. Finally, The NPs have good biological safety. Conclusion This noninvasive NIR light-triggered cooperative phototherapy can easily penetrate eye tissue and overcome the disadvantage of limited penetration of phototherapy. Therefore, cooperative phototherapy is expected to be used in fundus tumors. This treatment model is applied to UM for the first time, providing a promising strategy and new idea for integrating the diagnosis and treatment of UM.

Taking apart in numerous physiological and pathological activities, hydrogen sulfide (H2S) has been selected as an excellent target spot for the early diagnosis of cancer. So far, there are many mature probes that apply single optical imaging to monitor endogenous H2S. Nevertheless, a single modality is not an ideal method to afford accurate diagnostic information in comprehensive biological organisms. Herein, we developed a dual-modal imaging probe BWS. This designed probe showed a specific response to H2S with both chemiluminescence and NIR fluorescence light-up. The concurrence of fluorescence and chemiluminescence signal provided "double insurances" for highly accurate monitoring of H2S. Satisfactorily, this dual-modal imaging probe performed precise visualization of endogenous H2S in living cells and in vivo. We envisaged that this chemiluminescence/fluorescence real-time dual-modality strategy for H2S detection will expand and optimize the multimodal imaging methods for efficient diagnosis and treatment of cancer. [ABSTRACT FROM AUTHOR]

Background: Uveal melanoma (UM) is adults' most common primary intraocular malignant tumor, prone to metastasis and high mortality. Eyeball enucleation commonly used in the clinic will lead to permanent blindness and mental disorders. Thus, new methods are urgently needed to diagnose and treat UM early to preserve patients' vision. Methods and results: Herein, multifunctional nanoparticles (NPs) were synthesized by loading chlorin e6 (Ce6) in poly-lactic-co-glycolic acid (PLGA) NPs and wrapping FeIII-tannic acid (FeIII-TA) on the outside (FeIII-TA/PLGA/Ce6, designated as FTCPNPs). Then, the synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) antitumor effects of FTCPNPs excited by near-infrared (NIR) laser were evaluated. Moreover, we verified the mechanism of synergistic PTT/PDT leading to mitochondrial dysfunction and inducing tumor cell apoptosis. Additionally, FTCPNPs can be used as excellent magnetic resonance (MR)/photoacoustic (PA) imaging contrast agents, enabling imaging-guided cancer treatment. Finally, The NPs have good biological safety. Conclusion: This noninvasive NIR light-triggered cooperative phototherapy can easily penetrate eye tissue and overcome the disadvantage of limited penetration of phototherapy. Therefore, cooperative phototherapy is expected to be used in fundus tumors. This treatment model is applied to UM for the first time, providing a promising strategy and new idea for integrating the diagnosis and treatment of UM. [ABSTRACT FROM AUTHOR]

Accurate measurement of two-phase flow quantities is essential for managing production in many industries. However, the inherent complexity of two-phase flow often makes estimating these quantities difficult, necessitating the development of reliable techniques for quantifying two-phase flow. In this paper, we investigated the feasibility of using state estimation for dynamic image reconstruction in dual-modal tomography of two-phase oil–water flow. We utilized electromagnetic flow tomography (EMFT) to estimate velocity fields and electrical tomography (ET) to determine phase fraction distributions. In state estimation, the contribution of the velocity field to the temporal evolution of the phase fraction distribution was accounted for by approximating the process with a convection–diffusion model. The extended Kalman filter (EKF) and fixed-interval Kalman smoother (FIKS) were used to reconstruct the temporally evolving velocity and phase fraction distributions, which were further used to estimate the volumetric flow rates of the phases. Experimental results on a laboratory setup showed that the FIKS approach outperformed the conventional stationary reconstructions, with the average relative errors of the volumetric flow rates of oil and water being less than 4%. The FIKS approach also provided feasible uncertainty estimates for the velocity, phase fraction, and volumetric flow rate of the phases, enhancing the reliability of the state estimation approach. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) has become one of the most promising therapies in cancer treatment as its noninvasiveness, high selectivity, and favorable compliance in clinic. However, tumor thermotolerance and distal metastasis reduce its efficacy, becoming the bottleneck of applying PTT in clinic. In this study, a chidamide-loaded magnetic polypyrrole nanocomposite (CMPP) has been fabricated as a visualized cancer photothermal agent (PTA) to counter tumor thermotolerance and metastasis. The efficacy of CMPP was characterized by in vitro and in vivo assays. As a result, this kind of magnetic polypyrrole nanocomposites were black spherical nanoparticles, possessing a favorable photothermal effect and the suitable particle size of 176.97 ± 1.45 nm with a chidamide loading rate of 12.92 ± 0.45%. Besides, comparing with PTT, CMPP exhibited significantly higher cytotoxicity and cellular apoptosis rate in two tumor cell lines (B16-F10 and HepG2). In vivo study, the mice showed obvious near-infrared (NIR) and magnetic resonance imaging (MRI) dual-modal imaging at tumor sites and sentinel lymph nodes (SLNs); on the other hand, magnetic targeting guided CMPP achieved a cure level on melanoma-bearing mice through preventing metastasis and thermotolerance. Overall, with high loading efficiency of chidamide and strong magnetic targeting to tumor sites and SLNs, CMPP could significantly raise efficiency of PTT by targeting tumor thermotolerance and metastasis, and this strategy may be exploited therapeutically to upgrade PTT with MPP as one of appropriate carriers for histone deacetylase inhibitors (HDACis).

Retinoblastoma (RB) is a malignant intraocular neoplasm that occurs in children. Diagnosis and therapy are frequently delayed, often leading to metastasis, which necessitates effective imaging and treatment. In recent years, the use of nanoplatforms allowing both imaging and targeted treatment has attracted much attention. Herein, we report a novel nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal RB therapy. The dual-modal imaging capability, photothermal conversion under laser irradiation, biocompatibility, and antitumor ability of these liposomes were appraised. The multifunctional liposome showed a good tumor targeting ability and was efficacious as a dual-modality contrast agent both in vivo and in vitro. When laser-irradiated, the liposome converted light energy to heat. This action caused immediate destruction of tumor cells, while simultaneously initiating PFP phase transformation to release DOX, resulting in both photothermal and chemotherapeutic antitumor effects. Notably, the FA-DOX-ICG-PFP@Lip showed good biocompatibility and no systemic toxicity was observed after laser irradiation in RB tumor-bearing mice. Hence, the FA-DOX-ICG-PFP@Lip shows great promise for dual-modal imaging-guided chemo/photothermal therapy, and may have significant value for diagnosing and treating RB.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral and maxillofacial region. Due to its unique location, earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance. Herein, gadolinium-containing semiconductor polymer nanoparticles (SPN-Gd) were designed and prepared. The nanoparticles consist of a near-infrared (NIR) absorption semiconductor polymer (PCPDTBT) served as fluorescence signal source and a photothermal conversion agent (PTA) and a gadolinium-grafted triblock amphiphilic copolymer (F127-DTPA-Gd) served as a magnetic resonance imaging (MRI) contrast agent and nanocarrier. The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time, and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy (PTT). Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT. [ABSTRACT FROM AUTHOR]

Abstract The localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization have a number of limitations, such as invasive features of hookwires and microcoils, and rapid diffusion after injection of indocyanine green (ICG). Lanthanide-based metal–organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site.

Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy. [Display omitted] • A tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized. • Cy-Bio-GSH exhibits remarkable sensitivity and selectivity to glutathione (GSH). • Cy-Bio-GSH can visualize GSH in cells and differentiate normal and cancer cells. • The probe enhances synergistic PDT/PTT with good killing ability of cancer cells. • Cy-Bio-GSH with tumor-targeting ability makes the ablation of tumors in mice. [ABSTRACT FROM AUTHOR]

Abstract Background The overall survival rate of osteosarcoma (OS) patients has not been improved for 30 years, and the diagnosis and treatment of OS is still a critical issue. To improve OS treatment and prognosis, novel kinds of theranostic modalities are required. Molecular optical imaging and phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), are promising strategies for cancer theranostics that exhibit high imaging sensitivity as well as favorable therapeutic efficacy with minimal side effect. In this study, semiconducting polymer nanoparticles (SPN-PT) for OS-targeted PTT/PDT are designed and prepared, using a semiconducting polymer (PCPDTBT), providing fluorescent emission in the second near-infrared window (NIR-II, 1000 - 1700 nm) and photoacoustic (PA) signal in the first near-infrared window (NIR-I, 650 - 900 nm), served as the photosensitizer, and a polyethylene glycolylated (PEGylated) peptide PT, providing targeting ability to OS. Results The results showed that SPN-PT nanoparticles significantly accelerated OS-specific cellular uptake and enhanced therapeutic efficiency of PTT and PDT effects in OS cell lines and xenograft mouse models. SPN-PT carried out significant anti-tumor activities against OS both in vitro and in vivo. Conclusions Peptide-based semiconducting polymer nanoparticles permit efficient NIR-II fluorescence/NIR-I PA dual-modal imaging and targeted PTT/PDT for OS. Graphic Abstract

Abstract Indocyanine green (ICG) is a clinically approved dye that has shown great promise as a phototheranostic material with fluorescent, photoacoustic and photothermal responses in the near-infrared region. However, it has certain limitations, such as poor photostability and non-specific binding to serum proteins, subjected to rapid clearance and decreased theranostic efficacy in vivo. This study reports stable and biocompatible nanoparticles of ICG (ICG-Fe NPs) where ICG is electrostatically complexed with an endogenously abundant metal ion (Fe3+) and subsequently nanoformulated with a clinically approved polymer surfactant, Pluronic F127. Under near-infrared laser irradiation, ICG-Fe NPs were found to be more effective for photothermal temperature elevation than free ICG molecules owing to the improved photostability. In addition, ICG-Fe NPs showed the markedly enhanced tumor targeting and visualization with photoacoustic/fluorescent signaling upon intravenous injection, attributed to the stable metal complexation that prevents ICG-Fe NPs from releasing free ICG before tumor targeting. Under dual-modal imaging guidance, ICG-Fe NPs could successfully potentiate photothermal therapy of cancer by applying near-infrared laser irradiation, holding potential as a promising nanomedicine composed of all biocompatible ingredients for clinically relevant phototheranostics.

Abstract Background Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200–400 nm) and visible light (Vis, 400–650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000–1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. Results Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core–shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What’s more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. Conclusions The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision. Graphical abstract

Tumor microenvironment (TME)-activated theranostics is a promising strategy to effectively identify small lesions, improve antitumor efficacy, and reduce the risk of undesired side effects. Hypoxia, as a common characteristic of TME, can serve as a preferred site for stimulus-dependent activation; however, tumor-hypoxia levels in various developmental stages exhibit different characteristics, severely limiting the response sensitivity. Herein, a circulating self-reinforcing hypoxic nanoamplifier (CGH NAs) is developed that utilizes a dual-chain reaction process (internal regulation, internal regulation) to achieve precise activation of NIR-II FL/photoacoustic (PA) imaging-guided synergistic therapy. Inspired by the positive correlation of nitroreductase (NTR) with hypoxia, the CGH NAs encapsulate CQ4T and GOx into NTR-sensitive hyaluronic acid-nitroimidazole (HA-NI) shell via a self-assembly approach, enabling aggregation-caused NIR-II FL quenching and tumor-accurate delivery. When CGH NAs efficiently accumulated in the tumor region, the intensive local NTR reduced hydrophobic –NO2 to hydrophilic –NH2, which lead to disassembly of CGH NAs. The released GOx could consume O2 (internal regulation) and glucose to cut off the energy supply, inducing tumor-starvation therapy; generate gluconic acid and H2O2 (oxidative stress). Meanwhile, the released CQ4T promoted rapid recovery of NIR-II FL signals for imaging-guided PDT, which could simultaneously deplete intratumoral O2 (external stimulation). Remarkably, the strengthened tumor-hypoxia levels in turn accelerated the NTR-responsive degradation of the CGH NAs, thereby achieving high-efficiency theranostic.

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O2 generation by catalyzing tumor over-expressed H2O2, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.

The mechanical and electrical properties of soft tissues are relative to soft tissues’ pathological state. Modern medical imaging devices have shown a trend to multi-modal imaging, which will provide complementary functional information to improve the accuracy of disease diagnosis. However, no method or system can simultaneously measure the mechanical and electrical properties of the soft tissue. In this study, we proposed a novel dual-modal imaging method integrated by shear wave elasticity imaging (SWEI) and Magneto-acousto-electrical tomography (MAET) to measure soft tissue's elasticity and conductivity simultaneously. A dual-modal imaging system based on a linear array transducer is built, and the imaging performances of MAET and SWEI were respectively evaluated by phantoms experiment and in vitro experiment. Conductivity phantom experiments show that the MAET in this dual-modal system can image conductivity gradient as low as 0.4 S/m. The phantom experiments show that the reconstructed 2-D elasticity maps of the phantoms with inclusions with a diameter larger than 5 mm are relatively accurate. In vitro experiments show that the elasticity parameter can significantly distinguish the changes in tissue before and after heating. This study first proposes a method that can simultaneously obtain tissue elasticity and electrical conductivity to the best of our knowledge. Although this paper just carried out the proof of concept experiments of the new method, it demonstrates great potential for disease diagnosis in the future. [ABSTRACT FROM AUTHOR]

Accurate measurement of two-phase flow quantities is essential for managing production in many industries. However, the inherent complexity of two-phase flow often makes estimating these quantities difficult, necessitating the development of reliable techniques for quantifying two-phase flow. In this paper, we investigated the feasibility of using state estimation for dynamic image reconstruction in dual-modal tomography of two-phase oil–water flow. We utilized electromagnetic flow tomography (EMFT) to estimate velocity fields and electrical tomography (ET) to determine phase fraction distributions. In state estimation, the contribution of the velocity field to the temporal evolution of the phase fraction distribution was accounted for by approximating the process with a convection–diffusion model. The extended Kalman filter (EKF) and fixed-interval Kalman smoother (FIKS) were used to reconstruct the temporally evolving velocity and phase fraction distributions, which were further used to estimate the volumetric flow rates of the phases. Experimental results on a laboratory setup showed that the FIKS approach outperformed the conventional stationary reconstructions, with the average relative errors of the volumetric flow rates of oil and water being less than 4%. The FIKS approach also provided feasible uncertainty estimates for the velocity, phase fraction, and volumetric flow rate of the phases, enhancing the reliability of the state estimation approach.

We propose a high-speed all-optic dual-modal system that integrates spectral-domain optical coherence tomography and photoacoustic microscopy (PAM). A 3 ∗ 3 coupler-based interferometer is used to remotely detect the surface vibration caused by photoacoustic (PA) waves. Three outputs of the interferometer are acquired simultaneously with a multi-channel data acquisition card. One channel data with the highest PA signal detection sensitivity is selected for sensitivity compensation. Experiment on the phantom demonstrates that the proposed method can successfully compensate for the loss of intensity caused by sensitivity variation. The imaging speed of the PAM is improved compared to our previous system. The total time to image a sample with 2 5 6 × 2 5 6 pixels is ∼ 2 0 s. Using the proposed system, the microvasculature in the mouse auricle is visualized and the blood flow state is accessed. [ABSTRACT FROM AUTHOR]

In consideration of deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-modal probes are much more desirable. However, dual-modal imaging of gastritis using molecular probes remains a challenge due to the harsh gastric acid environment in the stomach. Based on the positive correlation between gastritis and cell viscosity, stomach acid-stable and viscosity-activated probes could potentially diagnose gastritis. As a proof of concept, herein, a fluorescent and photoacoustic dual-modal probe (named WSP-1) is revealed for the imaging of drug-induced acute gastritis in vivo. WSP-1 exhibits viscosity-dependent fluorescence emission and photoacoustic signals. A rotatable C–C single bond is incorporated into the D-π-A structure of WSP-1, which could facilitate the formation of the twisted intramolecular charge transfer (TICT) state in a low-viscosity environment (weak fluorescence/PA signal) and the intramolecular charge transfer (ICT) state in a high-viscosity environment (strong fluorescence/PA signal). WSP-1 has demonstrated the capability to target mitochondria and can be utilized to monitor the viscosity enhancement of cells during inflammation. Most importantly, WSP-1 exhibits good optical and structural stability in gastric acid. By leveraging these desirable features of WSP-1, we have achieved fluorescent and 3 D photoacoustic in situ imaging of drug-induced acute gastritis following oral administration of WSP-1. [Display omitted] • A new fluorescent and photoacoustic (PA) dual-modal probe was revealed. • The probe was structurally optimized with molecular engineering methods. • The dual-modal responses were illustrated with theoretical calculations. • Ultra-high structural-stability and photo-stability in stomach acid. • Dual-mode in vivo and in situ 3 D imaging of gastritis with good fidelity. [ABSTRACT FROM AUTHOR]

We propose a high-speed all-optic dual-modal system that integrates spectral-domain optical coherence tomography and photoacoustic microscopy (PAM). A [Formula: see text] coupler-based interferometer is used to remotely detect the surface vibration caused by photoacoustic (PA) waves. Three outputs of the interferometer are acquired simultaneously with a multi-channel data acquisition card. One channel data with the highest PA signal detection sensitivity is selected for sensitivity compensation. Experiment on the phantom demonstrates that the proposed method can successfully compensate for the loss of intensity caused by sensitivity variation. The imaging speed of the PAM is improved compared to our previous system. The total time to image a sample with [Formula: see text] pixels is [Formula: see text][Formula: see text]s. Using the proposed system, the microvasculature in the mouse auricle is visualized and the blood flow state is accessed.

Photoacoustic imaging can be used to extract functional information at the molecular level for imaging the whole body of small animals in vivo. However, the use of a mechanical scanner to image the whole body involves acquiring the data for a period of time which can lead to breathing-related artifacts. Thus, the acquired three-dimensional data cannot be analyzed and visualized using two-dimensional projection rendering techniques unless the respiratory distortions are minimized. In this study, an ultrasound-guided breath-compensation method for the three-dimensional data of photoacoustic macroscopy to facilitate visualization and analysis in the depth direction is presented. Photoacoustic and ultrasound data of the whole body of mice were acquired in vivo, then the distorted skin layers were compensated in ultrasound data. The extracted distortion parameters were then applied to the corresponding photoacoustic data to compensate for the motion. The compensation method was successfully applied to visualize three-dimensional hemoglobin oxygen saturation in the whole body of mice in vivo by using multispectral photoacoustic data. The resulting three-dimensional images show that the developed methodology can be used in various biomedical studies, including monitoring drug delivery, imaging of tumors, and analysis of vasculature networks.

Abstract Background Sonodynamic therapy (SDT) is an emerging non-invasive therapeutic technique. SDT-based cancer therapy strategies are presently underway, and it may be perceived as a promising approach to improve the efficiency of anti-cancer treatment. In this work, multifunctional theranostic nanoparticles (NPs) were synthesized for synergistic starvation therapy and SDT by loading glucose oxidase (GOx, termed G) and 5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (T (p-Cl) PPMnCl, termed PMnC) in Poly (lactic-co-glycolic) acid (PLGA) NPs (designated as MG@P NPs). Results On account of the peroxidase-like activity of PMnC, MG@P NPs can catalyze hydrogen peroxide (H2O2) in tumor regions to produce oxygen (O2), thus enhancing synergistic therapeutic effects by accelerating the decomposition of glucose and promoting the production of cytotoxic singlet oxygen (1O2) induced by ultrasound (US) irradiation. Furthermore, the NPs can also serve as excellent photoacoustic (PA)/magnetic resonance (MR) imaging contrast agents, effectuating imaging-guided cancer treatment. Conclusion Multifunctional MG@P NPs can effectuate the synergistic amplification effect of cancer starvation therapy and SDT by hypoxia modulation, and act as contrast agents to enhance MR/PA dual-modal imaging. Consequently, MG@P NPs might be a promising nano-platform for highly efficient cancer theranostics. Graphical Abstract

[Display omitted] Most nanomedicines with suitable sizes (normally 100–200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors. To this end, a near-infrared light (NIR) −triggered size-shrinkable micelle system (Fe 3 O 4 @AuNFs/DOX-M) coloaded antitumor drug doxorubicin (DOX) and biomodal imaging agent magnetic gold nanoflower (Fe 3 O 4 @AuNFs) was developed to achieve efficient theranostic of tumors. Upon the accumulation of Fe 3 O 4 @AuNFs/DOX-M in the tumor periphery, a NIR laser was irradiated near the tumor sites, and the loaded Fe 3 O 4 @Au NFs could convert the light energy to heat, which triggered the cleavage of DOX-M to the ultra-small micelles (∼5 nm), thus realizing the deep penetration of micelles and on-demand drug release. Moreover, Fe 3 O 4 @AuNFs in the micelles could also be used as CT/MRI dual-modal contrast agent to "visualize" the tumor. Up to 92.6 % of tumor inhibition was achieved for the developed Fe 3 O 4 @AuNFs/DOX-M under NIR irradiation. This versatile micelle system provided a promising drug carrier platform realizing efficient tumor dual-modal diagnosis and photothermal-chemotherapy integration. [ABSTRACT FROM AUTHOR]

While Electrical Impedance Tomography (EIT) has found many biomedicine applications, better image quality is needed to provide quantitative analysis for tissue engineering and regenerative medicine. This paper reports an impedance-optical dual-modal imaging framework that primarily targets at high-quality 3D cell culture imaging and can be extended to other tissue engineering applications. The framework comprises three components, i.e., an impedance-optical dual-modal sensor, the guidance image processing algorithm, and a deep learning model named multi-scale feature cross fusion network (MSFCF-Net) for information fusion. The MSFCF-Net has two inputs, i.e., the EIT measurement and a binary mask image generated by the guidance image processing algorithm, whose input is an RGB microscopic image. The network then effectively fuses the information from the two different imaging modalities and generates the final conductivity image. We assess the performance of the proposed dual-modal framework by numerical simulation and MCF-7 cell imaging experiments. The results show that the proposed method could improve the image quality notably, indicating that impedance-optical joint imaging has the potential to reveal the structural and functional information of tissue-level targets simultaneously. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted dual-modal imaging agents for whole body PET/SPECT imaging and fluorescence-guided surgery (FGS) have significant potential to improve surgical workflow. Here we present an overview of key design considerations and fluorescent building blocks, along with potential future directions in this exciting field. Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal agents is a chemical challenge and a topic of ongoing research. In this review, we define key design considerations of targeted dual-modal imaging from a topological perspective, list targeted dual-modal probes disclosed in the last decade, review recent progress in the field of NIR fluorescent probe development, and highlight future directions in this rapidly developing field. [ABSTRACT FROM AUTHOR]

The localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization have a number of limitations, such as invasive features of hookwires and microcoils, and rapid diffusion after injection of indocyanine green (ICG). Lanthanide-based metal–organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site. [ABSTRACT FROM AUTHOR]

Dongdong Zheng,1,* Caifeng Wan,1,* Hong Yang,2 Li Xu,1 Qi Dong,1 Chengrun Du,3 Jing Du,1 Fenghua Li1 1Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2College of Chemistry and Materials Science, Shanghai Normal University, Shanghai, People’s Republic of China; 3Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Du; Fenghua Li Email beautydujing@163.com; fenghua-li@163.comPurpose: The treatment of breast cancer is often ineffective due to the protection of the tumor microenvironment and the low immunogenicity of tumor cells, leading to a poor therapeutic effect. In this study, we designed a nano-theranostic platform for these obstacles: a photothermal effect mediated by a gold shell could remodel the tumor microenvironment by decreasing cancer-associated fibroblasts (CAFs) and promote the release of doxorubicin (DOX) from nanoparticles. In addition, it could realize photoacoustic (PA)/MRI dual-model imaging for diagnose breast cancer and targeted identification of Her2-positive breast cancer.Methods: Her2-DOX-superparamagnetic iron oxide nanoparticles (SPIOs)@Poly (D, L-lactide-co-glycolide) acid (PLGA)@Au nanoparticles (Her2-DSG NPs) were prepared based on a single emulsion oil-in-water (O/W) solvent evaporation method, gold seed growing method, and carbon diimide method. The size distribution, morphology, PA/MRI imaging, drug loading capacity, and drug release were investigated. Cytotoxicity, antitumor effect, cellular uptake, immunogenic cell death (ICD) effect, and targeted performance on human Her2-positive BT474 cell line were investigated in vitro. BT474/Adr cells were constructed and the antitumor effect of NPs on it was evaluated in vitro. Moreover, chemical-photothermal therapy effect, PA/MRI dual-model imaging, ICD effect induced by NPs, and tumor microenvironment remodeling in human BT474 breast cancer nude mice model were also investigated.Results: Nanoparticles were spherical, uniform in size and covered with a gold shell. NPs had a photothermal effect, and can realize photothermal-controlled drug release in vitro. Chemical-photothermal therapy had a good antitumor effect on BT474/Adr cells and on BT474 cells in vitro. The targeting evaluation in vitro showed that Her2-DSG NPs could actively target and identify Her2-positive tumor cells. The PA/MRI imaging was successfully validated in vitro/vivo. Similarly, NPs could enhance the ICD effect in vitro/vivo, which could activate an immune response. Immunofluorescence results also proved that photothermal effect could decrease CAFs to remodel the tumor microenvironment and enhance the accessibility of NPs to tumor cells. According to the toxicity results, targeted drug delivery combined with photothermal-responsive drug release proved that NPs had good biosafety in vivo. Chemical-photothermal therapy of Her2-targeted NPs has a good antitumor effect in the BT474 nude mice model.Conclusion: Our study showed that chemical-photothermal therapy combined with tumor microenvironment remodeling and immune activation based on the Her2-DSG NPs we developed are very promising for Her2-positive breast cancer.Keywords: tumor microenvironment remodeling, chemoimmunotherapy, photothermal effect, targeted nano-theranostic platform, dual-modal imaging

Background: The overall survival rate of osteosarcoma (OS) patients has not been improved for 30 years, and the diagnosis and treatment of OS is still a critical issue. To improve OS treatment and prognosis, novel kinds of theranostic modalities are required. Molecular optical imaging and phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), are promising strategies for cancer theranostics that exhibit high imaging sensitivity as well as favorable therapeutic efficacy with minimal side effect. In this study, semiconducting polymer nanoparticles (SPN-PT) for OS-targeted PTT/PDT are designed and prepared, using a semiconducting polymer (PCPDTBT), providing fluorescent emission in the second near-infrared window (NIR-II, 1000 - 1700 nm) and photoacoustic (PA) signal in the first near-infrared window (NIR-I, 650 - 900 nm), served as the photosensitizer, and a polyethylene glycolylated (PEGylated) peptide PT, providing targeting ability to OS. Results: The results showed that SPN-PT nanoparticles significantly accelerated OS-specific cellular uptake and enhanced therapeutic efficiency of PTT and PDT effects in OS cell lines and xenograft mouse models. SPN-PT carried out significant anti-tumor activities against OS both in vitro and in vivo. Conclusions: Peptide-based semiconducting polymer nanoparticles permit efficient NIR-II fluorescence/NIR-I PA dual-modal imaging and targeted PTT/PDT for OS. [ABSTRACT FROM AUTHOR]

High‐dimensional imaging mass cytometry (IMC) enables simultaneous quantification of over 35 biomarkers on one tissue section. However, its limited resolution and ultralow acquisition speed remain major issues for general clinical application. Meanwhile, conventional immunofluorescence microscopy (IFM) allows sub‐micrometer resolution and rapid identification of the region of interest (ROI), but only operates with low multiplicity. Herein, a series of lanthanide‐doped blue‐, green‐, and red‐fluorescent carbon nanodots (namely, B‐Cdots(Ln1), G‐Cdots(Ln2), and R‐Cdots(Ln3)) as fluorescence and mass dual‐modal tags are developed. Coupled with aptamers, B‐Cdots(159Tb)‐A10‐3.2, G‐Cdots(165Ho)‐AS1411, and R‐Cdots(169Tm)‐SYL3C dual‐functional aptamer probes, which are then multiplexed with commercially available Maxpar metal‐tagged antibodies for analyzing clinical formalin‐fixed, paraffin‐embedded (FFPE) prostatic adenocarcinoma (PaC) tissue, are further synthesized. The rapid identification of ROI with IFM using fluorescence signals and subsequent multiplexed detection of in situ ROI with IMC using the same tissue section is demonstrated. Dual‐modal probes save up to 90% IMC blind scanning time for a standard 3.5 mm × 3.5 mm overall image. Meanwhile, the IFM provides refined details and topological spatial distributions for the functional proteins at optical resolution, which compensates for the low resolution of the IMC imaging. [ABSTRACT FROM AUTHOR]

Background: Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200–400 nm) and visible light (Vis, 400–650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000–1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. Results: Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core–shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What's more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. Conclusions: The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) is a clinically approved dye that has shown great promise as a phototheranostic material with fluorescent, photoacoustic and photothermal responses in the near-infrared region. However, it has certain limitations, such as poor photostability and non-specific binding to serum proteins, subjected to rapid clearance and decreased theranostic efficacy in vivo. This study reports stable and biocompatible nanoparticles of ICG (ICG-Fe NPs) where ICG is electrostatically complexed with an endogenously abundant metal ion (Fe3+) and subsequently nanoformulated with a clinically approved polymer surfactant, Pluronic F127. Under near-infrared laser irradiation, ICG-Fe NPs were found to be more effective for photothermal temperature elevation than free ICG molecules owing to the improved photostability. In addition, ICG-Fe NPs showed the markedly enhanced tumor targeting and visualization with photoacoustic/fluorescent signaling upon intravenous injection, attributed to the stable metal complexation that prevents ICG-Fe NPs from releasing free ICG before tumor targeting. Under dual-modal imaging guidance, ICG-Fe NPs could successfully potentiate photothermal therapy of cancer by applying near-infrared laser irradiation, holding potential as a promising nanomedicine composed of all biocompatible ingredients for clinically relevant phototheranostics. [ABSTRACT FROM AUTHOR]

Haibin Guo,* Yanqing Xia,* Ke Feng, Xiaowei Qu, Cuilian Zhang, Feng Wan Henan Provincial People’s Hospital, Henan Provincial Reproductive Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Wan; Cuilian ZhangHenan Provincial People’s Hospital, Henan Provincial Reproductive Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of ChinaTel +86 371 87160762Email fengwanscholar@163.com; zhangcuilian@henu.edu.cnBackground: Metal–organic frameworks (MOFs) have attracted intensive research interest in the biomedical field because of their unique properties. However, in order to realize the high loading capacity and therapeutic efficacy, it is still urgent to develop a multifunctional MOFs-based nanoplatform.Materials and Methods: Herein, a pH/near-infrared (NIR) dual-responsive drug delivery system based on zeolitic imidazolate framework-8 (ZIF-8) is constructed for synergistic chemo-photothermal therapy and dual-modal magnetic resonance (MR)/photoacoustic (PA) imaging. The doxorubicin hydrochloride (DOX) is embedded into ZIF-8 through one-pot method, and the resultant ZIF-8/DOX is then successively modified with polydopamine, Mn ions and poly(ethylene glycol). The obtained ZIF-8/DMPP is systematically characterized, and both its in vitro and in vivo biological effects are evaluated in detail.Results: The ZIF-8/DMPP possesses a high drug-loading content of 18.9% and displays appropriate size and morphology. The pH-dependent degradation and drug release behavior of prepared ZIF-8/DMPP are confirmed. Importantly, the results demonstrate that the photothermal effect of ZIF-8/DMPP under NIR laser irradiation can significantly accelerate its drug releasing rate, further improving the intracellular drug concentrations. Thereafter, the augmented chemotherapeutic efficiency by photothermal effect against cancer cells is verified both in vitro and in vivo. Besides, the favorable MR and PA imaging capacity of ZIF-8/DMPP is also evidenced on the tumor model.Conclusion: Taken together, the surface engineering of ZIF-8-based nanocarrier in this work offers a promising strategy for the multifunctional MOFs-based drug delivery system.Keywords: zeolitic imidazolate framework-8, pH/NIR responsive, chemo-photothermal therapy, dual-modal imaging

Huikang Yang,1,* Yufang He,1,* Yan Wang,2,* Ruimeng Yang,1 Nianhua Wang,1 Li-Ming Zhang,3,* Meng Gao,4 Xinqing Jiang1 1Department of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province 510640, People’s Republic of China; 2Department of Urology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province 510640, People’s Republic of China; 3School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong Province 510275, People’s Republic of China; 4National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong Province 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinqing JiangDepartment of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Yuexiu District, Guangzhou, Guangdong Province 510640, People’s Republic of ChinaTel/Fax +86 13802961338Email eyjiangxq@scut.edu.cnMeng GaoNational Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Tianhe District, Guangzhou, Guangdong Province 510006, People’s Republic of ChinaTel/Fax +86 15521393090Email msmgao@scut.edu.cnIntroduction: Advanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ϵ-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT).Materials and Methods: The amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ϵ-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning.Results: The resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation.Discussion: This work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.Keywords: aggregation-induced emission, MR imaging, dual-modal imaging, photodynamic therapy

Abstract High‐dimensional imaging mass cytometry (IMC) enables simultaneous quantification of over 35 biomarkers on one tissue section. However, its limited resolution and ultralow acquisition speed remain major issues for general clinical application. Meanwhile, conventional immunofluorescence microscopy (IFM) allows sub‐micrometer resolution and rapid identification of the region of interest (ROI), but only operates with low multiplicity. Herein, a series of lanthanide‐doped blue‐, green‐, and red‐fluorescent carbon nanodots (namely, B‐Cdots(Ln1), G‐Cdots(Ln2), and R‐Cdots(Ln3)) as fluorescence and mass dual‐modal tags are developed. Coupled with aptamers, B‐Cdots(159Tb)‐A10‐3.2, G‐Cdots(165Ho)‐AS1411, and R‐Cdots(169Tm)‐SYL3C dual‐functional aptamer probes, which are then multiplexed with commercially available Maxpar metal‐tagged antibodies for analyzing clinical formalin‐fixed, paraffin‐embedded (FFPE) prostatic adenocarcinoma (PaC) tissue, are further synthesized. The rapid identification of ROI with IFM using fluorescence signals and subsequent multiplexed detection of in situ ROI with IMC using the same tissue section is demonstrated. Dual‐modal probes save up to 90% IMC blind scanning time for a standard 3.5 mm × 3.5 mm overall image. Meanwhile, the IFM provides refined details and topological spatial distributions for the functional proteins at optical resolution, which compensates for the low resolution of the IMC imaging.

Diagnosing of lymph node metastasis is challenging sometimes, and multimodal imaging offers a promising method to improve the accuracy. This work developed porphyrin-based nanoparticles ( 68 Ga-F127-TAPP/TCPP(Mn) NPs) as PET/MR dual-modal probes for lymph node metastasis imaging by a simple self-assembly method. Compared with F127-TCPP(Mn) NPs, F127-TAPP/TCPP(Mn) NPs synthesized by amino-porphyrins (TAPP) doping can not only construct PET/MR bimodal probes but also improve the T 1 relaxivity (up to 456%). Moreover, T 1 relaxivity can be adjusted by altering the molar ratio of TAPP/TCPP(Mn) and the concentration of F127. However, a similar increase in T 1 relaxivity was not observed in the F127-TCPP/TCPP(Mn) NPs, which were synthesized using carboxy-porphyrins (TCPP) doping. In a breast cancer lymph node metastasis mice model, subcutaneous injection of 68 Ga-F127-TAPP/TCPP(Mn) NPs through the hind foot pad, the normal lymph nodes and metastatic lymph nodes were successfully distinguished based on the difference of PET standard uptake values and MR signal intensities. Furthermore, the dark brown F127-TAPP/TCPP(Mn) NPs demonstrated the potential for staining and mapping lymph nodes. This study provides valuable insights into developing and applying PET/MR probes for lymph node metastasis imaging.

[Display omitted] As a promising noninvasive tumor treatment modality, dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has drawn extensive research interest in imaging-guided synergistic antitumor treatment. However, developing a high-efficient phototherapeutic agent is still a huge challenge, since single photosensitizer often suffers from the insufficient photothermal conversion efficiency (PCE) or low reactive oxygen species (ROS) productivity. Moreover, the overexpression of reductive glutathione (GSH) in tumor cells also severely compromises PDT efficiency. Here, inspired by the glutathione oxidase activity of high-valent transition metal ions, we designed a copper-coordinated nanotheranostic (PhA@NanoICG) by the coordination-driven co-assembly of photothermal-agent indocyanine green (ICG) and photodynamic-agent pheophorbide A (PhA), in which Cu2+ acted as a bridge to tightly associate ICG with PhA. Such carrier-free metal-coordinated nanotheranostics exhibited ultra-high dual-photosensitizers co-loading (~96.74 wt%) and excellent structural stability. Notably, NanoICG significantly increase the PCE of ICG via J-aggregation induced UV–vis absorption red-shift. Once PhA@NanoICG accumulated in tumor sites, they could be disassembled triggered by the weakly acidic and highly reducible tumor microenvironment. Moreover, the Cu2+ can deplete intracellular GSH and impair cellular antioxidant defense system, reducing the unnecessary ROS consumption caused by glutathione. Under fluorescence/photoacoustic imaging-guided laser irradiation, local hyperthermia and ROS were generated to induce tumor cells apoptosis. The in vitro and in vivo experiments consistently confirm that PhA@NanoICG could induce remarkable tumor inhibition through self-enhanced PTT and PDT, which may pave a new way for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Sonodynamic therapy (SDT) is an emerging non-invasive therapeutic technique. SDT-based cancer therapy strategies are presently underway, and it may be perceived as a promising approach to improve the efficiency of anti-cancer treatment. In this work, multifunctional theranostic nanoparticles (NPs) were synthesized for synergistic starvation therapy and SDT by loading glucose oxidase (GOx, termed G) and 5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (T (p-Cl) PPMnCl, termed PMnC) in Poly (lactic-co-glycolic) acid (PLGA) NPs (designated as MG@P NPs). Results: On account of the peroxidase-like activity of PMnC, MG@P NPs can catalyze hydrogen peroxide (H2O2) in tumor regions to produce oxygen (O2), thus enhancing synergistic therapeutic effects by accelerating the decomposition of glucose and promoting the production of cytotoxic singlet oxygen (1O2) induced by ultrasound (US) irradiation. Furthermore, the NPs can also serve as excellent photoacoustic (PA)/magnetic resonance (MR) imaging contrast agents, effectuating imaging-guided cancer treatment. Conclusion: Multifunctional MG@P NPs can effectuate the synergistic amplification effect of cancer starvation therapy and SDT by hypoxia modulation, and act as contrast agents to enhance MR/PA dual-modal imaging. Consequently, MG@P NPs might be a promising nano-platform for highly efficient cancer theranostics. [ABSTRACT FROM AUTHOR]

The low spatial resolution of Electrical Impedance Tomography (EIT) makes it challenging to conduct quantitative analysis of the electrical properties of imaging targets in biomedical applications. We in this paper propose to integrate optical imaging into EIT to improve EIT image quality and report a dual-modal image reconstruction algorithm based on optical image-guided group sparsity (IGGS). IGGS receives an RGB microscopic image and EIT measurements as inputs, extracts the structural features of conductivity distribution from optical images and fuses the information from the two imaging modalities to generate a high-quality conductivity image. The superior performance of IGGS is verified by numerical simulation and real-world experiments. Compared with selected single-modal EIT image reconstruction algorithms, i.e., the classical Tikhonov regularization and the state-of-the-art Structure-Aware Sparse Bayesian Learning and Enhanced Adaptive Group Sparsity with Total Variation, the proposed method presents superiorities in terms of shape preservation, background noise suppression, and differentiation of conductivity contrasts. [ABSTRACT FROM AUTHOR]

Dual‐modal imaging can integrate the advantages of different imaging technologies, which could improve the accuracy and efficiency of clinical diagnosis. Herein, a novel amphiphilic thermal‐responsive copolymer obtained from three types of monomers, N‐isopropyl acrylamide, 2‐(acetoacetoxy) ethyl methacrylate, and propargyl methacrylate, by RAFT copolymerization, is reported. It can be grafted with β‐cyclodextrin and aggregation‐induced emission (AIE) luminogens tetraphenylethylene by click chemistry and Biginelli reaction. The multifunctional supramolecular polymer (P4) can be constructed by host–guest inclusion between the copolymer and the Gd‐based contrast agent (CA) modified by adamantane [Ad‐(DOTA‐Gd)]. And it can form vesicles with a bilayer structure in aqueous which will enhance the AIE and magnetic resonance imaging effects. As fluorescent thermometer, P4 can enter HeLa cells for intracellular fluorescence imaging (FI) and is sensitive to temperature with detection limit value of 1.5 °C. As magnetic resonance CA, P4 exhibits higher relaxation compared to Magnevist, which can prolong the circulation time in vivo. In addition, Gd3+ in the polymer can be quickly released from the body by disassembly that reduced the biological toxicity. This work introduces new synthetic ideas for dual‐modal probe, which has great potential for clinical diagnostic applications in bioimaging. [ABSTRACT FROM AUTHOR]

Mechanoluminescence (ML) is one of the most important routes to realize remote sensing of stress distribution, but has never been used in temperature sensing. Traditionally, stress sensing and temperature sensing are separately realized through different methods in multifunctional sensors, which definitely makes the structure more complicated. In this work, the remote stress–temperature dual‐modal sensing is proposed by using the double‐lanthanide‐activated ML material SrZnSO:Tb,Eu, where the stress is read by the integral intensity of ML and the temperature is displayed by the green to red emission ratio (ITb/IEu) of ML in one material. The dual sensing mode in SrZnSO:Tb,Eu enables building of a new imaging system, providing a facile, reliable, and more sensitive way to remotely visualize the distribution of stress and temperature. It opens up a novel approach to develop advanced artificial skins with simplified structures in human–machine interfaces, structural health monitoring, and biomedical engineering applications. [ABSTRACT FROM AUTHOR]

As a molecular imaging modality, photoacoustic (PA) imaging has been in the spotlight because it can provide an optical contrast image of physiological information and a relatively deep imaging depth. However, its sensitivity is limited despite the use of exogenous contrast agents due to the background PA signals generated from nontargeted absorbers, such as blood and boundaries between different biological tissues. In addition, clutter artifacts generated in both in-plane and out-of-plane imaging region degrade the sensitivity of PA imaging. We propose a method to eliminate the nontargeted PA signals. For this study, we used a dual-modal ultrasound (US)-PA contrast agent that is capable of generating both the backscattered US and PA signals in response to the transmitted US and irradiated light, respectively. The US images of the contrast agents are used to construct a masking image that contains the location information about the target site and is applied to the PA image acquired after contrast agent injection. In vitro and in vivo experimental results demonstrated that the masking image constructed using the US images makes it possible to completely remove nontargeted PA signals. The proposed method can be used to enhance the clear visualization of the target area in PA images. [ABSTRACT FROM AUTHOR]

Objectives: Au nanoclusters (AuNCs) have been used widely in fluorescence bio‐imaging because of their good fluorescence, small particle size and non‐cytotoxicity. AuNCs are also efficient in computed tomography (CT) imaging. Hence, a dual‐modal imaging probe can be constructed without any complicated modification processes by exploiting the excellent performance of AuNCs. In the present study, AuNCs were enriched with mesoporous silica nanoparticles (MSNs) to obtain enhanced fluorescence/CT dual‐modal imaging, which was capable of acquiring more imaging information for diseases compared with single‐mode imaging. Materials and methods: Biocompatible bovine serum albumin (BSA)‐capped AuNCs were prepared and loaded into amine‐functionalized MSNs to form MSN@AuNCs. BSA‐AuNCs, MSNs, and MSN@AuNCs were characterized by ultraviolet‐visible (UV‐vis) spectra, transmission electron microscopy (TEM), fluorescence spectra, and zeta potential. CT imaging was recorded using micro‐CT scanning. Fluorescence imaging was measured using confocal laser scanning microscopy and flow cytometry. Results: The prepared AuNCs and MSNs possessed good properties as previously reported. The fluorescence intensity and CT value of the AuNCs were enhanced after being enriched with MSNs. The nanoparticles were both non‐cytotoxic. Confocal laser scanning microscopy and flow cytometry indicated that MSN@AuNCs in CAL‐27 cells showed improved fluorescence imaging compared with simple AuNCs at the same concentration. Conclusions: The results revealed that the strategy of enriching AuNCs with MSNs can obtain highly sensitive fluorescence/CT dual‐modal imaging, which indicated the potential of this nanoparticle in the diagnosis and treatment of disease. [ABSTRACT FROM AUTHOR]

Stimuli-responsive nanomedicines represent a pivotal technology for in situ on-demand drug release and offer multiple advantages over conventional drug delivery systems to combat rheumatoid arthritis(RA). However, the lack of sensitivity to a single-stimuli source or the inability to synchronize multi-stimuli responses can easily lead to challenges in achieving precise-theranostics of RA. Herein, a homology-activated ultrasensitive nanomedicines MnO 2 -CQ4T-GOx(MCG NMs) is designed for NIR-II fluorescence(NIR-II FL)/magnetic resonance imaging(MRI)-guided effective "knock-on" dynamic anti-RA therapy. Building upon the characteristics of the RA-microenvironment, the MCG innovatively construct a MnO 2 -Mn 2+ system, which can normalized activation sites. The ultrasensitive-responsive degradation is achieved using the multi-stimuli processes in the RA-microenvironment, triggering release of functional small molecules. The produced Mn 2+ can exert Fenton-like activity to generate •OH from H 2 O 2 , thus providing the effective chemodynamic therapy(CDT). Moreover, the up-regulation of H 2 O 2 by GOx-catalysis not only sensitizes the MnO 2 -Mn 2+ system but also achieves self-enhancing CDT efficacy. The NIR-II FL quenching of CQ4T-BSA in the aggregated state occurs in MCG NMs, which can be rapidly and precisely "turn-on" via the MnO 2 -Mn 2+ system. Meanwhile, the integration of activated Mn 2+ -based MRI imaging has successfully developed an activatable dual-modal imaging. Feedback imaging-guided precise photodynamic therapy of CQ4T-BSA can achieve efficient "knock-on" dynamic therapy for RA., (© 2024 Wiley‐VCH GmbH.)

Dynamic variations in the concentration and abnormal distribution of endogenous biomarkers are strongly associated with multiple physiological and pathological states. Therefore, it is crucial to design imaging systems capable of real-time detection of dynamic changes in biomarkers for the accurate diagnosis and effective treatment of diseases. Recently, ratiometric imaging has emerged as a widely used technique for sensing and imaging of biomarkers due to its advantage of circumventing the limitations inherent to conventional intensity-dependent signal readout methods while also providing built-in self-calibration for signal correction. Here, the recent progress of ratiometric probes and their applications in sensing and imaging of biomarkers are outlined. Ratiometric probes are classified according to their imaging mechanisms, and ratiometric photoacoustic imaging, ratiometric optical imaging including photoluminescence imaging and self-luminescence imaging, ratiometric magnetic resonance imaging, and dual-modal ratiometric imaging are discussed. The applications of ratiometric probes in the sensing and imaging of biomarkers such as pH, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), gas molecules, enzymes, metal ions, and hypoxia are discussed in detail. Additionally, this Review presents an overview of challenges faced in this field along with future research directions.

Abstract Cell‐derived microparticles, which are recognized as nanosized phospholipid bilayer membrane vesicles, have exhibited great potential to serve as drug delivery systems in cancer therapy. However, for the purpose of comprehensive therapy, microparticles decorated with multiple therapeutic components are needed, but effective engineering strategies are limited and still remain enormous challenges. Herein, Bi2Se3 nanodots and doxorubicin hydrochloride (DOX) co‐embedded tumor cell‐derived microparticles (Bi2Se3/DOX@MPs) are successfully constructed through ultraviolet light irradiation‐induced budding of parent cells which are preloaded with Bi2Se3 nanodots and DOX via electroporation. The multifunctional microparticles are obtained with high controllability and drug‐loading capacity without unfavorable membrane surface destruction, maintaining their excellent intrinsic biological behaviors. Through membrane fusion cellular internalization, Bi2Se3/DOX@MPs show enhanced cellular internalization and deepened tumor penetration, resulting in extreme cell damage in vitro without considering endosomal escape. Because of their distinguished photothermal performance and tumor homing target capability, Bi2Se3/DOX@MPs exhibit admirable dual‐modal imaging capacity and outstanding tumor suppression effect. Under 808 nm laser irradiation, intravenous injection of Bi2Se3/DOX@MPs into H22 tumor‐bearing mice results in remarkably synergistic antitumor efficacy by combining photothermal therapy with low‐dose chemotherapy in vivo. Furthermore, the negligible hemolytic activity, considerable metabolizability, and low systemic toxicity of Bi2Se3/DOX@MPs imply their distinguished biocompatibility and great potential for tumor theranostics.