Engineering dual-stimuli responsive poly(vinyl alcohol) nanofibrous membranes for cancer treatment by magnetic hyperthermia.

The development of new cancer treatment options, such as multifunctional devices, allows for a more personalized treatment, avoiding the known severe side effects of conventional options. In this context, on-demand drug delivery systems can actively control the rate of drug release offering a precise control of treatment. Magnetically and thermally controlled drug delivery systems have been explored as on-demand devices to treat chronic diseases and cancer tumors. In the present work, dual-stimuli responsive systems were developed by incorporating Fe3O4 magnetic nanoparticles (NPs) and poly(N-isopropylacrylamide) (PNIPAAm) microgels into electrospun polymeric fibers for application in cancer treatment. First, Fe3O4 NPs with an average diameter of 8 nm were synthesized by chemical precipitation technique and stabilized with dimercaptosuccinic acid (DMSA) or oleic acid (OA). PNIPAAm microgels were synthesized by surfactant-free emulsion polymerization (SFEP). Poly(vinyl alcohol) (PVA) was used as a fiber template originating fibers with an average diameter of 179 ± 14 nm. Stress tests of the membranes showed that incorporating both microgels and Fe3O4 NPs in electrospun fibers increases their Young's modulus. Swelling assays indicate that PVA membranes have a swelling ratio of around 3.4 (g/g) and that the presence of microgels does not affect its swelling ability. However, with the incorporation of Fe3O4 NPs, the swelling ratio of the membranes decreases. Magnetic hyperthermia assays show that a higher concentration of NPs leads to a higher heating ability. The composite membrane with the most promising results is the one incorporated with DMSA-coated NPs, since it shows the highest temperature variation, 5.1 °C. To assess the membranes biocompatibility and ability to promote cell proliferation, indirect and direct contact cell viability assays were performed, as well as cell adhesion assays. Following an extract method viability assay, all membrane designs did not reveal cytotoxic effects on dermal fibroblasts and melanoma cancer cells, after 48 h exposure and support long-term viability. The present work demonstrates the potential of dual-stimuli composite membranes for magnetic hyperthermia and may in the future be used as an alternative cancer treatment particularly in anatomically reachable solid tumors.

Burkholderia cenocepacia J2315 acyl carrier protein: a potential target for antimicrobials' development?

This work describes the isolation and characterization of an acyl carrier protein (ACP) mutant from Burkholderia cenocepacia J2315, a strain of the Burkholderia cepacia complex (Bcc). Bcc comprises at least 9 species that emerged as opportunistic pathogens able to cause life-threatening infections, particularly severe among cystic fibrosis patients. Bacterial ACPs are the donors of the acyl moiety involved in the biosynthesis of fatty acids, which play a central role in metabolism. The mutant was found to exhibit an increased ability to form biofilms in vitro, a more hydrophobic cell surface and reduced ability to colonize and kill the nematode Caenorhabditis elegans, used as a model of infection. The B. cenocepacia J2315 ACP protein is composed of 79 amino acid residues, with a predicted molecular mass and pI of 8.71kDa and 4.08, respectively. The ACP amino acid sequence was found to be 100% conserved within the genomes of the 52 Burkholderia strains sequenced so far. These data, together with results showing that the predicted structure of B. cenocepacia J2315 ACP is remarkably similar to the Escherichia coli AcpP, highlight its potential as a target to develop antibacterial agents to combat infections caused not only by Bcc species, but also by other Burkholderia species, especially B. pseudomallei and B. mallei.