Atherosclerosis, a leading cause of heart disease, results from chronic vascular inflammation that is driven by diverse immune cell populations. Nanomaterials may function as powerful platforms for diagnostic imaging and controlled delivery of therapeutics to inflammatory cells in atherosclerosis, but efficacy is limited by nonspecific uptake by cells of the mononuclear phagocytes system (MPS). MPS cells located in the liver, spleen, blood, lymph nodes, and kidney remove from circulation the vast majority of intravenously administered nanomaterials regardless of surface functionalization or conjugation of targeting ligands. Here, we report that nanostructure morphology alone can be engineered for selective uptake by dendritic cells (DCs), which are critical mediators of atherosclerotic inflammation. Employing near-infrared fluorescence imaging and flow cytometry as a multimodal approach, we compared organ and cellular level biodistributions of micelles, vesicles (i.e., polymersomes), and filomicelles, all assembled from poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS) block copolymers with identical surface chemistries. While micelles and filomicelles were respectively found to associate with liver macrophages and blood-resident phagocytes, polymersomes were exceptionally efficient at targeting splenic DCs (up to 85% of plasmacytoid DCs) and demonstrated significantly lower uptake by other cells of the MPS. In a mouse model of atherosclerosis, polymersomes demonstrated superior specificity for DCs (p < 0.005) in atherosclerotic lesions. Furthermore, significant differences in polymersome cellular biodistributions were observed in atherosclerotic compared to naïve mice, including impaired targeting of phagocytes in lymph nodes. These results present avenues for immunotherapies in cardiovascular disease and demonstrate that nanostructure morphology can be tailored to enhance targeting specificity.

The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T-cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)-bpoly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti-inflammatory agent 1,25-dihydroxyvitamin D3-(aVD) and ApoB-100-derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P-D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly lowdose intravenous administration of DC-targeted, aVD-loaded polymersomes significantly inhibit atherosclerotic lesion development in high-fat-diet-fed ApoE −/− mice. The results validate the key role of DC immunomodulation during aVD-dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell-targeted nanotherapy in the treatment of CVD.

Encapsulation within poly(ethylene glycol)-b-poly(propylene sulfide) micelles reduces the toxicity of celastrol and enhances its anti-inflammatory effect during treatment of atherosclerosis.

Advances in materials science and engineering through bio-inspiration, at both the micro-and nanoscales, have flourished over recent years. By understanding principles used in nature to produce adhesives and other substances of interest, the field of bio-inspired engineering has emerged as an important area of innovation. In this review, we will focus on bio-adhesives based on three main mechanisms of generating attachment: dry, wet, and chemical adhesion. Dry adhesion, involving micro-to nanoscale filamentous structures, is used by many insects and reptiles to rapidly climb surfaces. Tree frogs and some insects make use of wet adhesion by leveraging capillary forces through the design of attaching structures that increases liquid drainage, and hence increases frictional contact. Finally, chemical adhesion is used by many plants and mollusks, which secrete adhesives composed of proteins, polysaccharides and carbohydrates to generate the strong forces necessary for adhesion. This paper reviews recent discoveries in animal and plant bio-adhesives, and details the mechanisms used in several representative biological systems. We extend the review to include the fundamental principles functioning in each form of adhesion at the micro-and nanoscales. This fast emerging research area has significant implications in the future design of bio-inspired adhesives, and offers further potential for a variety of applications.

A facile method to synthesize flower-like gold nanostructures showing multiple tips with dendritic structures is developed through a one-step reduction of HAuCl 4 with dopamine at room temperature. The gold nanoflowers clearly increase the surface enhanced Raman scattering (SERS) effect, demonstrate promising biocompatibility, and could be internalized by cancer cells, indicating their potential for biomedical applications.

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PEG-b-PPS bicontinuous nanospheres resist degradation and stably retain payloads within cells. When loaded with a photosensitizing agent, these nanospheres demonstrate off–on inducible photo-responsive release of cytotoxic agents into the cytosol of cells.

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