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Clarke Ebsen posted an update 6 months, 3 weeks ago
Macrophages have been associated with drug response and resistance in diverse settings, thus raising the possibility of using macrophage imaging as a companion diagnostic to inform personalized patient treatment strategies. Nanoparticle-based contrast agents are especially promising because they efficiently deliver fluorescent, magnetic, and/or radionuclide labels by leveraging the intrinsic capacity of macrophages to accumulate nanomaterials in their role as professional phagocytes. find more Unfortunately, current clinical imaging modalities are limited in their ability to quantify broad molecular programs that may explain (a) which particular cell subsets a given imaging agent is actually labeling, and (b) what mechanistic role those cells play in promoting drug response or resistance. Highly multiplexed single-cell approaches including single-cell RNA sequencing (scRNAseq) have emerged as resources to help answer these questions. In this review, we query recently published scRNAseq datasets to support companion macrophage imaging, with particular focus on using dextran-based nanoparticles to predict the action of anti-cancer nanotherapies and monoclonal antibodies.With the rapid development of anti-cancer cell-based therapies, such as adoptive T cell therapies using tumor-infiltrating T cells, T cell receptor transduced T cells, and chimeric antigen receptor T cells, there has been a growing interest in imaging technologies to non-invasively track transferred cells in vivo. Cell tracking using ex vivo cell labeling with positron emitting radioisotopes for positron emission tomography (PET) imaging has potential advantages over single-photon emitting radioisotopes. These advantages include intrinsically higher resolution, higher sensitivity, and higher signal-to-background ratios. Here, we review the current status of recently developed Zirconium-89 (89Zr)-oxine ex vivo cell labeling with PET imaging focusing on its applications and future perspectives. Labeling of cells with 89Zr-oxine is completed in a series of relatively simple steps, and its low radioactivity doses required for imaging does not interfere with the proliferation or function of the labeled immune cells. Preclinical studies have revealed that 89Zr-oxine PET allows high-resolution in vivo tracking of labeled cells for 1-2 weeks after cell transfer both in mice and non-human primates. These results provide a strong rationale for the clinical translation of 89Zr-oxine PET-based imaging of cell-based therapy.Rationale Stem Cells (SCs) show a great potential in therapeutics for restoring and regenerating native tissues. The clinical translation of SCs therapies is currently hindered by the inability to expand SCs in vitro in large therapeutic dosages, while maintaining their safety and potency. The use of biomaterials allows for the generation of active biophysical signals for directing SCs fate through 3D micro-scaffolds, such as the one named “Nichoid”, fabricated with two-photon laser polymerization with a spatial resolution of 100 nm. The aims of this study were i) to investigate the proliferation, differentiation and stemness properties of neural precursor cells (NPCs) following their cultivation inside the Nichoid micro-scaffold; ii) to assess the therapeutic effect and safety in vivo of NPCs cultivated in the Nichoid in a preclinical experimental model of Parkinson’s Disease (PD). Methods Nichoids were fabricated by two photon laser polymerization onto circular glass coverslips using a home-made SZ2080 photth Nichoid-grown NPCs, and this is accompanied by the recovery of dopaminergic markers expression in the striatum of PD affected mice. Conclusion SCs demonstrated an increase in pluripotency potential when expanded inside the Nichoid, without the need of any genetic modification of cells, showing great promise for large-scale production of safe and functional cell therapies to be used in multiple clinical applications.From the past decade, extracellular vesicles (EVs) have attracted considerable attention as tools for the selective delivery of anti-neoplastic drugs to cancer tissues. Compared to other nanoparticles, EVs display interesting unique features including immune compatibility, low toxicity and the ability to encapsulate a large variety of small- and macro-molecules. However, in virtually all studies, investigations on EVs have been focused on fully transformed cancers the possibility to apply EV technology also to early-stage tumors has never been explored. Methods Herein, we studied the ability of cancer-derived EVs to recognize and deliver their cargo also to incipient cancers. To this purpose, EV biodistribution was studied in MMTV-NeuT genetically modified mice during early mammary transformation, in fully developed breast tumors and in the normal gland of wild type syngeneic mice. EVs were loaded with indocyanine green (ICG), a near-infrared (NIR) dye together with oncolytic viruses and i.v. injected in mice. The nanoparticle biodistribution was assayed by in vivo and ex vivo optical imaging (detecting the ICG) and semiquantitative real-time PCR (measuring the adenoviral genome) in different tissues. Results Our results demonstrate the ability of cancer-derived EVs to recognize early-stage neoplastic tissues opening the possibility to selectively deliver theranostics also for tumor prevention. Conclusions Taken together our study demonstrates the ability of EVs to recognize and deliver diagnostic and therapeutic agents not only to fully transformed tissues but also to early stage tumors. These findings pave the way for the synthesis of “universal” EVs-based formulation for targeted cancer therapy.Background Bacterial co-infections are frequently identified in viral respiratory infections and are significant reasons for morbidity and mortality. Information on the prevalence of bacterial co-infection in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is lacking. The purpose of this study was to determine the prevalence of bacterial infections and antibiotic resistance in patients with coronavirus disease (COVID-19). Methods In a cross-sectional study, blood culture (BC) and endotracheal aspirate (ETA) were obtained from COVID-19 patients (RT-PCR positive for SARS-CoV-2). The bacterial isolates were confirmed by the standard microbiological methods. Antibiotic resistance was determined using the disk diffusion method. Results Among these 340 patients with COVID-19, a total of 43 (12.46%) patients had secondary bacterial infections. The most common bacteria isolated through ETA and BC included Klebsiella species 11 (25.59%), methicillin-sensitive Staphylococcus aureus (MSSA) 9 (20.
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