Macrophages are vital regulators of the host defense in organisms. In response to different local microenvironments, resting macrophages (M0) can be polarized into different phenotypes, pro-inflammatory (M1) or anti-inflammatory (M2), and perform different roles in different physiological or pathological conditions. Polarized macrophages can also be further reprogrammed by reversing their phenotype according to the changed milieu. Macrophage polarization and reprogramming play essential roles in maintaining the steady state of the immune system and are involved in the processes of many diseases. As foreign substances, nanoparticles (NPs) mainly target macrophages after entering the body. NPs can perturb the polarization and reprogramming of macrophages, affect their immunological function and, therefore, affect the pathological process of disease. Optimally-designed NPs for the modulation of macrophage polarization and reprogramming might provide new solutions for treating diseases. Systematically investigating how NPs affect macrophage polarization is crucial for understanding the regulatory effects of NPs on immune cells in vivo. In this review, macrophage polarization by NPs is summarized and discussed.

Among approaches of current cancer immunotherapy, a dendritic cell (DC)-targeted vaccine based on nanotechnology could be a promising way to efficiently induce potent immune responses. To enhance DC targeting and vaccine efficiency, we included imiquimod (IMQ), a toll-like receptor 7/8 (TLR 7/8) agonist, and monophosphoryl lipid A (MPLA), a TLR4 agonist, to synthesize lipid-polymer hybrid nanoparticles using PCL−PEG-PCL and DOTAP (IMNPs) as well as DSPE-PEG-mannose (MAN-IMNPS). The spatiotemporal delivery of MPLA (within the outer lipid layer) to extracellular TLR4 and IMQ (in the hydrophobic core of NPs) to intracellular TLR7/8 can activate DCs synergistically to improve vaccine efficacy. Ovalbumin (OVA) as a model antigen was readily absorbed by positively charged DOTAP and showed a quick release in vitro. Our results demonstrated that this novel nanovaccine enhanced cellular uptake, cytokine production, and maturation of DCs. Compared with the quick metabolism of free OVA-agonists, the depot effect of OVA-IMNPs was observed, whereas MAN-OVA-IMNPs promoted trafficking to secondary lymphoid organs. After immunization with a subcutaneous injection, the nanovaccine, especially MAN-OVA-IMNPs, induced more antigen-specific CD8 + T cells, greater lymphocyte activation, stronger cross-presentation, and more generation of memory T cells, antibody, IFN-γ, and granzyme B. Prophylactic vaccination of MAN-OVA-IMNPs significantly delayed tumor development and prolonged the survival in mice. The therapeutic tumor challenge indicated that MAN-OVA-IMNPs prohibited tumor progression more efficiently than other formulations, and the combination with an immune checkpoint blockade further enhanced antitumor effects. Hence, the DC-targeted vaccine codelivery with IMQ and MPLA adjuvants by hybrid cationic nanoparticles in a spatiotemporal manner is a promising multifunctional antigen delivery system in cancer immunotherapy.

The introduction of GW approximation to the electron's self‐energy by Hedin in the 1960s, where G and W denote the one‐particle Green's function and the screened Coulomb interaction, respectively, facilitates the computation of quasiparticle energies through Dyson's equation. GW method can also help us determine the electron–hole interaction, which is a functional derivative of self‐energy with respect to one‐particle Green's function, with excellent accuracy, and its combination with Bethe–Salpeter equation, which is derived from two‐particle Green's function, is a powerful tool to study electronic excitations and optical absorption. Thanks to the development of methodology and softwares during the last 30 years, the capability of GW method and Bethe–Salpeter equation to deal with real systems is elevated substantially, while they also exhibit many advantages over other first‐principles methods in band structures, ionization potentials, electron affinities, optical spectra, and so on. They have been successfully applied in the excited states of various systems, including crystals, metals, nanomaterials, chemical and biological systems, and so on. WIREs Comput Mol Sci 2016, 6:532–550. doi: 10.1002/wcms.1265 This article is categorized under: Electronic Structure Theory > Ab Initio Electronic Structure Methods Theoretical and Physical Chemistry > Spectroscopy

Long-term clinical studies of drug-eluting stents (DES) have reported high incidence of late thrombosis. Given the growing concern over the clinical application of this technology, we have developed a stent coated with bi-layered PLGA nanoparticles (BL-PLGA NPs) containing VEGF plasmid in the outer layer and paclitaxel (PTX) in the inner core (VEGF/PTX NPs). We hypothesized that early release of VEGF gene would promote re-endothelialization, while slow release of PTX would suppress smooth muscle cell proliferation. Using Fc plasmid as a reporter gene, we observed that Fc/PTX NPs successfully expressed Fc protein, but did not show cytotoxicity or anti-proliferative effect during the first 7 days in cell culture. In contrast, PTX NPs showed strong anti-proliferative effect staring from day 1 in culture, suggesting sequential release of gene and PTX from the BL-PLGA NPs. In vivo effects of the treated stent were assessed in mini-swines. Implantation of GFP/PTX NP-coated stents revealed efficient local GFP gene transfection at day 7. VEGF/PTX NP-coated stents showed complete re-endothelialization and significantly suppressed in-stent restenosis after 1 month compared to commercial DES. In conclusion, the VEGF/PTX NP-coated stents promote early endothelium healing while inhibit smooth muscle cell proliferation through sequential release of the VEGF gene and paclitaxel.

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