Superstructure based on β-CD self-assembly induced by a small guest molecule

The size, shape and surface chemistry of nanoparticles play an important role in cellular interaction. Thus, the main objective of the present study was the determination of the β-cyclodextrin (β-CD) self-assembly thermodynamic parameters and its structure, aiming to use these assemblies as a possible controlled drug release system. Light scattering measurements led us to obtain the β-CD's critical aggregation concentration (cac) values, and consequently the thermodynamic parameters of the β-CD spontaneous self-assembly in aqueous solution: Δ[subscript agg]G[superscript o] = −16.31 kJ mol[superscript −1], Δ[subscript agg]H[superscript o] = −26.48 kJ mol[superscript −1] and TΔ[subscript agg]S[superscript o] = −10.53 kJ mol[superscript −1] at 298.15 K. Size distribution of the self-assembled nanoparticles below and above cac was 1.5 nm and 60–120 nm, respectively. The number of β-CD molecules per cluster and the second virial coefficient were identified through Debye's plot and molecular dynamic simulations proposed the three-fold assembly for this system below cac. Ampicillin (AMP) was used as a drug model in order to investigate the key role of the guest molecule in the self-assembly process and the β-CD:AMP supramolecular system was studied in solution, aiming to determine the structure of the supramolecular aggregate. Results obtained in solution indicated that the β-CD's cac was not affected by adding AMP. Moreover, different complex stoichiometries were identified by nuclear magnetic resonance and isothermal titration calorimetry experiments.Brazil. National Institute in Science and Technology in Nanobiopharmaceutics (NanoBiofar) (CNPq/MCT/FAPEMIG)Conselho Nacional de Pesquisas (Brazil)National Institutes of Health (U.S.) (Grant 1-R01-DE016516-03)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Process 4597-08-7)Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (CEX APQ-00498/08

Haploinsufficiency of CYP8B1 associates with increased insulin sensitivity in humans

10.1172/JCI152961The Journal of clinical investigation13221e152961

Ergothioneine, an adaptive antioxidant for the protection of injured tissues? A hypothesis

10.1016/j.bbrc.2015.12.124BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS4702245-25

Microengineering in cardiovascular research: new developments and translational applications

Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease. In recent years, advances in technical fabrication and biological integration have provided new insights into biological phenomena, improved diagnostic measurements, and made major steps towards de novo tissue creation. Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics. With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community

Thermostable exoshells fold and stabilize recombinant proteins

The expression and stabilization of recombinant proteins is fundamental to basic and applied biology. Here we have engineered a thermostable protein nanoparticle (tES) to improve both expression and stabilization of recombinant proteins using this technology. tES provides steric accommodation and charge complementation to green fluorescent protein (GFPuv), horseradish peroxidase (HRPc), and Renilla luciferase (rLuc), improving the yields of functional in vitro folding by ~100-fold. Encapsulated enzymes retain the ability to metabolize small-molecule substrates, presumably via four 4.5-nm pores present in the tES shell. GFPuv exhibits no spectral shifts in fluorescence compared to a nonencapsulated control. Thermolabile proteins internalized by tES are resistant to thermal, organic, chaotropic, and proteolytic denaturation and can be released from the tES assembly with mild pH titration followed by proteolysis.NMRC (Natl Medical Research Council, S’pore)Published versio

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

Following recent successes with percutaneous coronary intervention (PCI) for treating coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying collagen IV-rich basal lamina, which promotes both intravascular thrombosis and smooth muscle proliferation. Previously, we reported the engineering of collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm lipid–polymeric NPs were surface functionalized with collagen IV-targeting peptides and loaded with paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a ≥3.5-fold improved maximum tolerated dose versus paclitaxel. In efficacy studies using a rat carotid injury model, paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower neointima-to-media (N/M) scores at 2 wk versus control groups of saline, paclitaxel, or nontargeted NPs. Compared with sham-injury groups, an ∼50% reduction in arterial stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD.National Cancer Institute (U.S.) (grant CA151884)National Institute for Biomedical Imaging and Bioengineering (U.S.) (grant EB003647)National Heart, Lung, and Blood Institute. Program of Excellence in Nanotechnology (contract HHSN268201000045C)David H. Koch Cancer Research Fund (Prostate Cancer Foundation Award in Nanotherapeutics

Sources of variability in quantifying circulating thymosin beta-4: literature review and recommendations

10.1080/14712598.2018.1448382EXPERT OPINION ON BIOLOGICAL THERAPY18sup1141-14

Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic

Mammalian cell membranes are often incompatible with chemical modifications typically used to increase circulation half-life. Using cellular nanoghosts as a model, we show that proline-alanine-serine (PAS) peptide sequences expressed on the membrane surface can extend the circulation time of a cell membrane derived nanotherapeutic. Membrane expression of a PAS 40 repeat sequence decreased protein binding and resulted in a 90% decrease in macrophage uptake when compared with non-PASylated controls (P ≤ 0.05). PASylation also extended circulation half-life (t1/2 = 37 h) compared with non-PASylated controls (t1/2 = 10.5 h) (P ≤ 0.005), resulting in ~7-fold higher in vivo serum concentrations at 24 h and 48 h (P ≤ 0.005). Genetically engineered membrane expression of PAS repeats may offer an alternative to PEGylation and provide extended circulation times for cellular membrane-derived nanotherapeutics.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)National Medical Research Council (NMRC)CLD acknowledges support from the National Medical Research Council, NMRC/CSAINV17nov-0008, XCJ thanks support by A*STAR Biomedical Research Council (IAF-PP grant), and Singapore Ministry of Education Tier-1 Academic Research Funds (RG 131/15)

Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic

10.1016/j.nano.2019.02.024NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE18169-17