Recent advancements in polymer/liposome assembly for drug delivery: From surface modifications to hybrid vesicles

Liposomes are consolidated and attractive biomimetic nanocarriers widely used in the field of drug delivery. The structural versatility of liposomes has been exploited for the development of various carriers for the topical or systemic delivery of drugs and bioactive molecules, with the possibility of increasing their bioavailability and stability, and modulating and directing their release, while limiting the side effects at the same time. Nevertheless, first-generation vesicles suffer from some limitations including physical instability, short in vivo circulation lifetime, reduced payload, uncontrolled release properties, and low targeting abilities. Therefore, liposome preparation technology soon took advantage of the possibility of improving vesicle performance using both natural and synthetic polymers. Polymers can easily be synthesized in a controlled manner over a wide range of molecular weights and in a low dispersity range. Their properties are widely tunable and therefore allow the low chemical versatility typical of lipids to be overcome. Moreover, depending on their structure, polymers can be used to create a simple covering on the liposome surface or to intercalate in the phospholipid bilayer to give rise to real hybrid structures. This review illustrates the main strategies implemented in the field of polymer/liposome assembly for drug delivery, with a look at the most recent publications without neglecting basic concepts for a simple and complete understanding by the reader

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

One-step isolation and biochemical characterization of a highlyactive plant PSII monomeric core

We describe a one-step detergent solubilization protocol for isolating a highly active form of Photosystem II (PSII) from Pisum sativum L. Detailed characterization of the preparation showed that the complex was a monomer having no light harvesting proteins attached. This core reaction centre complex had, however, a range of low molecular mass intrinsic proteins as well as the chlorophyll binding proteins CP43 and CP47 and the reaction centre proteins D1 and D2. Of particular note was the presence of a stoichiometric level of PsbW, a low molecular weight protein not present in PSII of cyanobacteria. Despite the high oxygen evolution rate, the core complex did not retain the PsbQ extrinsic protein although there was close to a full complement of PsbO and PsbR and partial level of PsbP. However, reconstitution of PsbP and PsbPQ was possible. The presence of PsbP in absence of LHCII and other chlorophyll a/b binding proteins confirms that LHCII proteins are not a strict requirement for the assembly of this extrinsic polypeptide to the PSII core in contrast with the conclusion of Caffarri et al. (2009)

Easy preparation of liposome@pda microspheres for fast and highly efficient removal of methylene blue from water

Mussel-inspired chemistry was usefully exploited here with the aim of developing a high-efficiency, environmentally friendly material for water remediation. A micro-structured material based on polydopamine (PDA) was obtained by using liposomes as templating agents and was used for the first time as an adsorbent material for the removal of methylene blue (MB) dye from aqueous solutions. Phospholipid liposomes were made by extrusion and coated with PDA by self-polymerization of dopamine under simple and mild conditions. The obtained Liposome@PDA microspheres were characterized by DLS and Zeta potential analysis, TEM microscopy, and FTIR spectroscopy. The effects of pH, temperature, MB concentration, amount of Liposome@PDA, and contact time on the adsorption process were investigated. Results showed that the highest adsorption capacity was obtained in weakly alkaline conditions (pH = 8.0) and that it could reach up to 395.4 mg g−1 at 298 K. In addition, adsorption kinetics showed that the adsorption behavior fits a pseudo-second-order kinetic model well. The equilibrium adsorption data, instead, were well described by Langmuir isotherm. Thermodynamic analysis demonstrated that the adsorption process was endothermic and spontaneous (∆G0 = −12.55 kJ mol−1, ∆H0 = 13.37 kJ mol−1 ) in the investigated experimental conditions. Finally, the applicability of Liposome@PDA microspheres to model wastewater and the excellent reusability after regeneration by removing MB were demonstrated

Concerning synthesis of new biobased polycarbonates with curcumin in replacement of bisphenol a and recycled diphenyl carbonate as example of circular economy

Curcumin (CM) is a natural polyphenol well-known for its antioxidant and pharmaceutical properties, that can represent a renewable alternative to bisphenol A (BPA) for the synthesis of biobased polycarbonates (PC). In the presented strategy, preparation of the CM-based PC was coupled with chemical recycling of the fossil-based BPA polycarbonate (BPA-PC) conducting a two-steps trans-polymerization that replaces BPA monomer with CM or its tetrahydrogenated colorless product (THCM). In the first step of synthetic strategy, depolymerization of commercial BPA-PC was carried out with phenol as nucleophile, according to our previous procedure based on zinc derivatives and ionic liquids as catalysts, thus producing quantitatively diphenyl carbonate (DPC) e BPA. In the second step, DPC underwent a melt transesterification with CM or THCM monomers affording the corresponding bio-based polycarbonates, CM-PC and THCM-PC, respectively. THCM was prepared by reducing natural bis-phenol with cyclohexene as a hydrogen donor and characterized by 1H-NMR and MS techniques. Polymerization reactions were monitored by infrared spectroscopy and average molecular weights and dispersity of the two biobased polymers THCM-PC and CM-PC were determined by means of gel permeation chromatography (GPC). Optical properties of the prepared polymers were also measured

Results of patch-grafting of tissue infected by ‘Candidatus Phytoplasma pyri’ or by ‘Candidatus Phytoplasma prunorum’, respectively on pear and apricot plants cultivated in pot

Molecular analyses carried out either on the pear varieties ‘Conference’, ‘Comice’ and ‘William’ grafted on different rootstocks or on sixty-eight apricot varieties grafted on Myrobalan, showed the susceptibility of the tested combinations to 'Candidatus Phytoplasma pyri', transmitted by Cacopsylla pyri, and to 'Candidatus Phytoplasma prunorum', transmitted by Empoasca decedens, respectively. In order to find pear and/or apricot combinations immune to the associated Phytoplasma, several varieties grafted on new rootstock were tested in the period 2002-2008. 68 pear plants belonging to seven variety/rootstock combinations and 76 apricot plants belonging to seven combinations, all cultivated in pot, in greenhouse covered by anti-aphid tissue, were grafted with patches of infected tissues containing the specific phytoplasmas. Young healthy potted plants belonging to the pear combination ‘Comice’/P. communis and to the apricot combination ‘Palummella’/Myrobalan, both susceptible in open field to the associated phytoplasmas transmitted by the specific vectors, were also used and patch-grafted. Molecular analyses, carried out on nucleic acids extracted from leaf samples, to detect the presence of the pathogens, showed the pear variety ‘William’ grafted on Pyrus betulaefolia to be susceptible to 'Candidatus Phytoplasma pyri’. Neither the pear combination ‘Comice’/P. communis nor the apricot ‘Palummella’/Myrobalan 29 C, susceptible, in open field, to the associated phytoplasmas, became infected after patchgrafting under greenhouse conditions. Thus the results show that patch-grafting cannot be utilized in young potted plants for artificial transmission of these two phytoplasmas

Results of patch-grafting of tissue infected by ‘Candidatus Phytoplasma pyri’ or by ‘Candidatus Phytoplasma prunorum’, respectively on pear and apricot plants cultivated in pot

Molecular analyses carried out either on the pear varieties ‘Conference’, ‘Comice’ and ‘William’ grafted on different rootstocks or on sixty-eight apricot varieties grafted on Myrobalan, showed the susceptibility of the tested combinations to 'Candidatus Phytoplasma pyri', transmitted by Cacopsylla pyri, and to 'Candidatus Phytoplasma prunorum', transmitted by Empoasca decedens, respectively. In order to find pear and/or apricot combinations immune to the associated Phytoplasma, several varieties grafted on new rootstock were tested in the period 2002-2008. 68 pear plants belonging to seven variety/rootstock combinations and 76 apricot plants belonging to seven combinations, all cultivated in pot, in greenhouse covered by anti-aphid tissue, were grafted with patches of infected tissues containing the specific phytoplasmas. Young healthy potted plants belonging to the pear combination ‘Comice’/P. communis and to the apricot combination ‘Palummella’/Myrobalan, both susceptible in open field to the associated phytoplasmas transmitted by the specific vectors, were also used and patch-grafted. Molecular analyses, carried out on nucleic acids extracted from leaf samples, to detect the presence of the pathogens, showed the pear variety ‘William’ grafted on Pyrus betulaefolia to be susceptible to 'Candidatus Phytoplasma pyri’. Neither the pear combination ‘Comice’/P. communis nor the apricot ‘Palummella’/Myrobalan 29 C, susceptible, in open field, to the associated phytoplasmas, became infected after patchgrafting under greenhouse conditions. Thus the results show that patch-grafting cannot be utilized in young potted plants for artificial transmission of these two phytoplasmas.Keywords: Phytoplasmas, source of immunity, variety/rootstock combination, molecular tests, insect proof green-hous

Electronic nose and isotope ratio mass spectrometry in combination with chemometrics for the characterization of the geographical origin of Italian sweet cherries

Sweet cherries from two Italian regions, Apulia and Emilia Romagna, were analysed using electronic nose (EN) and isotope ratio mass spectrometry (IRMS), with the aim of distinguishing them according to their geographic origin. The data were elaborated by statistical techniques, examining the EN and IRMS datasets both separately and in combination. Preliminary exploratory overviews were performed and then linear discriminant analyses (LDA) were used for classification. Regarding EN, different approaches for variable selection were tested, and the most suitable strategies were highlighted. The LDA classification results were expressed in terms of recognition and prediction abilities and it was found that both EN and IRMS performed well, with IRMS showing better cross-validated prediction ability (91.0%); the EN–IRMS combination gave slightly better results (92.3%). In order to validate the final results, the models were tested using an external set of samples with excellent results

Lipid content in higher plants under osmotic stress

Abstract In this work, we performed investigations on the lipid content of higher plants (spinach) under hyperosmotic stress, by means of thin layer chromatography (TLC) and mass spectrometry. In particular, the experiments have been performed at different plant organization levels: whole leaves, freshly prepared protoplast suspension and mesophyll cells obtained by reformation of the cell wall from protoplast suspension. The results obtained showed that hyperosmotic stress induces changes in the phospholipid content depending on the different plant organization levels studied. All phospholipids showed an increment of their content in stressed whole leaves. In particular, phosphatidylglycerol (PG) redoubles its content by 1 h of osmotic shock. Different responses to hyperosmotic stress were reported for the other systems. In the case of protoplasts, an increment of PG, phosphatidylcholine (PC) and phosphatidylinositol (PI) together with biphosphatidylglycerol (BPG) and phosphatidylethanolamine (PE) content decreasing were observed in stressed sample. For PG, identified as PG (34:4) by elecrospray ionization mass spectrometry, the increment was of about 30%. In the case of cells, conversely, a decrease of PG content under osmotic stress was recorded. The results suggest an important role of phospholipids, in particular of PG, in the osmotic stress response

SNPs in ultraconserved elements and familial breast cancer risk

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