Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy

Among the relevant properties of graphene derivatives, their ability of acting as an energy-converting device so as to produce heat (i.e., thermoablation and hyperthermia) was more recently taken into account for the treatment of solid tumors. In this pioneering study, for the first time, the in vitro RGO-induced hyperthermia was assessed and combined with the stimuli-sensitive anticancer effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting to a nanosystem endowed with synergic anticancer effects and high specificity. CJ-PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin. The citraconylamide pendants, used as pH reversible spacer, were exploited to further conjugate doxorubicin, whereas the alkyne moiety was orthogonally functionalized with an azido PEG-biotin derivative by copper­(II) catalyzed 1,3-dipolar cycloaddition. DSC measures, AFM, and UV spectrophotometry were employed to systematically investigate adsorption of CJ-PEGBT onto RGO and its physicochemical stability in aqueous media, demonstrating that a stable π-staked nanosystem can be obtained. In vitro tests using cancer breast cells (MCF-7) showed the ability of the RGO/CJ-PEGBT of efficiently killing cancer cells both via a selective laser beam thermoablation and hyperthermia-triggered chemotherapy. If compared with the nonbiotinylated nanosystem, including virgin RGO and the free conjugate, RGO/CJ-PEGBT is endowed with a smart combination of properties which warrant potential as an anticancer nanomedicine

When Functionalization of PLA Surfaces Meets Thiol–Yne Photochemistry: Case Study with Antibacterial Polyaspartamide Derivatives

In this work we wish to report on the covalent functionalization of polylactide (PLA) surfaces by photoradical thiol–yne to yield antibacterial surfaces. At first, hydrophilic and hydrophobic thiol fluorescent probes are synthesized and used to study and optimize the conditions of ligation on alkyne-PLA surfaces. In a second part, a new antibacterial polyaspartamide copolymer is covalently grafted. The covalent surface modification and the density of surface functionalization are evaluated by SEC and XPS analyses. No degradation of PLA chains is observed, whereas covalent grafting is confirmed by the presence of S2p and N1s signals. Antiadherence and antibiofilm activities are assessed against four bacterial strains, including Gram-negative and Gram-positive bacteria. A strong activity is observed with adherence reduction factors superior to 99.98% and biofilm formation decreased by 80%. Finally, in vitro cytocompatibility tests of the antibacterial surfaces are performed with L929 murine fibroblasts and show cell viability without promoting proliferation

Branched High Molecular Weight Glycopolypeptide With Broad-Spectrum Antimicrobial Activity for the Treatment of Biofilm Related Infections

There are few therapeutic options to simultaneously tackle <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing l-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and nonspecific perturbation of the bacterial membrane. PAA-VC has been tested against planktonic and established biofilms of reference strains <i>S. aureus</i> ATCC 25923 and <i>P. aeruginosa</i> ATCC 15442 and susceptible or antibiotic resistant clinical isolates of the above-mentioned microorganisms. MIC values observed for the conjugate (48–190 and 95–190 nM for <i>P. aeruginosa</i> and <i>S. aureus</i> strains, respectively) showed higher efficacy if compared with the free vancomycin (MICs within 1.07–4.28 μM) and colistin (MICs within 0.63–1.33 μM). Additionally, being highly biocompatible (IC₅₀ > 1000, 430, and 250 μg mL^–1 for PAA-VC, vancomycin and colistin respectively) high-dosage can be adopted for the eradication of infections in patients. This positively influences the anti-biofilm activity of the conjugate leading to a quasi-total eradication of established clinically relevant biofilms (inhibition >90% at 500 μg mL^–1). We believe that the in vitro presented data, especially the activity against established biofilms of two relevant pathogens, the high biocompatibility and the good mucoadhesion properties, would allow the use of PAA-VC as promising candidate to successfully address emerging infections