Project description:The conjugation of taurine with a dipeptide derivative affords a cell compatible, small molecular hydrogelator to form hydrogels that exhibit rich phase transition behaviors in response to sonication and the change of pH or temperature.
Project description:Immune checkpoint blockers (ICBs) have shown great promise at harnessing immune system to combat cancer. However, only a fraction of patients can directly benefit from the anti-programmed cell death protein 1 (aPD1) therapy, and the treatment often leads to immune-related adverse effects. In this context, we developed a prodrug hydrogelator for local delivery of ICBs to boost the host's immune system against tumor. We found that this carrier-free therapeutic system can serve as a reservoir for extended tumoral release of camptothecin and aPD1 antibody, resulting in an immune-stimulating tumor microenvironment for boosted PD-1 blockade immune response. Our in vivo results revealed that this combination chemoimmunotherapy elicits robust and durable systemic anticancer immunity, inducing tumor regression and inhibiting tumor recurrence and metastasis. This work sheds important light into the use of small-molecule prodrugs as both chemotherapeutic and carrier to awaken and enhance antitumor immune system for improved ICBs therapy.
Project description:Simultaneous control of the kinetics and thermodynamics of two different types of covalent chemistry allows pathway selectivity in the formation of hydrogelating molecules from a complex reaction network. This can lead to a range of hydrogel materials with vastly different properties, starting from a set of simple starting compounds and reaction conditions. Chemical reaction between a trialdehyde and the tuberculosis drug isoniazid can form one, two, or three hydrazone connectivity products, meaning kinetic gelation pathways can be addressed. Simultaneously, thermodynamics control the formation of either a keto or an enol tautomer of the products, again resulting in vastly different materials. Overall, this shows that careful navigation of a reaction landscape using both kinetic and thermodynamic selectivity can be used to control material selection from a complex reaction network.
Project description:Herein, we report the rational design of a DEVD-based heptapeptide hydrogelator 1 which is susceptible to caspase-3 (CASP3), and its isomeric control hydrogelator 2 with a DEDV-based heptapeptide sequence. Self-assembly of 1 in water results in flexuous, long nanofibers to form supramolecular hydrogel I with higher mechanical strength than that of hydrogel II which is composed of rigid, short nanofibers of 2. In vitro enzymatic analysis indicated that 1 is susceptive to CASP3 while 2 is not. 3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyl tetrazolium bromide (MTT) and Western blot analyses indicated that DEDV-based hydrogelator 2 induces cell death via apoptotic pathway while the DEVD-based hydrogelator 1 minimizes cellular apoptosis induction.
Project description:The potential of surface-enhanced Raman scattering (SERS) spectroscopy in both laboratory and field analyses depends on the reliable formation of so-called SERS hot spots, such as those formed during gold or silver nanoparticle aggregation. Unfortunately such aggregates are not stable in solution because they typically grow until they precipitate. Here we describe the use of low-molecular-weight hydrogels formed through pH-triggered self-assembly that occurs at a rate that well matches the rates of aggregation of Au or Ag colloids, allowing them to be trapped at the SERS-active point in the aggregation process. We show that the colloid-containing gels give SERS signals similar to the parent colloid but are stable over several months. Moreover, lyophilized gels can be stored as dry powders for subsequent use in the analyses of gases and dissolved analytes by contact with either solutions or vapors. The present system shows how the combination of pH-switchable low-molecular-weight gelators and pH-induced colloid aggregation can be combined to make a highly stable, low-cost SERS platform for the detection of volatile organic compounds and the microvolume analysis of solutions.
Project description:We present herein the development of a new polycationic cyclophane: the "red box", second in a series of hydrazone-based analogues of the well-known organic receptor cyclobis(paraquat-p-phenylene)cyclophane ("blue box"). The macrocycle has been prepared in an excellent yield in aqueous media, and shows both a remarkable pH-responsiveness and unusual hydrolytic stability of the two hydrazone C[double bond, length as m-dash]N bonds, associated with charge delocalization of the amine lone pair. Whilst in aqueous media the "red box" is able to complex a variety of aromatic substrates, both in its acidic and basic form, in organic media the cyclophane is only able to capture those in the acidic form, resulting in supramolecular pH-responsiveness.
Project description:Supramolecular hydrogels are composed of self-assembled solid networks that restrict the flow of water. l-Phenylalanine is the smallest molecule reported to date to form gel networks in water, and it is of particular interest due to its crystalline gel state. Single and multi-component hydrogels of l-phenylalanine are used herein as model materials to develop an NMR-based analytical approach to gain insight into the mechanisms of supramolecular gelation. Structure and composition of the gel fibres were probed using PXRD, solid-state NMR experiments and microscopic techniques. Solution-state NMR studies probed the properties of free gelator molecules in an equilibrium with bound molecules. The dynamics of exchange at the gel/solution interfaces was investigated further using high-resolution magic angle spinning (HR-MAS) and saturation transfer difference (STD) NMR experiments. This approach allowed the identification of which additive molecules contributed in modifying the material properties.
Project description:The interaction between homochiral substituted perylene bisimide (PBI) molecule and the D enantiomer of phenylalanine amino acid was monitored. Spectroscopic transitions of PBI derivative in aqueous solution in the visible range were used to evaluate the presence of D-phenylalanine. UV-visible, fluorescence, FT-IR, and AFM characterizations showed that D-phenylalanine induces significant variations in the chiral perylene derivative aggregation state and the mechanism is enantioselective as a consequence of the 3D analyte structure. The interaction mechanism was further investigated in presence of interfering amino acid (D-serine and D-histidine) confirming that both chemical structure and its 3D structure play a crucial role for the amino acid discrimination. A D-phenylalanine fluorescence sensor based on perylene was proposed. A limit of detection (LOD) of 64.2 ± 0.38 nM was calculated in the range 10-7-10-5 M and of 1.53 ± 0.89 μM was obtained in the range 10-5 and 10-3 M.
Project description:This report describes the two component self-assembly of π-capped amino acid hydrogelators (serine (S), aspartic acid (D), glutamic acid (E) or lysine (K)) prepared from pyrene (Py) based donor and naphthalenediimide (NDI) based acceptor molecules. The co-assembly can be triggered to form hydrogels by varying the pH conditions and the major driving forces behind the hydrogelation were found to be the formation of a strong charge-transfer (CT) complex and hydrogen bonding interactions at suitable pH conditions. The NDI-Py blends with matched donor/acceptor amino acid pairs undergo self-assembly under acidic pH conditions, whereas the blend (NDI-S + Py-K) with a mismatched amino acid pair forms a stable hydrogel under physiological pH conditions. UV-Vis, FTIR and rheological studies clearly indicate the formation and the stability of these CT-induced hydrogels. These hydrogels are of nanofibrous morphology with an average diameter of about 6-9 nm as evidenced by TEM analysis. In addition, this novel NDI-Py mixed component system exhibited good biocompatibility towards PC3 cells. Overall, since hydrogels based on CT-mediated two-component assemblies are very rare, our newly discovered NDI-Py hydrogels provide chemical insights into the design of a CT-induced hydrogelator and might facilitate various applications in biomedical engineering.
Project description:Supramolecular packing dictates the physical properties of bio-inspired molecular assemblies in the solid state. Yet, modulating the stacking modes of bio-inspired supramolecular assemblies remains a challenge and the structure-property relationship is still not fully understood, which hampers the rational design of molecular structures to fabricate materials with desired properties. Herein, we present a co-assembly strategy to modulate the supramolecular packing of N-terminally capped alanine-based assemblies (Ac-Ala) by changing the amino acid chirality and mixing with a nonchiral bipyridine derivative (BPA). The co-assembly induced distinct solid-state stacking modes determined by X-ray crystallography, resulting in significantly enhanced electromechanical properties of the assembly architectures. The highest rigidity was observed after the co-assembly of racemic Ac-Ala with a bipyridine coformer (BPA/Ac-DL-Ala), which exhibited a measured Young's modulus of 38.8 GPa. Notably, BPA crystallizes in a centrosymmetric space group, a condition that is broken when co-crystallized with Ac-L-Ala and Ac-D-Ala to induce a piezoelectric response. Enantiopure co-assemblies of BPA/Ac-D-Ala and BPA/Ac-L-Ala showed density functional theory-predicted piezoelectric responses that are remarkably higher than the other assemblies due to the increased polarization of their supramolecular packing. This is the first report of a centrosymmetric-crystallizing coformer which increases the single-crystal piezoelectric response of an electrically active bio-inspired molecular assembly. The design rules that emerge from this investigation of chemically complex co-assemblies can facilitate the molecular design of high-performance functional materials comprised of bio-inspired building blocks.