Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvβ3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8+ T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.
It was hypothesized that the catalyst nanoceria can increase inflammation/oxidative stress from the basal and reduce it from the elevated state. Macrophages clear nanoceria. To test the hypothesis, M0 (non-polarized), M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated, regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Inflammatory responses were quantified by IL-1β level, arginase activity, and RT-qPCR and metabolic changes and oxidative stress by the mito and glycolysis stress tests (MST and GST). Morphology was determined by light microscopy, macrophage phenotype marker expression, and a novel three-dimensional immunohistochemical method. Nanoceria blocked IL-1β and arginase effects, increased M0 cell OCR and GST toward the M2 phenotype and altered multiple M1- and M2-like cell endpoints toward the M0 level. M1-like cells had greater volume and less circularity/roundness. M2-like cells had greater volume than M0 macrophages. The results are overall consistent with the hypothesis.
Light microscopy has been a favorite tool of biological studies for almost a century, recently producing detailed images with exquisite molecular specificity achieving spatial resolution at nanoscale. However, light microscopy is insufficient to provide chemical information as a standalone technique. An increasing amount of evidence demonstrates that optical photothermal infrared microspectroscopy (O-PTIR) is a valuable imaging tool that can extract chemical information to locate molecular structures at submicron resolution. To further investigate the applicability of sub-micron infrared microspectroscopy for biomedical applications, we analyzed the contribution of substrate chemistry to the infrared spectra acquired from individual neurons grown on various imaging substrates. To provide an example of correlative immunofluorescence/O-PTIR imaging, we used immunofluorescence to locate specific organelles for O-PTIR measurement, thus capturing molecular structures at the sub-cellular level directly in cells, which is not possible using traditional infrared microspectroscopy or immunofluorescence microscopy alone.
The near-infrared fluorescence imaging has been integrated into the operating room to guide tumor resection, potentially reducing the positive margin rates in breast-conserving surgery (BCS). Relative to the widely used first near-infrared fluorescence imaging, imaging in the second near-infrared (NIR-II) region possesses higher contrast and deeper tissue penetration, particularly in the NIR-IIb window, offering many new opportunities for imaging-guided BCS. Here, we fabricated the c(RGDfC) functionalized erbium-based rare-earth nanoparticles (ErNPs@cRGD) with superior optical property in NIR-IIb region. Owing to deeper tissue penetration and efficient tumor targeting, ErNPs@cRGD-based NIR-IIb fluorescence imaging achieved enhanced signal-to-background ratios in tumor visualization, which was able to guide more complete tumor resection, identify multiple microtumors and distinguish malignant lesions from normal tissues in various mice models. Based on these, this NIR-IIb imaging strategy for surgical navigation can significantly reduce positive margin rates and improve prognosis, laying a foundation for the clinical resection of breast cancer.
The aim of the study was to investigate in vivo whether the application of immobilized superoxide dismutase (SOD) and catalase (CAT) could enhance DNA repairing systems and reduce level of CPD (cyclobutane pyrimidine dimers) and 6-4PP ((6-4) pyrimidine-pyrimidone photoproducts), and whether the immobilization on gold (AuNPs) and silver (AgNPs) nanoparticles affects the outcome. The study presents secondary analysis of our previous research. Three-day application of SOD and CAT in all forms of solution decreased the levels of CPD and 6-4PP boosted by UV irradiation. The mRNA expression level of the nucleotide excision repair (NER) system genes (XPA, XPC, ERCC1, ERCC2, ERCC3, LIG1) increased after application of immobilized and free enzymes. Increased by UV irradiation, p53 mRNA expression level normalized with the enzyme application. In conclusion, application of free and immobilized antioxidant enzymes accelerates removal of harmful effects of UV radiation in the rat skin by increasing expression level of NER genes.
Atherosclerosis remains the main cause of death and disability, as well as a leading cause of coronary arterial disease. Inflammation is one of the pathogenic factors of arteriosclerosis; however, the current treatments based on lowering the level of inflammation in the plaque tissue of patients with atherosclerosis are not clinically used. Herein, we hypothesize that αvβ3 receptor affinity and low pH sensitivity may be regarded as a valid therapeutic strategy for targeting sites of atherosclerosis according to the microenvironments of inflammation. To prove this tentative hypothesis, an acid-labile material polyketal named PK3 was synthesized, and the cRGDfc peptide was used to modify nanoparticles composed of poly(lactide-co-glycolide) (PLGA), lecithin, and PK3, loaded with the anti-atherosclerotic drug rapamycin (RAP). The nanoparticles were prepared using an O/W method and then characterized, which showed an appropriate particle size and fulfilling responsive behaviors. In vitro release studies and stability tests showed that these nanoparticles can be effectively internalized by human umbilical vein endothelial cells (HUVEC), and also show a good in vitro anti-inflammatory effect. After intravenous (i.v.) injection, RGD targeted by pH-responsive nanotherapy (RAP-Nps-RGD) may be accumulated at the plaque site in ApoE−/− mice with atherosclerosis and can effectively attenuate plaque progression compared to other formulations. Moreover, its good safety profile and biocompatibility have been revealed in both in vitro and in vivo estimations. Accordingly, the prospect of nanoparticles responsive to the inflammatory microenvironment for preventing atherosclerotic through inflammation modulation provides great feasibility for the administration of alternate drug molecules to inflamed sites to slow down the process of arteriosclerosis.