The targeting ability, drug‐loading capacity, and size of the drug nanocarriers are crucial for enhancing the therapeutic index for cancer therapy. Herein, the morphology and size‐controllable fabrication of supramolecular tumor‐targeting nanocarriers based on host–guest recognition between a novel pillar[5]arene‐based prodrug WP5‐DOX and a Arg‐Gly‐Asp (RGD)‐modified sulfonate guest RGD‐SG is reported. The amphiphilic WP5‐DOX⊃RGD‐SG complex with a molar ratio of 5:1 self‐assembles into vesicles, whereas smaller‐sized micelles can be obtained by changing the molar ratio to 1:3. This represents a novel strategy of controllable construction of supramolecular nanovehicles with different sizes and morphologies based on the same host−guest interactions by using different host−guest ratios. Furthermore, in vitro and in vivo studies reveal that both these prodrug nanocarriers could selectively deliver doxorubicin to RGD receptor‐overexpressing cancer cells, leading to longer blood retention time, enhanced antitumor efficacy, and reduced systematic toxicity in murine tumor model, suggesting their potential application for targeted drug delivery.

Branched and dendrimeric cationic peptides have shown better transfection efficiency than linear peptides, owing to their superior capacity for inducing DNA condensation. We have designed and synthesized two analogously guanidinocarbonylpyrrole‐substituted (GCP‐substituted) branched cationic tripeptides that provide extremely strong electrostatic attraction towards DNA. Both ligands 1 and 2 can bind to DNA and form condensed complexes, owing to the branched structure and high positive charges, as demonstrated by isothermal titration calorimetry (ITC), ζ potential and atomic force microscopy (AFM). After the replacement of the carboxylate group by an amide group, binding of ligand 2 to DNA shows exothermic enthalpy and positive entropy changes relative to ligand 1. Rational interpretation would suggest that ligand 2 might aid the translocation of plasmid pF143 to HEK 293T cells, showing high gene transfection efficiency. This work therefore provides a facile way, by modifying a branched cationic tripeptide with GCP, to turn a peptide even a tripeptide into an efficient gene transfection vector.

Small peptides capable of assembling into well-defined nanostructures have attracted extensive attention due to their interesting applications as biomaterials. This work reports the first example of a pillararene functionalized with a guanidiniocarbonyl pyrrole (GCP)-conjugated short peptide segment. The obtained amphiphilic peptide 1 spontaneously self-assembles into a supramolecular β-sheet in aqueous solution based on host-guest interaction between pillararene and GCP unit as well as hydrogen-bonding between the peptide strands. Interestingly, peptide 1 at low concentration shows transitions from small particles to "pearl necklace" assemblies, and finally to branched fibers in a time-dependent process. At higher concentration, it directly assembles into twisted β-sheet tapes. Notably, without pillararene moiety, the control peptide A forms α-helix structure with morphology changing from particles to bamboo-like assemblies depending on concentration, indicating a significant role of the pillararene-GCP host-guest interaction for the secondary structure formation. Moreover, peptide 1 can serve as an efficient gene transfection vector.

Development of fluorescence markers for the 14-3-3 adapter protein class.

Herein, we report a rather simple strategy to enhance the anion binding ability of a dipeptide to achieve cell uptake and also protein delivery. Peptide 1, composed of only two synthetic amino acids with an artificial anion binding site in the side chains, has an overall molecular weight of only 630 Da and demonstrated strong binding affinity (107 M-1) and clustering ability with heparin as a model for cell surface sugars. Furthermore, peptide 1 is also efficiently taken up by cells most likely via endocytosis. The uptake efficiency is dependent on the amount of glycosaminoglycans on the cell surface. Cells with reduced amounts of surface bound glycosaminoglycans show significantly less uptake of peptide 1. Moreover, 1 induced the uptake of a model protein (avidin, around 67 kDa) into cells, which makes 1 a highly attractive candidate for drug and protein delivery, especially as 1 has negligible cytotoxicity.