Targeting of vascular intervention by systemically delivered supramolecular nanofibers after balloon angioplasty is described. Tracking of self-assembling peptide amphiphiles using fluorescence shows selective binding to the site of vascular intervention. Cylindrical nanostructures are observed to target the site of arterial injury, while spherical nanostructures with an equivalent diameter display no binding.

We successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases.

Author ContributionsThe manuscript was written through contributions of all authors. NDT, LCP, MRK1 (Karver), and MDS designed TF-targeted peptide sequences. MKK performed all conventional TEM. MKK conceived and designed the rat experiments and performed the surgeries. HAK assisted with the rat hemorrhage model. MKK and RHL conceived and designed the mouse experiments, with laser injury performed by RHL. DCG and BRD provided assistance with tissue processing and handling. MKK conceived, designed, and performed the TEG experiments. DCG provided additional assistance with TEGs. MDS and TDC performed CD spectroscopy. TDC performed cryo-TEM, SAXS, and WAXS. MRK1 synthesized all PAs. WB, EBP, LCP, NDT, TAP, SIS, MRK2 (Kibbe) helped guide the research. MKK, NDT, MRK2 interpreted all results. EBP assisted with statistical analysis. EBP and JRR performed CAC measurements. MKK prepared the initial draft of the manuscript. NDT and MRK2 critically revised the manuscript. MRK2, SIS, and BG provided oversight and funding of the entire project. All authors have given approval to the final version of the manuscript. Supporting InformationA table of the three letter codes, amino acid sequences, and corresponding Factor VII residues for the peptides incorporated into PA molecules; crystal structure models of the putative interaction sites of the targeting peptides on TF; HPLC-MS traces showing purity of synthesized PAs; cryogenic TEM of 25% SFE and 75% SBC-2 PA nanofibers; WAXS analysis of backbone, 25% SFE, and 75% SBC-2 PA nanofibers; CD spectroscopy of FKD and TQD PA nanofibers; fluorescent quantification of tested ratios of SFE and SBC-2 PA nanofibers; the critical aggregation concentration determinations for the 75% SBC-2, 25% SFE, and backbone PAs; and real-time localization of 75% SBC-2 in a mouse laser injury model. This material is available free of charge via the internet at http:// pubs.acs.org.

Children in northern Nigeria and elsewhere in the hot, arid western Sahel, are at risk of having their lung function compromised by a variety of factors, including undernutrition, environmental factors (e.g. airborne pollutants such as dust and smoke from wood fires), chronic upper-respiratory tract infections, and low socioeconomic class. We were interested in using spirometry to compare the pulmonary function of Nigerian children and adolescents aged 6-18 years who were living in urban and rural settings with the corresponding standards for African-American children. A total of 183 boys and girls in the rural village of Sabon Fobur on the Jos Plateau and another 128 boys and girls in the city of Jos were tested to determine their forced vital capacity (FVC), FVC at 1 s (FVC1), and peak expiratory flow (PEF). The nutritional status of the subjects was determined by measuring the body mass index (BMI), triceps skin-fold thickness, and mid-arm circumference, and fat-free mass (FFM) and fat mass (FM) by bioelectrical impedance analysis. According to the results of anthropometry, the subjects in Sabon Fobur and Jos were lean but generally adequately nourished. The mean FVC, FVC1 and PEF values for the rural males were 1.851,1.761, and 3.521, and for the urban males they were 1.971,1.791, and 3.471, respectively. The corresponding values for the rural females were 1.791,1.701, and 3.371, and for the urban females they were 1.761,1.671, and 3.091. These values were approximately 100 per cent of the corresponding values for African-American children. In general, strong correlations were found between each of the three lung function parameters and age, weight, height (only for the males), BMI, MAC, and FFM. These results show that: (1) the lung function of Nigerian children and adolescents living in either rural or urban areas were similar and compared favorably with African-American standards, and (2) weight was as important as height in determining pulmonary function. The inclusion of FFM as an explanatory variable did notfurther increase the accuracy of the prediction, even in a population where malnutrition may be prevalent. Therefore, we conclude that measurements of height and weight are all that are required for the assessment of lung function using spirometry in Nigerian children.

Hospitalizations, which affect quality of life, differ little between elderly and younger patients on HD. Therefore, hospitalizations do not constitute an argument for restricting access to HD to elderly patients.