Current Topics in Medicinal Chemistry - Volume 15, Issue 13, 2015

The combined efforts of chemistry, nanotechnology, and spectroscopy led to the development of self-assembled fluorescent DNA nanostructures, an inexhaustible source of refined and bizarre tools and powerful techniques for research and diagnostic applications. This multidisciplinary area has tremendous prospects for science and technology.

The present article focuses on the amphiphilic cationic polymers as antibacterial agents. These polymers undergo self-assembly in aqueous conditions and impart biological activity by efficiently interacting with the bacterial cell wall, hence, used in preparing chemical disinfectants and biocides. Both cationic charge as well as hydrophobic segments facilitate interactions with the bacterial cell surface and initiate its disruption. The perturbation in transmembrane potential causes leakage of cytosolic contents followed by cell death. Out of two categories of macromolecules, peptide oligomers and cationic polymers, which have extensively been used as antibacterials, we have elaborated on the current advances made in the area of cationic polymer-based (naturally occurring and commonly employed synthetic polymers and their modified analogs) antibacterial agents. The development of polymer-based antibacterials has helped in addressing challenges posed by the drug-resistant bacterial infections. These polymers provide a new platform to combat such infections in the most efficient manner. This review presents concise discussion on the amphiphilic cationic polymers and their modified analogs having low hemolytic activity and excellent antibacterial activity against array of fungi, bacteria and other microorganisms.

This review reports the recent advances in chlorotoxin (CTX)-targeted nanoparticles (NPs) for imaging and therapy of glioma. CTX has been identified as a targeting ligand to specifically bind to glioma. Through different conjugation approaches, CTX can be conjugated onto iron oxide NPs, quantum dots, and rare-earth upconversion NPs for targeted magnetic resonance and fluorescence imaging of glioma. Likewise, CTX-conjugated NPs can also be used as a carrier system to load anticancer drugs or therapeutic genes for targeted chemotherapy or gene therapy of glioma, respectively. Some of the key developments in this area of research will be introduced in detail. Challenges and future perspectives in the development of CTX-conjugated NPs will be discussed.

The development of three-dimensional matrices capable of recapitulating the main features of native extracellular matrix and contribute for the establishment of a favorable microenvironment for cell behavior and fate is expected to circumvent some of the main limitations of cell-based therapies. In this context, self-assembly has emerged as a promising strategy to engineer cell-compatible hydrogels. A wide number of synthetically-derived biopolymers, such as proteins, peptides and DNA/RNA, with intrinsic ability to self-assemble into well-defined nanofibrous structures, are being explored. The resulting hydrogels, in addition to closely resembling the architecture of native cellular microenvironments, present a versatile and dynamic behavior that allows them to be designed to undergo sol-to-gel transition in response to exogenous stimulus. This review presents an overview on the state-of-the-art of the different strategies being explored for the development of injectable synthetic self-assembled hydrogels for cell transplantation and/or recruitment of endogenous cells, with an emphasis on their biological performance, both in vitro and in vivo. Systems based on peptides are the most widely explored and have already generated promising results in pre-clinical in vivo studies involving different repair/regenerative scenarios, including cartilage, bone, nerve and heart. On the other hand, systems based on DNA and hybrid hydrogels are now emerging for application in the biomedical field with high potential. Finally, the main challenges hampering the translation of these systems to the clinic and the issues that need to be addressed for these to progress from bench-to-bedside are discussed.

Self-assembled peptides and specifically small peptide based nanostructures have been the focus of research in past decade due to their potential biological applications. In this study, we prepared a protected peptide, Boc-Pro-Phe-Gly-OMe, which self-assembled in aqueous solutions leading to the formation of nanostructures and ability to act as a drug carrier. Dynamic light scattering (DLS) measurements showed nanostructures with average size of 119.6 nm containing hydrophobic core, wherein hydrophobic drugs, viz, eosin, aspirin and curcumin, were successfully encapsulated. These encapsulated nanostructures, were further stabilized with Vitamin E–TPGS. In-vitro drug release studies revealed the release of drugs in controlled fashion from the nanostructures. The results advocate the potential of the proposed peptide nanostructures as controlled drug delivery systems and could be used in other biomedical applications.

The concept of Nanomedicine emerged along with the new millennium, and it is expected to provide solutions to some of modern medicine’s unsolved problems. Nanomedicine offers new hopes in several critical areas such as cancer treatment, viral and bacterial infections, medical imaging, tissue regeneration, and theranostics. To explore all these applications, a wide variety of nanomaterials have been developed which include liposomes, dendrimers, nanohydrogels and polymeric, metallic and inorganic nanoparticles. Recently, interlocked systems, namely rotaxanes and catenanes, have been incorporated into some of these chemical platforms in an attempt to improve their performance. This review focus on the nanomedicine applications of nanomaterials containing interlocked structures. The introduction gives an overview on the significance of interdisciplinary science in the progress of the nanomedicine field, and it explains the evolution of interlocked molecules until their application in nanomedicine. The following sections are organized by the type of interlocked structure, and it comprises details of the in vitro and/or in vivo experiments involving each material: rotaxanes as imaging agents, rotaxanes as cytotoxic agents, rotaxanes as peptide transporters, mechanized silica nanoparticles as stimuli responsive drug delivery systems, and polyrotaxanes as drug and gene delivery systems.

Herein, we have fabricated a novel platform consisting of gelatin B in ionic liquid [1-ethyl- 3-methylimidazolium chloride [C2mim][Cl] (ionic liquid, IL)] formed ionogels (Ig) by dissolution method and used it for glucose detection. The ionogels were deposited onto indium tin oxide (ITO) coated glass plate using drop casting technique. Glucose oxidase (GOx) was selected as a model enzyme to investigate its interaction with Ig/ITO electrode using electrochemical and optical methods. Structural and morphological studies of the Ig/ITO electrode were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and cyclic voltmmetry before and after GOx immobilization. It was found that [C2mim][Cl] enhanced electrocatalytic behaviour of the fabricated electrode which provided electron transfer rate constant as Ks ≈ 0.113 s-1. Response study of GOx/Ig/ITO bioelectrode as a function of glucose concentration was monitored. These gelatin-ionic liquid based bioelectrodes showed following results obtained from electrochemical technique linearity ≈ 1-20 mM, and low value of Michaelis-Menten constant, Km ≈ 0.174 mM with sensitivity ≈ 4.6µA mM-1 cm-2. In contrast, the optical detection of glucose exhibited linearity in the range of 6-20 mM, value of Km ≈ 3.8 mM with sensitivity 6.76 x 10-3 Abs/mM cm2. This clearly indicated that the prepared ionogel based electrodes will provide a promising platform for glucose detection.

Among the diversity of natural and synthetic compounds being studied and applied for human welfare, peptides able to develop nanostructures are currently under special attention of scientists. In this review, we focus on such properties of peptides and various kinds of intramolecular interactions allowing their ability to form different shapes of nanoassemblies. We have also discussed the applications of self-assembled peptides in various biomedical fields where they can be employed as cargo to target delivery of drugs, genes, in tissue engineering, regenerative medicines, and biosensors.