Pasquale Longo

Biopolymeric self-assembled nanoparticles for enhanced antibacterial activity of Ag-based compounds

Microbial infections still remain one of the main issues for human health. The rapid development of resistance towards the most common antimicrobial drugs in bacteria represents today a challenge in the infections management. In the present work we have investigated the antibacterial activity of a group of compounds, namely silver N-heterocyclic carbene complexes, against a broad spectrum of bacteria. For the most promising compound, a biopolymeric nanocarrier has been developed, in order to potentiate the metal complex activity against both Gram +ve and Gram -ve. The polymeric nanovehicle is based on dextran, modified with oleic acid residues, that confer amphiphilic properties to the polysaccharide. We have characterized the obtained biomaterial and studied its ability to self-assemble into nanoparticles in aqueous environment. Next, the transdermal diffusion analyses have been carried out to evaluate the ability of the polymeric particles to penetrate tissues. Thanks to the strategy adopted, we have fabricated an antibacterial system to which K. pneumoniae and E. coli are the most sensitive.

Novel Gold and Silver Carbene Complexes Exert Antitumor Effects Triggering the Reactive Oxygen Species Dependent Intrinsic Apoptotic Pathway

Cisplatin and other platinum‐based drugs are well‐known valid anticancer drugs. However, during chemotherapy, the presence of numerous side effects and the onset of frequent phenomena of resistance has pushed many research groups to devise new metal‐based compounds holding improved anticancer properties and fewer undesired effects. Amongst the variety of synthesized compounds, significant antiproliferative effects have been obtained by employing organometallic compounds, particularly those based on silver and gold. With this in mind, we synthesized four compounds, two silver complexes and two gold complexes, with good inhibitory effects on the inu2005vitro proliferation of breast and ovarian cancer‐cell models. The antitumor activity of the most active compound, that is, AuL4, was found to be ninefold higher than that of cisplatin, and this compound induced dramatic morphological changes in HeLa cells. AuL4 induced PARP‐1 cleavage, caspasesu20053/7 and 9 activation, mitochondria disruption, cytochromeu2005c release in cancer‐cell cytoplasm, and the intracellular production of reactive oxygen species. Thus, AuL4 treatment caused cancer‐cell death by the intrinsic apoptotic pathway, whereas no cytotoxic effects were recorded upon treating non‐tumor cell lines. The reported outcomes may be an important contribution to the expanding knowledge of medicinal bio‐organometallic chemistry and enlarge the available anticancer toolbox, offering improved features, such as higher activity and/or selectivity, and opening the way to new discoveries and applications.

Phosphonium Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines

Aims/Objective: Phosphonium salts are compounds whose structural characteristics enable them to cross the plasma and mitochondrial membrane with ease. Cancer cells have higher plasma membrane potentials than normal cells; phosphonium salts selectively accumulate in the mitochondria of neoplastic cells and inhibit mitochondrial function.nnnMETHODnIn the present work, we investigated the cytotoxic activity of lipophilic phosphonium salt (11- methoxy11-oxo-undecyl) triphenylphosphonium bromide (MUTP) as well as of the two new phosphine oxide salts, 3,3-(methylphosphoryl) dibenzenaminium chloride (SBAMPO) and 3,3 (phenylphosphoryl) dibenzenaminium chloride (SBAPPO) on the proliferation of breast cancer cell line (MCF-7) and human uterin cervix adenocarcinoma cells (HeLa).nnnRESULTnWe showed that only MUTP exhibits antiproliferative effects on both cell lines, without affecting the normal breast epithelial cell proliferation. More specifically, we demonstrated that MUTP treatment of breast cancer cells is associated with impaired cell-cycle progression and metabolically induces mitochondrial damage and triggers apoptotic cell death in MCF-7 and HeLa cells. Taken together, these findings suggest that MUTP may be capable of selectively targeting neoplastic cell growth and therefore has potential applications as anticancer agent.

Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

Abstract Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib–polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50u2009kDau2009<u2009Mwu2009< 75u2009kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC50 value against MCF-7 cells.