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

Structure–Activity Relationships in NHC–Silver Complexes as Antimicrobial Agents

: Silver has a long history of antimicrobial activity and received an increasing interest in last decades owing to the rise in antimicrobial resistance. The major drawback is the limited duration of its antimicrobial activity. The broad-spectrum silver containing antimicrobial agents are well represented by N-heterocyclic carbenes (NHCs) silver complexes. Due to their stability, this class of complexes can release the active Ag+ cations in prolonged time. Moreover, the properties of NHC can be tuned introducing alkyl moieties on N-heterocycle to provide a range of versatile structures with different stability and lipophilicity. This review presents designed Ag complexes and their biological activity against Gram-positive, Gram-negative bacteria and fungal strains. In particular, the structure-activity relationships underlining the major requirements to increase the capability to induce microorganism death are highlighted here. Moreover, some examples of encapsulation of silver-NHC complexes in polymer-based supramolecular aggregates are reported. The targeted delivery of silver complexes to the infected sites will be the most promising goal for the future

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

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

Interaction of Cisplatin with a CCHC Zinc Finger Motif

The interaction between cisplatin and an 18-residue CCHC zinc finger motif derived from a retroviral nucleocapsid protein (PyrZf18) has been studied using UV–visible, CD and 1H NMR spectroscopies and ESI-MS spectrometry. Cisplatin irreversibly blocks the cysteine zinc binding groups in the free peptide and is able to slowly eject zinc from the zinc–peptide complex. The observed end product of the reaction with cisplatin is a complex in which only one ammonia molecule is coordinated to platinum. After an initial binding with two cysteine residues and the formation of the (PyrZf18)– platinum–(NH3)2 complex, a release of one ammonia molecule occurs because of trans-labilization, and the third cysteine is coordinated, leading to a mixture of isomers and/or conformers of the (PyrZf18)–platinum–NH3 complex. The results are discussed with respect to the potential antiretroviral activity of platinum(II) compounds and to the possible interaction of cisplatin with the cellular nucleic acid binding proteins

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

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