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Abstract Lymph node metastasis is a major metastatic route of cancer and significantly influences the prognosis of cancer patients. Radical lymphadenectomy is crucial for a successful surgery. However, iatrogenic normal organ injury during lymphadenectomy is a troublesome complication. Here, this paper reports a kind of organic nanoprobes (IDSe‐IC2F nanoparticles (NPs)) with excellent second near‐infrared (NIR‐II) fluorescence and photothermal properties. IDSe‐IC2F NPs can effectively label lymph nodes and helped achieve high‐contrast lymphatic imaging. More importantly, by jointly using IDSe‐IC2F nanoparticles and other kinds of nanoparticles with different excitation/emission properties, a multichannel NIR‐II fluorescence imaging modality and imaging‐guided lymphadenectomy is proposed. With the help of this navigation system, the iatrogenic injury can be largely avoided. In addition, NIR‐II fluorescence imaging‐guided photothermal treatment (“hot” strategy) can ablate those metastatic lymph nodes which are difficult to deal with during resection (“cold” strategy). Nanoprobes‐assisted and multichannel NIR‐II fluorescence imaging‐guided “cold” and “hot” treatment strategy provides a general new basis for the future precision surgery.

Background: Ex vivo and in vivo detection and imaging of adenosine triphosphate (ATP) is critically important for the diagnosis and treatment of diseases, which still remains challenges up to present. Results: We herein demonstrate that ATP could be fluorescently detected and imaged ex vivo and in vivo. In particular, we fabricate a kind of fluorescent ATP probes, which are made of titanium carbide (TC) nanosheets modified with the ROX-tagged ATP-aptamer (TC/Apt). In the constructed TC/Apt, TC shows superior quenching efficiency against ROX (e.g., ~ 97%). While in the presence of ATP, ROX-tagged aptamer is released from TC surface, leading to the recovery of fluorescence of ROX under the 545-nm excitation. Consequently, a wide dynamic range from 1 μM to 1.5 mM ATP and a high sensitivity with a limit of detection (LOD) down to 0.2 μM ATP can be readily achieved by the prepared TC/Apt. We further demonstrate that the as-prepared TC/Apt probe is feasible for accurate discrimination of ATP in different samples including living cells, body fluids (e.g., mouse serum, mouse urine and human serum) and mouse tumor models. Conclusions: Fluorescence detection and imaging of ATP could be readily achieved in living cells, body fluids (e.g., urine and serum), as well as mouse tumor model through a new kind of fluorescent ATP nanoprobes, offering new powerful tools for the treatment of diseases related to abnormal fluctuation of ATP concentration. [ABSTRACT FROM AUTHOR]

Lymph node metastasis is a major metastatic route of cancer and significantly influences the prognosis of cancer patients. Radical lymphadenectomy is crucial for a successful surgery. However, iatrogenic normal organ injury during lymphadenectomy is a troublesome complication. Here, this paper reports a kind of organic nanoprobes (IDSe‐IC2F nanoparticles (NPs)) with excellent second near‐infrared (NIR‐II) fluorescence and photothermal properties. IDSe‐IC2F NPs can effectively label lymph nodes and helped achieve high‐contrast lymphatic imaging. More importantly, by jointly using IDSe‐IC2F nanoparticles and other kinds of nanoparticles with different excitation/emission properties, a multichannel NIR‐II fluorescence imaging modality and imaging‐guided lymphadenectomy is proposed. With the help of this navigation system, the iatrogenic injury can be largely avoided. In addition, NIR‐II fluorescence imaging‐guided photothermal treatment ("hot" strategy) can ablate those metastatic lymph nodes which are difficult to deal with during resection ("cold" strategy). Nanoprobes‐assisted and multichannel NIR‐II fluorescence imaging‐guided "cold" and "hot" treatment strategy provides a general new basis for the future precision surgery. [ABSTRACT FROM AUTHOR]

During the past two decades, there is an explosive growth of numerous scientific researches on dual-emitting fluorescence ratiometric nanoprobes (FRNPs). FRNPs adopt dual-signal ratiometry as signal output toward specific targets, and exhibit unique in-built signal self-calibration function and high accuracy for target detection. Especially, FRNPs can perform high-performance detection of in-vitro/in-vivo pH. These explored FRNPs-pH systems were extensively applied to pH-sensing, imaging and therapeutic applications at the levels of living cells and small animals. Thereby, this review has systematically summarized the promising FRNPs-pH systems reported in recent years. The first section has clearly introduced dual-emission fluorescence (FL) ratiometric modes and FL sensing mechanisms during the construction and application processes. The second section wholly summarizes various construction methods of FRNPs-pH systems based on different compositions and structures. The third section rationally discusses potential applications of FRNPs-pH systems, referring to FL bioimaging at the levels of living cells and small animals, pH-sensing and imaging detection at the levels of whole cells, organelles, tissues and organs, as well as FL imaging-guided tumor therapy. Furthermore, the current status, potential challenges and development perspectives in following researches are analyzed reasonably. This comprehensive and timely review promotes further explorations of multifunctional luminescent nanoprobes and versatile sensing materials for highly efficient biomedical applications. [Display omitted] • his review summarizes studies on dual-emitting fluorescence ratiometric nanoprobes (FRNPs-pH) of in-vitro/in-vivo pH. • Various types, construction methods, sensing, imaging and therapeutic applications of FRNPs-pH are summarized regularly. • This review rationally discusses current status, possible challenges and perspectives of FRNPs-pH in forthcoming studies. [ABSTRACT FROM AUTHOR]

• Progress of nanoprobes for MR imaging of brain diseases is summarized. • Strategies for MRI nanoprobes to overcome blood–brain barrier are discussed. • Applications of MRI nanoprobes in disease-diagnostic imaging are reviewed. • Challenges and perspectives of MRI nanoprobes for brain diseases are discussed. Increasing brain disease incidence has become a common cause of disability and death worldwide. Early diagnosis of brain diseases is crucial to improve the prognosis of patients and reduce the mortality rate. In this regard, magnetic resonance imaging (MRI) is now playing an essential role in the early diagnosis of brain diseases due to its high spatial resolution, outstanding performance of soft tissue imaging, high penetration depth, and noninvasiveness. Brain disease diagnosis by MRI has achieved significant progress, but distinguishing healthy tissues from diseased tissue needs to be substantially improved. The emergence and prosperous development of nanomaterials provides an efficient strategy for the construction of functional magnetic resonance nanoprobes. Based on the nanoprobes with high specificity, desirable sensitivity, prominent signal intensity, targeting, and controllable metabolism, we can achieve better imaging of brain diseases at the structural as well as functional level, which can further provide diagnostic and therapeutic values. In this comprehensive review, we summarized and discussed the current progress of engineering nanoprobes for MR imaging of brain diseases, ranging from the types of MRI probes, stimulus-responsive design, and BBB penetrating methods, to their versatile applications in several typical brain diseases. The unsettled challenges and future perspectives on the rational design of MRI nanoprobes and their further clinical translations have also been discussed and forecasted. [ABSTRACT FROM AUTHOR]

Abstract So far, the development of a unique strategy for specific biomolecules activity monitoring and precise drugs release in cancerous cells is still challenging. Here, we designed a conformation-switchable smart nanoprobe to monitor telomerase activity and to enable activity-triggered drug release in cancerous cells. The straightforward nanoprobe contained a gold nanoparticle (AuNP) core and a dense layer of 5-carboxyfluorescein (FAM)-labeled hairpin DNA shell. The 3′ region of hairpin DNA sequence could function as the telomerase primer to be elongated in the presence of telomerase, resulting in the conformational switch of hairpin DNA. As a result, the FAM fluorescence was activated and the anticancer drug doxorubicin (Dox) molecules which intercalated into the stem region of the hairpin DNA sequence were released into cancerous cells simultaneously. The smart method could specifically distinguish cancerous cells from normal cells based on telomerase activity. It also showed a good performance for monitoring telomerase activity in the cytoplasm by molecular imaging and precise release of Dox triggered by telomerase activity in cancerous cells. These advantages may offer a great potential of this method for monitoring telomerase activity in cancer progression and estimating therapeutic effect.

First reported in 1994, stimulated emission depletion (STED) microscopy has long been regarded as a powerful tool for real-time superresolved bioimaging . However, high STED light power (101∼3 MW/cm2) is often required to achieve significant resolution improvement, which inevitably introduces phototoxicity and severe photobleaching, damaging the imaging quality, especially for long-term cases. Recently, the employment of nanoprobes (quantum dots, upconversion nanoparticles, carbon dots, polymer dots, AIE dots, etc.) in STED imaging has brought opportunities to overcoming such long-existing issues. These nanomaterials designed for STED imaging show not only lower STED power requirements but also more efficient photoluminescence (PL) and enhanced photostability than organic molecular probes. Herein, we review the recent progress in the development of nanoprobes for STED imaging, to highlight their potential in improving the long-term imaging quality of STED microscopy and broadening its application scope. We also discuss the pros and cons for specific classes of nanoprobes for STED bioimaging in detail to provide practical references for biological researchers seeking suitable imaging kits, promoting the development of relative research field.

Detection of glutathione (GSH) in the body is essential to accurately map the redox state of cells and real‐time visualization of physiological and pathological conditions in vivo. However, traditional fluorescence (FL) imaging in the near‐infrared I region (NIR‐I, 650–900 nm) is difficult to quantitively visualize GSH in vivo due to the tissue autofluorescence background and disastrous photon scattering. Herein, a NIR‐IIb (1500–1700 nm) nanoprobe consisting of 4‐nitrophenol‐Cy7 (NPh) conjugated lanthanide‐based downconversion nanoparticles (DCNP@NPh‐PEG) is developed for in vivo ratiometric imaging of GSH. In the presence of GSH, NPh shows responsively enhanced FL emission at 808 nm, thus enhancing FL signal at 1550 nm of DCNPs excited by 808 nm (F1550, 808Ex) through non‐radiative energy transfer (NRET) effect, while the fluorescence of DCNP at 1550 nm excited by 980 nm laser (F1550, 980Ex) is stable because no NRET occurred. The ratiometric F1550, 980Ex/F1550, 808Ex value exhibits a linearship with GSH concentration ranged from 0–24 mm with detection limit of 0.3 mm. The NIR‐IIb nanoprobe has excellent performance in detecting and imaging GSH in both subcutaneous tumor and orthotopic colon tumor in vivo with high accuracy and resolution. The design strategy of the ratiometric NIR‐II FL nanoprobe based on the activated FERT effect provides a reliable tool for the development of NIR‐II nanoprobes for accurate biosensing in vivo. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm–HSA–ICG–PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results: The size of the CCm–HSA–ICG–PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm–HSA–ICG–PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm–HSA–ICG–PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm–HSA–ICG–PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm–HSA–ICG–PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm–HSA–ICG–PFTBA till 14 days. Conclusions: By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm–HSA–ICG–PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients. [ABSTRACT FROM AUTHOR]

Near-infrared nanoconstructs present a potentially effective platform for site-specific and deep tissue optical imaging and phototherapy. We have engineered a polymeric nanocapsule composed of polyallylamine hydrochloride (PAH) chains cross-linked with sodium phosphate and doped with indocyanine green (ICG) toward such endeavors. The ICG-doped nanocapsules were coated covalently with polyethylene glycol (5000 daltons) through reductive amination. We administrated the constructs by tail vein injection to healthy mice. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, due to encapsulation, offers the potential of extending the clinical applications of ICG, which are currently limited due to rapid elimination of ICG from the vasculature. Our results also indicate that PAH and ICG-doped nanocapsules (ICG-NCs) are not cytotoxic at the levels used in this study.

Thrombosis is a frequent predisposing factor in high‐mortality cardiovascular diseases, which underscores the urgent need to precisely diagnose thrombosis formation at a less severe stage. However, it is still challenging to realize in vivo early thrombosis imaging due to lack of high sensitivity/‐specificity molecular imaging strategy. To address such problems, thrombin‐activatable scintillating nanoprobes are developed for background‐free X‐ray‐excited luminescence (XEL) imaging of in vivo early thrombosis. The nanoprobes are constructed by designing bright XEL‐emitting lanthanide‐doped scintillator nanocrystals (NCs) with dye labeled‐peptide modification. Such nanoprobes show XEL‐off originally and enable robust turn‐on XEL upon thrombin‐specific cleavage of the peptide, resulting from the rational manipulation of energy transfer between dye and NCs. Specially, due to high tissue penetration depth and background‐free attributes in XEL imaging, this strategy achieves high‐efficiency XEL imaging of the early thrombosis on the basis of in situ elevated thrombin levels. Moreover, XEL and magnetic resonance imaging capabilities can be integrated to further improve imaging accuracy and monitor thrombosis progression. As such, the exploited strategy demonstrates a novel paradigm for realizing timely thrombosis imaging and provides a new readily tailorable platform for sensitive in vivo deep‐tissue imaging. [ABSTRACT FROM AUTHOR]

A tumor microenvironment often presents altered physicochemical characteristics of the extracellular matrix (ECM) including changes in matrix composition, stiffness, protein expression, pH, temperature, or the presence of certain stromal and immune cells. Of these, overexpression of matrix metalloproteinases (MMPs) and extracellular acidosis are the two major hallmarks of cancer that can be exploited for tumor detection. The change in matrix stiffness and the release of certain cytokines (TNF-α) in the tumor microenvironment play major roles in inducing MMP-9 expression in cancerous cells. This study highlights the role of mechanical cues in upregulating MMP-9 expression in cancerous cells using stiffness-tunable matrix compositions and dual-sensitive fluorescent nanoprobes. Ionically cross-linked 3D alginate/gelatin (AG) scaffolds with three stiffnesses were chosen to reflect the ECM stiffnesses corresponding to healthy and pathological tissues. Moreover, a dual-sensitive nanoprobe, an MMP-sensitive peptide conjugated to carbon nanoparticles with intrinsic pH fluorescence properties, was utilized for in situ monitoring of the two cancer hallmarks in the 3D scaffolds. This platform was further utilized for designing a 3D core-shell platform for spatially mapping tumor margins and for visualizing TNF-α-induced MMP-9 expression in cancerous cells.

Alzheimer's disease is the most common cause of dementia and a leading cause of mortality in the elderly population. Diagnosis of Alzheimer's disease has traditionally relied on evaluation of clinical symptoms for cognitive impairment with a definitive diagnosis requiring post-mortem demonstration of neuropathology. However, advances in disease pathogenesis have revealed that patients exhibit Alzheimer's disease pathology several decades before the manifestation of clinical symptoms. Magnetic resonance imaging (MRI) plays an important role in the management of patients with Alzheimer's disease. The clinical availability of molecular MRI (mMRI) contrast agents can revolutionize the diagnosis of Alzheimer's disease. In this article, we review advances in nanoparticle contrast agents, also referred to as nanoprobes, for mMRI of Alzheimer's disease. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease., (© 2024 Wiley Periodicals LLC.)

Atherosclerosis (AS) is a crucial contributor to various cardiovascular diseases (CVDs), which seriously threaten human life and health. Early and accurate recognition of AS plaques is essential for the prevention and treatment of CVD. Herein, we introduce an AS-targeting nanoprobe based on near-infrared (NIR) persistent luminescence nanoparticles (PLNPs), developing a highly sensitive NIR persistent luminescence (PersL) AS plaque imaging technique and successfully realizing early AS plaque detection. The nanoprobe exhibits good monodispersity and regular spherical morphology and also owns exceptional NIR PersL performance upon repetitive irradiation by biological window light. The surface-conjugated antibody (anti-osteopontin) endowed nanoprobe excellent targeting ability to foam cells within plaques. After intravenously injected nanoprobe into AS model mice, the highly sensitive PersL imaging technique can accurately detect AS plaques prior to ultrasonography (US) and magnetic resonance imaging (MRI). Specifically, the NIR PersL imaging reveals AS plaques at the earliest within 2 weeks, with higher signal-to-background ratio (SBR) up to 5.72. Based on this technique, the nanoprobe has great potential for applications in the prevention and treatment of CVD, the study of AS pathogenesis, and the screening of anti-AS drugs.

Real-time, noninvasive, and nonradiative bone imaging can directly visualize bone health but requires bone-targeted probes with high specificity. Herein, we propose that carboxyl-rich fluorescent nanoprobes are easily absorbed by macrophages in bone marrow during circulation, enabling optical bone marrow imaging in vivo . We used PbS/CdS core-shell quantum dots with NIR-IIb (1500-1700 nm) emission as substrates to prepare the carboxyl-rich nanoprobe. In vivo NIR-IIb fluorescence imaging with the nanoprobes showed high resolution and penetration depth in bone tissues and allowed for imaging-guided fracture diagnosis. Bone tissue slices showed substantial accumulation of carboxyl nanoprobes in the bone marrow and strong colocalization with macrophages. Similar results with CdSe quantum dots and an organic nanofluorophore suggest that carboxyl surface modification is effective to achieve bone marrow targeting, providing a novel strategy for developing bone/bone marrow imaging probes.

Herein, an advanced bioconjugation technique to synthesize hybrid polymer-antibody nanoprobes tailored for fluorescent cell barcoding in flow cytometry-based immunophenotyping of leukocytes is applied. A novel approach of attachment combining two fluorescent dyes on the copolymer precursor and its conjugation to antibody is employed to synthesize barcoded nanoprobes of antibody polymer dyes allowing up to six nanoprobes to be resolved in two-dimensional cytometry analysis. The major advantage of these nanoprobes is the construct design in which the selected antibody is labeled with an advanced copolymer bearing two types of fluorophores in different molar ratios. The cells after antibody recognition and binding to the target antigen have a characteristic double fluorescence signal for each nanoprobe providing a unique position on the dot plot, thus allowing antibody-based barcoding of cellular samples in flow cytometry assays. This technique is valuable for cellular assays that require low intersample variability and is demonstrated by the live cell barcoding of clinical samples with B cell abnormalities. In total, the samples from six various donors were successfully barcoded using only two detection channels. This barcoding of clinical samples enables sample preparation and measurement in a single tube., (© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Tumor cell heterogeneity leads to differences in tumor proliferation and invasiveness, as well as drug sensitivity. These factors affect the diagnosis, treatment, and monitoring of tumor progression. Thus, analysis of tumor cell subpopulations is crucial for tumor diagnosis and individualized treatment. This study describes an approach to capture and sequentially isolate tumor cells subpopulations based on antibody‐mediated recognition and magnetic gradient separation, using biomimetic immuno‐fluorescent magnetic multifunctional nanoprobes, consisting of magnetic γ‐Fe2O3 and fluorescent quantum dots as the core, and leukocyte membrane vesicles with antibodies as the shell. Upon binding with leukocyte membrane‐coated fluorescent magnetic nanoparticles with antibodies (LFMNPs‐Ab), the model of three types of breast cancer cells with different expression levels of Her2 marker on the cell surface, namely, BT474Her2+++, MDA‐MB‐453Her2++, and MDA‐MB‐231Her2+, develop different magnetic susceptibilities. Based on the differences in their magnetic response under constant external magnetic field, the three tumor cell subpopulations in blood samples are magnetically separated and collected sequentially at 90, 120, and 180 s, respectively, as confirmed by a subsequent fluorescent imaging assay. The magnetic gradient separation‐based strategy described in the present study is a simple, fast, and feasible method for targeted separation of tumor cell subpopulations, and shows great potential for clinical study. [ABSTRACT FROM AUTHOR]

The in vivo spatio-temporal patterns of neovascularization are still poorly understood because it is limited to multi-scale techniques from the cellular level to living animal level. Owing to deep tissue-penetration and zero autofluorescence background, the second near-infrared (NIR-II, 1,000–1,700 nm) fluorescence imaging recently shows promise in breaking through this dilemma by dynamically tracking the pathophysiological process of neovascularization in vivo. Here, NIR-II fluorescence imaging was recruited for monitoring blood vessels in order to visualize the vascular injury and quantitively assess neovascularization in mouse models of acute skeleton muscle contusion and hindlimb ischemia. The temporal analysis of real-time NIR-II fluorescence intensity demonstrated that the blood flow perfusion of ischemia area was able to rapidly restore to 96% of pre-ischemic state within one week. Moreover, the spatial analysis revealed that the lower and outer quadrants of ischemia area in the mouse model of hindlimb ischemia always had relatively high blood flow perfusion compared with other quadrants during three weeks post-ischemia, and even exceeded pre-ischemic quantity at 21 days post-ischemia. In conclusion, this in vivo imaging technique has significant potential utility for studying the spatio-temporal patterns of neovascularization in vivo. [ABSTRACT FROM AUTHOR]

Abstract Hypoxia has been identified to contribute the pathogenesis of a wide range of liver diseases, and therefore, quantitative mapping of liver hypoxia is important for providing critical information in the diagnosis and treatment of hepatic diseases. However, the existing imaging methods are unsuitable to quantitatively assess liver hypoxia due to the need of liver‐specific contrast agents and be easily affected by other imaging factors. Here, a time‐resolved lifetime‐based imaging method is established for quantitative mapping of the distribution of hypoxia in the livers of mice by combining a wide‐field luminescence lifetime imaging system with an oxygen‐sensitive nanoprobe. It is shown that the method is suitable for real‐time quantification of the change of oxygen pressure in the process of hepatic ischemia‐reperfusion of the mouse. Moreover, the developed lifetime imaging methodology is used to quantitatively map liver hypoxia regions in the mouse model of orthotopic liver tumor, where the average oxygen pressure in tumorous liver is far below the normal liver.

Fluorescent nanoprobes containing ionophores and solvatochromic dyes (SDs) were previously reported as an alternative to chromoionophore-based nano-optodes. However, the small-molecular SDs are prone to leakage and sequestration in complex samples. Here, we chemically attached the SDs to the surface of organosilica nanospheres through copper-catalyzed Click chemistry to prevent dye leakage. The nano-optodes remained well responsive to K+ even after exposure to a large amount of cation-exchange resin, which acted as a sink of the SDs. The potassium nanoprobes exhibited a dynamic range between 1 μM to 10 mM and a good selectivity thanks to valinomycin. Preliminary sensing device based on a nylon filter paper and agarose hydrogel was demonstrated. The results indicate that the covalent anchoring of SDs on nanospheres is promising for developing ionophore-based nanoprobes.

Recently, multimodality molecular imaging has evolved into a fast-growing research field with goals of detecting and measuring biological processes in vivo non-invasively. Researchers have come to realize that the complementary abilities of different imaging modalities over single modality could provide more precisely information for the diagnosis of diseases. At present, nanoparticles-based multimodal imaging probes have received significant attention because of their ease of preparation and straightforward integration of each modality into one entity. More importantly, nanotechnology has an increasing impact on multimodality molecular imaging of cardiovascular diseases, such as atherosclerosis and vulnerable plaque, myocardial infarction, angiogenesis, apoptosis and so on. In this review, we briefly summarize that various nanoprobes are exploited for targeted molecular imaging of cardiovascular diseases, as well as associated multimodality imaging approaches and their applications in the diagnosis and treatment of cardiovascular diseases.

Abstract Background Pancreatic cancer remains the leading cause of cancer-related deaths, the existence of cancer stem cells and lack of highly efficient early detection may account for the poor survival rate. Gadolinium ion-doped upconversion nanoparticles (UCNPs) provide opportunities for combining fluorescent with magnetic resonance imaging, and they can improve the diagnostic efficacy of early pancreatic cancer. In addition, as one transmembrane glycoprotein overexpressed on the pancreatic cancer stem cells, CD326 may act as a promising target. In this study, we developed a facile strategy for developing anti-human CD326-grafted UCNPs-based micelles and performed the corresponding characterizations. After conducting in vitro and vivo toxicology experiments, we also examined the active targeting capability of the micelles upon dual-mode imaging in vivo. Results We found that the micelles owned superior imaging properties and long-time stability based on multiple characterizations. By performing in vitro and vivo toxicology assay, the micelles had good biocompatibility. We observed more cellular uptake of the micelles with the help of anti-human CD326 grafted onto the micelles. Furthermore, we successfully concluded that CD326-conjugated micelles endowed promising active targeting ability by conducting dual-mode imaging in human pancreatic cancer xenograft mouse model. Conclusions With good biocompatibility and excellent imaging properties of the micelles, our results uncover efficient active homing of those micelles after intravenous injection, and undoubtedly demonstrate the as-obtained micelles holds great potential for early pancreatic cancer diagnosis in the future and would pave the way for the following biomedical applications.