Peptides or peptide conjugates capable of assembling into one-dimensional (1D) nanostructures have been extensively investigated over the past two decades due to their implications in human diseases and also their interesting applications as biomaterials. While many of these filamentous assemblies contain a β-sheet-forming sequence as the key design element, their eventual morphology could assume a variety of shapes, such as fibrils, ribbons, belts, or cylinders. Deciphering the key factors that govern the stacking fashion of individual β-sheets will help understand the polymorphism of peptide assemblies and greatly benefit the development of functional materials from customized molecular design. Herein, we report the decisive role of electrostatic interactions in the lamination and untwisting of 1D assemblies of short peptides. We designed and synthesized three short peptides containing only six amino acids (EFFFFE, KFFFFK, and EFFFFK) to elucidate the effective control of β-sheet stacking. Our results clearly suggest that electrostatic repulsions between terminal charges reduce the pitch of the twisting β-sheet tapes, thus leading to highly twisted, intertwined fibrils or twisted ribbons, whereas reducing this repulsion, either through molecular design of peptide with opposite terminal charges or through coassembly of two peptides carrying opposite charges, results in formation of infinite assemblies such as belt-like morphologies. We believe these observations provide important insight into the generic design of β-sheet assemblies.

We report here the self-assembly of a rationally designed paclitaxel drug amphiphile into well-defined supramolecular filaments that possess a fixed 41% paclitaxel loading. These filaments can exert effective cytotoxicity against a number of cell lines comparable to that of free paclitaxel.

Gadolinium (Gd)-based compounds and materials are the most commonly used magnetic resonance imaging (MRI) contrast agents in the clinic; however, safety concerns associated with their toxicities in the free ionic form have promoted the development of new generations of metal-free contrast agents. Here we report a supramolecular strategy to convert an FDA-approved anticancer drug, Pemetrexed (Pem), to a molecular hydrogelator with inherent chemical exchange saturation transfer (CEST) MRI signals. The rationally designed drug–peptide conjugate can spontaneously associate into filamentous assemblies under physiological conditions and consequently form theranostic supramolecular hydrogels for injectable delivery. We demonstrated that the local delivery and distribution of Pem–peptide nanofiber hydrogels can be directly assessed using CEST MRI in a mouse glioma model. Our work lays out the foundation for the development of drug-constructed theranostic supramolecular materials with an inherent CEST MRI signal that enables noninvasive monitoring of their in vivo distribution and drug release.

BackgroundIn 2012, the European Society of Intensive Care Medicine proposed a definition for acute gastrointestinal injury (AGI) based on current medical evidence and expert opinion. The aim of the present study was to evaluate the feasibility of using the current AGI grading system and to investigate the association between AGI severity grades with clinical outcome in critically ill patients.MethodsAdult patients at 14 general intensive care units (ICUs) with an expected ICU stay ≥24 h were prospectively studied. The AGI grade was assessed daily on the basis of gastrointestinal (GI) symptoms, intra-abdominal pressures, and feeding intolerance (FI) in the first week of admission to the ICU.ResultsAmong the 550 patients enrolled, 456 patients (82.9%) received mechanical ventilation, and 470 patients were identified for AGI. The distribution of the global AGI grade was 24.5% with grade I, 49.4% with grade II, 20.6% with grade III, and 5.5% with grade IV. AGI grading was positively correlated with 28- and 60-day mortality (P < 0.0001). Univariate Cox regression analysis showed that age, sepsis, diabetes mellitus, coronary artery disease, the use of vasoactive drugs, serum creatinine and lactate levels, mechanical ventilation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the global AGI grade were significantly (P ≤ 0.02) associated with 60-day mortality. In a multivariate analysis including these variables, diabetes mellitus (HR 1.43, 95% CI 1.03–1.87; P = 0.05), the use of vasoactive drugs (HR 1.56, 95% CI 1.12–2.11; P = 0.01), serum lactate (HR 1.15, 95% CI 1.06–1.24; P = 0.03), global AGI grade (HR 1.65, 95% CI 1.28–2.12; P = 0.008), and APACHE II score (HR 1.04, 95% CI 1.02–1.06; P < 0.001) were independently associated with 60-day mortality. In a subgroup analysis of 402 patients with 7-day survival, in addition to clinical predictors and the AGI grade on the first day of ICU stay, FI within the first week of ICU stay had an independent and incremental prognostic value for 60-day mortality (χ2 = 41.9 vs. 52.2, P = 0.007).ConclusionsThe AGI grading scheme is useful for identifying the severity of GI dysfunction and could be used as a predictor of impaired outcomes. In addition, these results support the hypothesis that persistent FI within the first week of ICU stay is an independent determinant for mortality.Trial registrationChinese Clinical Trial Registry identifier: ChiCTR-OCS-13003824. Registered on 29 September 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1780-4) contains supplementary material, which is available to authorized users.

One key design feature in the development of any local drug delivery system is the controlled release of therapeutic agents over a certain period of time. In this context, we report the characteristic feature of a supramolecular filament hydrogel system that enables a linear and sustainable drug release over the period of several months. Through covalent linkage with a short peptide sequence, we are able to convert an anticancer drug, paclitaxel (PTX), to a class of prodrug hydrogelators with varying critical gelation concentrations. These self-assembling PTX prodrugs associate into filamentous nanostructures in aqueous conditions and consequently percolate into a supramolecular filament network in the presence of appropriate counterions. The intriguing linear drug release profile is rooted in the supramolecular nature of the self-assembling filaments which maintain a constant monomer concentration at the gelation conditions. We found that molecular engineering of the prodrug design, such as varying the number of oppositely charged amino acids or through the incorporation of hydrophobic segments, allows for the fine-tuning of the PTX linear release rate. In cell studies, these PTX prodrugs can exert effective cytotoxicity against glioblastoma cell lines and also primary brain cancer cells derived from patients and show enhanced tumor penetration in a cancer spheroid model. We believe this drugbearing hydrogel platform offers an exciting opportunity for the local treatment of human diseases.