Peptide amphiphiles are capable of self-assembly into a diverse array of nanostructures including ribbons, tubes, and vesicles. However, the ability to select the morphology of the resulting structure is not well developed. We examined the influence of systematic changes in the number and type of hydrophobic and hydrophilic amino acids on the self-assembly of amphiphilic peptides. Variations in the morphology of self-assembled peptides of the form X(6)K(n) (X = alanine, valine, or leucine; K = lysine; n = 1-5) are investigated using a combination of transmission electron microscopy and dynamic light scattering measurements. The secondary structures of the peptides are determined using circular dichroism. Self-assembly is controlled through a combination of interactions between the hydrophobic segments of the peptide molecules and repulsive forces between the charged segments. Increasing the hydrophobicity of the peptide by changing X to a more lipophilic amino acid or decreasing the number of hydrophilic amino acids transforms the self-assembled nanostructures from vesicles to tubes and ribbons. Changes in the hydrophobicity of the peptides are reflected in changes in the critical micelle concentration observed using pyrene probe fluorescence analysis. Self-assembled materials formed from cationic peptide amphiphiles of this type display promise as carriers for insoluble molecules or negatively charged nucleic acids in drug or gene delivery applications.

A responsive drug delivery system (DDS) for oxaliplatin (OX) has been designed with a view to overcoming several common drawbacks associated with this widely used anticancer agent, including fast degradation/deactivation in the blood stream, lack of tumor selectivity, and low bioavailability.

The discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O 2 as a green oxidant. The C-H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2′-deoxy-5-difluoromethyluridine (F 2 TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery.

Gene therapy as a strategy for disease treatment requires safe and efficient gene delivery systems that encapsulate nucleic acids and deliver them to effective sites in the cell.

Polyamines are essential for the growth of eukaryotic cells and can be dysregulated in tumors. Here we describe a strategy to deplete polyamines through host–guest encapsulation using a peptide-pillar[5]arene conjugate (P1P5A, P1 = RGDSK(N 3 )EEEE) as a supramolecular trap. The RGD in the peptide sequence allows the molecule to bind to integrin α v β 3 -overexpressing tumor cells. The negative charged glutamic acid residues enhance the inclusion affinities between the pillar[5]arene and cationic polyamines via electrostatic interactions and facilitate the solubility of the conjugate in aqueous media. The trap P1P5A efficiently encapsulates polyamines with association constants of 10 5 –10 6 M −1 . We show that P1P5A has a wide spectrum of antitumor activities, and induces apoptosis via affecting the polyamine biosynthetic pathway. Experiments in vivo show that P1P5A effectively inhibits the growth of breast adenocarcinoma xenografts in female nude mice. This work reveals an approach for suppressing tumor growth by using supramolecular macrocycles to trap polyamines in tumor cells.