Abram M. Madiehe

Indium phosphide-based semiconductor nanocrystals and their applications

Semiconductor nanocrystals or quantum dots (QDs) are nanometer-sized fluorescent materials with optical properties that can be fine-tuned by varying the core size or growing a shell around the core. They have recently found wide use in the biological field which has further enhanced their importance. This review focuses on the synthesis of indium phosphide (InP) colloidal semiconductor nanocrystals. The two synthetic techniques, namely, the hot-injection and heating-up methods are discussed. Different types of the InP-based QDs involving their use as core, core/shell, alloyed, and doped systems are reviewed. The use of inorganic shells for surface passivation is also highlighted. The paper is concluded by some highlights of the applications of these systems in biological studies.

Imino-phosphine palladium(II) and platinum(II) complexes: Synthesis, molecular structures and evaluation as antitumor agents

The imino-phosphine ligands L1 and L2 were prepared via condensation reaction of 2-(diphenylphosphino)benzaldehyde with substituted anilines and obtained in very good yields. An equimolar reaction of L1 and L2 with either PdCl2(cod) or PtCl2(cod) gave new palladium(II) and platinum(II) complexes 1-4. The compounds were characterized by elemental analysis, IR, (1)H and (31)P NMR spectroscopy. The molecular structures of 2, 3 and 4 were confirmed by X-ray crystallography. All the three molecular structures crystallized in monoclinic C2/c space system. The coordination geometry around the palladium and platinum atoms in respective structures exhibited distorted square planar geometry at the metal centers. The complexes were evaluated in vitro for their cytotoxic activity against human breast (MCF-7) and human colon (HT-29) cancer cells, and they exhibited growth inhibitory activities and selectivity that were superior to the standard compound cisplatin.

Antitumor activity of phenylene bridged binuclear bis(imino-quinolyl)palladium(II) and platinum(II) complexes.

Antitumor effects of a known bis(imino-quinolyl)palladium(II) complex 1 and its newly synthesized platinum(II) analogue 2 were evaluated against human breast (MCF-7) and human colon (HT-29) cancer cell lines. The complexes gave cytotoxicity profiles that were better than the reference drug cisplatin. The highest cytotoxic activities were pronounced in complex 2 across the two examined cancer cell lines. Both compounds represent potential active drugs based on bimetallic complexes.

Targeted delivery using peptide-functionalised gold nanoparticles to white adipose tissues of obese rats

Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people. Current pharmacological treatment of obesity remains limited and ineffective due to systemic drug toxicity and undesirable side effects. The current epidemic raises a serious need for development of safer drugs to treat obesity. Nanotechnology-based drug delivery system for administering pharmaceutical compound to achieve therapeutic effects is currently an exciting field in cancer treatment. Drug delivery involves either modification of drug release profile, absorption, distribution and/or elimination, for the benefit of improving drug efficacy and safety. Therefore, nanotechnology holds promise in the treatment of diseases including obesity. Gold nanoparticles (GNPs) functionalised with different biomolecules have been successfully used as drug delivery, labelling and imaging tools in biomedical research. In this study, the binding-specificity and targeting ability of adipose homing peptide (AHP)-functionalised GNPs (AHP-GNPs) were evaluated using flow cytometry and inductively coupled plasma-optical emission spectroscopy. Caco-2 cells and rats fed either chow or a high-fat diet were treated with either unfunctionalised GNPs or AHP-GNPs. Cellular uptake of GNPs was detected in cells treated with AHP-GNPs and not those treated with GNPs alone. Binding of AHP to cells was both temperature- and concentration-dependent. Compared to rats treated with GNPs alone, treatment of obese rats with AHP-GNPs resulted in the targeted delivery of the GNPs to the white adipose tissue (WAT). This paper reports the successful targeting of AHP-functionalised GNPs to WAT of obese rats.

Dichlorido[2-(phenyl­imino­meth­yl)quinoline-N,N′]palladium(II)

In the title complex, [PdCl2(C16H12N2)], the PdII ion is coordinated by two N atoms [Pd—N 2.039 (2), 2.073 (2) Å] from a bidentate ligand and two chloride anions [Pd—Cl 2.2655 (7), 2.2991 (7) Å] in a distorted square-planar geometry. In the crystal, π–π interactions between the six-membered rings of the quinoline fragments [centroid–centroid distances = 3.815 (5), 3.824 (5) Å] link two molecules into centrosymmetric dimers.

Peptide-functionalized quantum dots for potential applications in the imaging and treatment of obesity

Background Obesity is a worldwide epidemic affecting millions of people. The current pharmacological treatment of obesity remains limited and ineffective due to drugs’ undesirable side effects. Hence, there is a need for novel or improved strategies for long-term therapies that will help prevent the disease progression into other chronic diseases. Nanotechnology holds the future for the treatment of obesity because of its versatility, as shown by improved drug efficiency and safety in cancer clinical trials. Nano-based drug delivery systems could potentially do the same for obesity through targeted drug delivery. This study investigated the use of peptide-functionalized quantum dots (QDs) for the imaging of prohibitin (PHB)-expressing cells in vitro and in diet-induced obese rats, which could potentially be used as nanocarriers of antiobesity drugs. Methods Cadmium (Cd)-based QDs were functionalized with an adipose homing peptide (AHP) and injected intravenously into lean and obese Wistar rats. Biodistribution of the QDs was analyzed by an IVIS® Lumina XR imaging system and inductively coupled plasma optical emission spectroscopy (ICP-OES). For in vitro studies, PHB-expressing (Caco-2 and MCF-7) and non-PHB-expressing (KMST-6 and CHO) cells were exposed to either unfunctionalized QDs (QD625) or AHP-functionalized QDs (AHP-QD625) and analyzed by fluorescence microscopy. Results AHP-QD625 accumulated significantly in PHB-expressing cells in vitro when compared with non-PHB-expressing cells. In vivo data indicated that QD625 accumulated mainly in the reticuloendothelial system (RES) organs, while the AHP-QD625 accumulated mostly in the white adipose tissues (WATs). Conclusion AHP-functionalized QDs were successfully and selectively delivered to the PHB-expressing cells in vitro (Caco-2 and MCF-7 cells) and in the WAT vasculature in vivo. This nanotechnology-based approach could potentially be used for dual targeted drug delivery and molecular imaging of adipose tissues in obese patients in real time.

Peptide-functionalized nanoparticles for the selective induction of apoptosis in target cells

AIM The study developed a prohibitin (PHB) targeted nanotherapy for selective induction of apoptosis in target cells. METHODS Gold nanoparticles (AuNPs) were bifunctionalized with adipose homing and proapoptotic peptides. The efficacy and mode of cell death induced by the AuNPs were investigated in vitro on three cancer cell lines. RESULTS The antiproliferative activity of PHB-targeted bifunctionalized AuNPs was more pronounced on cells that express the PHB receptor, and demonstrated receptor-mediated targeting and selectivity. The bifunctionalized AuNPs induced cell death by apoptosis. CONCLUSION The PHB-targeted nanotherapy under study could potentially be used for treatment of diseases that are characterized by overexpression of PHB. As such, further investigations will be conducted in vivo.

Aqueous soluble gold nanoparticle synthesis using polyethyleneimine and reduced glutathione

Abstract Gold nanoparticles (AuNPs) are considered to be ideal drug delivery vehicles for chemotherapeutic molecules due to the bio-inert nature of the colloids. Critical factors which determine the cellular internalization and intracellular localization of AuNPs are nanoparticle size as well as surface charge. Polydisperse AuNPs with a cationic surface charge, rich in primary amines would present multiple covalent molecule attachment loci and would be ideal for the delivery of chemotherapeutics which have multiple intracellular sites of action. In an adapted synthesis method, polydisperse cationic AuNPs were produced which were soluble in aqueous solution and showed high chemical stability. The synthesis was conducted in a comparative manner using polyethyleneimine (PEI) and reduced glutathione (GSH) as AuNP surface passivation ligands. Anisotropic as well as spherical morphologies were observed for the PEI passivated AuNPs, where the morphology was dependent on the ratio of reducing agent to Au3+ in solution. Only spherical morphologies were observed when GSH was used as the passivation ligand under similar conditions. The surface chemistry of the AuNPs was characterized by means of attenuated total reflectance spectroscopy and elemental composition was determined using energy dispersive X-ray spectroscopy. The PEI AuNPs surface was nitrogen rich, cationic and provided multiple covalent primary amine attachment points for downstream surface tailoring.