Doxorubicin nanoformulations on therapy against cancer: An overview from the last 10 years.

Doxorubicin (DOX) is a natural antibiotic with antineoplastic activity. It has been used for over 40 years and remains one of the most used drugs in chemotherapy for a variety of cancers. However, cardiotoxicity limits its use for long periods. To overcome this limitation, encapsulation in smart drug delivery systems (DDS) brings advantages in comparison with free drug administration (i.e., conventional anticancer drug therapy). In this review, we present the most relevant nanostructures used for DOX encapsulation over the last 10 years, such as liposomes, micelles and polymeric vesicles (i.e., polymersomes), micro/nanoemulsions, different types of polymeric nanoparticles and hydrogel nanoparticles, as well as novel approaches for DOX encapsulation. The studies highlighted here show these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged DOX release, as well as reduced side effects, among other interesting advantages.

Biohybrid microswimmers against bacterial infections.

Biohybrid microswimmers exploit the natural abilities of motile microorganisms e.g. in releasing cargo on-demand. However, using such engineered swarms to release antibiotics addressing bacterial infections has not yet been realized. Herein, a design strategy for biohybrid microswimmers is reported, which features the covalent attachment of antibiotics with a photo-cleavable linker to the algae Chlamydomonas reinhardtii via two synthetic steps. This surface engineering does not rely on genetic manipulations, proceeds with high efficiency, and retains the viability or phototaxis of microalgae. Two different antibiotics have been separately utilized, which result in activity against both gram-positive and gram-negative strains. Guiding the biohybrid microswimmers by an external beacon, and on-demand delivery of the drugs by light with high spatial and temporal control, allowed for strong inhibition of bacterial growth. This efficient strategy could potentially allow for the selective treatment of bacterial infections by engineered algal microrobots with high precision in space and time. STATEMENT OF SIGNIFICANCE: Biological swimmers with innate sensing and actuation capabilities and integrated components have been widely investigated to create autonomous microsystems. The use of natural swimmers as cargo delivery systems presents an alternative strategy to transport therapeutics to the required locations with the difficult access by traditional strategies. Although the transfer of various therapeutic cargo has shown promising results, the utilization of microswimmers for the delivery of antimicrobials was barely covered. Therefore, we present biohybrid microalga-powered swimmers designed and engineered to carry antibiotic cargo against both Gram-positive and Gram-negative bacteria. Guided by an external beacon, these microhybrids deliver the antibiotic payload to the site of bacterial infection, with high spatial and temporal precision, released on-demand by an external trigger to inhibit bacterial growth.

Heterologous expression and purification of active L-asparaginase I of Saccharomyces cerevisiae in Escherichia coli host.

l-asparaginase (ASNase) is a biopharmaceutical widely used to treat child leukemia. However, it presents some side effects, and in order to provide an alternative biopharmaceutical, in this work, the genes encoding ASNase from Saccharomyces cerevisiae (Sc_ASNaseI and Sc_ASNaseII) were cloned in the prokaryotic expression system Escherichia coli. In the 93 different expression conditions tested, the Sc_ASNaseII protein was always obtained as an insoluble and inactive form. However, the Sc_ASNaseI (His)6 -tagged recombinant protein was produced in large amounts in the soluble fraction of the protein extract. Affinity chromatography was performed on a Fast Protein Liquid Chromatography (FPLC) system using Ni2+ -charged, HiTrap Immobilized Metal ion Affinity Chromatography (IMAC) FF in order to purify active Sc_ASNaseI recombinant protein. The results suggest that the strategy for the expression and purification of this potential new biopharmaceutical protein with lower side effects was efficient since high amounts of soluble Sc_ASNaseI with high specific activity (110.1 ± 0.3 IU mg-1 ) were obtained. In addition, the use of FPLC-IMAC proved to be an efficient tool in the purification of this enzyme, since a good recovery (40.50 ± 0.01%) was achieved with a purification factor of 17-fold. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:416-424, 2017.