Background-Recent studies have shown that stem cell therapy can promote tissue regeneration; however, monitoring stem cells in vivo remains problematic owing to limitations of conventional histological assays and imaging modalities. Methods and Results-Murine embryonic stem (ES) cells were stably transduced with a lentiviral vector carrying a novel triple-fusion (TF) reporter gene that consists of firefly luciferase, monomeric red fluorescence protein, and truncated thymidine kinase (fluc-mrfp-ttk). ES cell viability, proliferation, and differentiation ability were not adversely affected by either reporter genes or reporter probes compared with nontransduced control cells (PϭNS). Afterward, 1ϫ10 7 of ES cells carrying the TF reporter gene (ES-TF) were injected into the myocardium of adult nude rats (nϭ20). Control animals received nontransduced ES cells (nϭ6). At day 4, the bioluminescence and positron emission tomography signals in study animals were 3.7ϫ10 7 Ϯ5.8ϫ10 6 photons · s Ϫ1 · cm Ϫ2 per steradian (sr) and 0.08Ϯ0.03% injected dose/g, respectively (PϽ0.05 versus control). Both signals increased progressively from week 1 to week 4, which indicated ES cell survival and proliferation in the host. Histological analysis demonstrated the formation of intracardiac and extracardiac teratomas. Finally, animals (nϭ4) that were treated with intraperitoneal injection of ganciclovir (50 mg/kg) did not develop teratomas when compared with control animals (nϭ4) treated with saline (1 mL/kg). Conclusion-This is the first study to characterize ES cells that stably express fluorescence, bioluminescence, and positron emission tomography reporter genes and monitor the kinetics of ES cell survival, proliferation, and migration. This versatile imaging platform should have broad applications for basic research and clinical studies on stem cell therapy.

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A novel method of rare-earth cation-assisted ligand assembly has been developed to provide upconversion nanophosphors with T(1)-enhanced magnetic resonance (MR), radioactivity, and targeted recognition properties, making these nanoparticles potential candidates for multimodal bioimaging. The process of modifying the surface of the nanophosphors has been confirmed by transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, proton nuclear magnetic resonance, Fourier-transform infrared spectroscopy, energy-dispersive X-ray analysis, and so on. The versatility of this surface modification approach for incorporating functional molecules and fabricating fluorine-18-labeled magnetic-upconversion nanophosphors as multimodal bioprobes has been demonstrated by targeted cell imaging, in vivo upconversion luminescence, MR imaging, and positron emission tomography imaging of whole-body small animals.

Micro/nanorobots have been extensively explored as a tetherless small-scale robotic biodevice to perform minimally invasive interventions in hard-to-reach regions. Despite the emergence of versatile micro/nanorobots in recent years, matched in vivo development remains challenging, limited by unsatisfactory integration of core functions. Herein, we report a polydopamine (PDA)-coated magnetic microswimmer consisting of a magnetized Spirulina (MSP) matrix and PDA surface. Apart from the properties of the existing MSP (e.g., robust propulsion, natural fluorescence, tailored biodegradation, and selective cytotoxicity), the introduced PDA coating enhances the photoacoustic (PA) signal and photothermal effect of the MSP, thus making PA image tracking and photothermal therapy possible. Meanwhile, the PDA’s innate fluorescence quenching and diverse surface reactivity allows an off–on fluorescence diagnosis with fluorescence probes (e.g., coumarin 7). As a proof of concept, real-time image tracking (by PA imaging) and desired theranostic capabilities of PDA-MSP microswimmer swarms are demonstrated for the treatment of pathogenic bacterial infection. Our study suggests a feasible antibacterial microrobot for in vivo development and a facile yet versatile functionalization strategy of micro/nanorobots.

Selective receptor-targeting peptide based agents have attracted considerable attention in molecular imaging of tumor cells that overexpress corresponding peptide receptors due to their unique properties such as rapid clearance from circulation as well as high affinities and specificities for their targets. The rapid growth of chemistry modification techniques has enabled the design and development of various peptide-based imaging agents with enhanced metabolic stability, favorable pharmacokinetics, improved binding affinity and selectivity, better imaging ability as well as biosafety. Among them, many radiolabeled peptides have already been translated into the clinic with impressive diagnostic accuracy and sensitivity. This review summarizes the current status in the development of peptide-based imaging agents with an emphasis on the consideration of probe design including the identification of suitable peptides, the chemical modification of probes and the criteria for clinical translation. Specific examples in clinical trials have been provided as well with respect to their diagnostic capability compared with other FDA approved imaging agents.

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Without coordinated strategies to mitigate the immunosuppressive nature of the tumor microenvironment, cancer immunotherapy generally offers limited clinical benefit for established tumors. Tumor-associated macrophages (TAMs) are the critical driver of this immunosuppressive tumor microenvironment, which also promotes tumor metastasis. Here we successfully reprogrammed TAMs to an antitumor M1 phenotype using precision nanoparticle-based reactive oxygen species photogeneration, which demonstrated superior efficiency and efficacy over lipopolysaccharide stimulation. Meanwhile, antigen presentation and T-cell-priming by TAMs were enhanced by inhibiting lysosomal proton pump and proteolytic activity or by promoting tumor associated antigen release in the cytoplasm. The reprogrammed TAMs orchestrate cytotoxic lymphocyte (CTL) recruitment in the tumor and direct memory T-cells toward tumoricidal responses. This strategy could effectively eradicate tumors, inhibit metastasis, and further prevent their recurrence, which holds tremendous promise to realize potent cancer immunotherapy.

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