Peptide-based targeting strategies for simultaneous imaging and therapy with nanovectors

Over recent years, multifunctional compounds that combine diagnostic and therapeutic modalities using one unified material have been developed and designated as theranostics. These compounds provide the chance to develop individually designed therapies against various diseases to accomplish personalized medicine. In this review, theranostic agents based on nanovectors (liposomes, naposomes, micelles, polymeric micelles and micelles built around a solid core) externally modified with targeting peptides able to simultaneously carry a drug and a contrast agent are described, demonstrating that peptide-modified nanovectors can selectively carry a drug to target cells with an imaging probe co-incorporated into the nanovector to monitor therapy

Liposomes derivatized with tetrabranched Neurotensin peptide via click chemistry reactions

Liposomes decorated with Neurotensin tetramers are obtained by using a post-liposomal derivatization method in which a click-chemistry reaction between liposomes containing azido functions on the external surface and branched neurotensin peptides modified for the presence of a C-C triple-bond is performed

Fmoc-Diphenylalanine Hydrogels: Optimization of Preparation Methods and Structural Insights

Hydrogels (HGs) are tri-dimensional materials with a non-Newtonian flow behaviour formed by networks able to encapsulate high amounts of water or other biological fluids. They can be prepared using both synthetic or natural polymers and their mechanical and functional properties may change according to the preparation method, the solvent, the pH, and to others experimental parameters. Recently, many short and ultra-short peptides have been investigated as building blocks for the formulation of biocompatible hydrogels suitable for different biomedical applications. Due to its simplicity and capability to gel in physiological conditions, Fmoc-FF dipeptide is one of the most studied peptide hydrogelators. Although its identification dates to 15 ago, its behaviour is currently studied because of the observation that the final material obtained is deeply dependent on the preparation method. To collect information about their formulation, here are reported some different strategies adopted until now for the Fmoc-FF HG preparation, noting the changes in the structural arrangement and behaviour in terms of stiffness, matrix porosity, and stability induced by the different formulation strategy on the final materia

Nanostructures by Self-assembling Peptide Amphiphile as Potential Selective Drug Carriers

The self-assembling behaviour, at physiological pH, of the amphiphile peptide (C18)(2)L5CCK8 in nanostructures is reported. Stable aggregates presenting a critical micellar concentration of 2 X 10(-6) mol kg(-1), and characterized by water exposed CCK8 peptide in P-sheet conformation, are obtained. Small angle neutron scattering experiments are indicative for a 3D structure with dimensions >= 100 nm. AFM images confirm the presence of nanostructures. Fluorescence experiments indicating the sequestration of pyrene, chosen as drug model, and the anticancer Doxorubicin within the nanostructures are reported

Naposomes: a new class of peptide-derivatized, target-selectivemultimodal nanoparticles for imaging and therapeutic applications

Modified supramolecular aggregates for selective delivery of contrast agents and/or drugs are examined with a focus on a new class of peptide-derivatized nanoparticles: naposomes. These nanoparticles are based on the co‑aggregation of two different amphiphilic monomers that give aggregates of different shapes and sizes (micelles, vesicles and liposomes) with diameters ranging between 10 and 300 nm. Structural properties and in vitro and in vivo behaviors are discussed. For the high relaxitivity values (12–19 mM-1s-1) and to detect for the presence of a surface exposed peptide, the new peptide-derived supramolecular aggregates are very promising candidates as targetselective MRI contrast agents. The efficiency of surface-exposed peptides in homing these nanovectors to a specific target introduces promising new opportunities for the development of diagnostic and therapeutic agents with high specificity toward the biological target and reduced toxic side effects on nontarget organs

Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs.

Active targeting by means of drug encapsulated nanoparticles decorated with targeting bioactive moieties represents the next frontier in drug delivery; it reduces drug side effects and increases the therapeutic index. Peptides, based on their chemical and biological properties, could have a prevalent role to direct drug encapsulated nanoparticles, such as liposomes, micelles, or hard nanoparticles, toward the tumor tissues. A considerable number of molecular targets for peptides are either exclusively expressed or overexpressed on both cancer vasculature and cancer cells. They can be classified into three wide categories: integrins; growth factor receptors (GFRs); and G-protein coupled receptors (GPCRs). Therapeutic agents based on nanovectors decorated with peptides targeting membrane receptors belonging to the GPCR family overexpressed by cancer cells are reviewed in this article. The most studied targeting membrane receptors are considered: somatostatin receptors; cholecystokinin receptors; receptors associated with the Bombesin like peptides family; luteinizing hormone-releasing hormone receptors; and neurotensin receptors. Nanovectors of different sizes and shapes (micelles, liposomes, or hard nanoparticles) loaded with doxorubicin or other cytotoxic drugs and externally functionalized with natural or synthetic peptides are able to target the overexpressed receptors and are described based on their formulation and in vitro and in vivo behaviors

Amphiphilic CCK peptides assembled in supramolecular aggregates: structural investigations and in vitro studies

Supramolecular aggregates obtained by self-aggregation of five new cationic amphiphilic CCK8 peptides have been obtained in water solution and characterized for: (i) aggregate structure and stability; (ii) CCK8 peptide conformation and bioavailability on the external aggregate surface; and (iii) for their cell binding properties. The cationic amphiphilic CCK8 peptides self-aggregate giving a combination of liposomal and micelle structures, with radii ranging between B60 nm and B90 nm, and between B5 and B10 nm, respectively. The presence of CCK8 peptide well-exposed on the aggregate surface is demonstrated by fluorescence measurements. Peptide conformation changes in the five supramolecular aggregates: the CCK8 conformational behaviour is probably induced by the presence of three charged lysine residues close to the bioactive peptide sequence. Only aggregates in which the CCK8 peptide presents a structural arrangement similar to that found for the same peptide in DPC micelles give promising binding properties to CCK2-R receptors overexpressed by transfected A431 cells. Chemical modifications on the CCK8 N-terminus seem to play an important role in stabilizing the peptide active conformation, either when the peptide derivative is in monomeric or in aggregate form. For their easy preparation procedures and their binding properties, supramolecular aggregates based on cationic peptide amphiphiles can be considered as promising candidates for target selective drug carriers on cancer cells

Supramolecular aggregates containing lipophilic Gd(III) complexes as contrast agents in MRI

Magnetic resonance imaging (MRI) contrast agents based on paramagnetic gadolinium complexes are widely used in biomedical research and diagnosis. Their application is intended to improve efficacy of MRI providing physiological information along with the impressive anatomical detail already obtained by images without contrast. The classical gadolinium complexes currently used for MRI contrast enhancement are all lowmolecularweightcompounds that rapidly equilibrate between the intra and extravascular spaces after intravenous administration. In order to obtain gadolinium-based agents with different pharmacokinetic properties, supramolecular aggregates such as micelles and liposomes have been recently proposed. Micelles and liposomes, obtained by the aggregation of lipophilic gadolinium complexes are here described, with the aim to correlate their structural and relaxometric properties.We report on the state of the art in the development of supramolecular aggregates obtained by self-assembly of lipophilic gadolinium complexes and aggregates in which lipophilic gadolinium complexes are assembled with surfactants. Moreover aggregates derivatized with bioactive molecules, such as peptides and antibodies, acting as target selective MRI contrast agents are described

Micelles by self-assembling peptide-conjugate amphiphile: synthesis and structural characterization.

The solid-phase synthesis of a novel amphiphilic peptide conjugate I, contg. in the same mol. three different functions: N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-L-glutamic acid chelating agent, the CCK8 bioactive peptide, and a hydrophobic moiety contg. four alkyl chains with 18 carbon atoms each, is reported. In water soln. at pH 7.4, I self-assembles in very stable micelles at very low concn. [crit. micellar concn. (cmc) values of 5 10-7 mol kg-1] as confirmed by fluorescence spectroscopy. The structural characterization, obtained with small-angle neutron scattering (SANS) measurements, indicates that the aggregates are substantially represented by ellipsoidal micelles with an aggregation no. of 39 2 and the two micellar axes of about 52 and 26