Self-assembled nanoparticles based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) were earlier proposed as a new drug delivery system. In current work, we studied antitumor activity of Amph-PVP-based self-assembled polymeric micelles covalently conjugated with the antitumor receptor-specific TRAIL variant DR5-B (P-DR5-B). The Amph-PVP polymer was synthesized by the earlier developed one-step technique (Kulikov et al., Polym. Sci. Ser. D, 2017). To stabilize Amph-PVP associates, the hydrophobic core was loaded with model substance prothionamide. For covalent conjugation with DR5-B, hydrophilic ends of polymeric chains were modified with maleimide, and a DR5-B N-terminal amino acid residue valine was mutated to cysteine (DR5-B/V114C). DR5-B/V114C was conjugated to the surface of polymeric micelles by the selective covalent interaction of N-terminal cysteine residue with maleimide on Amph-PVP.

The cytotoxicity of DR5-B-conjugated Amph-PVP polymeric nanoparticles was investigated in 3D multicellular tumor spheroids (MCTS) of human colon carcinoma HCT116 and HT29 cells, generated by the RGD-induced self-assembly technique (Akasov et al., Int. J. Pharm., 2016). In DR5-B-sensitive HCT116 MCTS, the P-DR5-B activity slightly increased compared to that of DR5-B. However in DR5-B-resistant HT29 MCTS, P-DR5-B significantly surpassed DR5-B in the antitumor activity. Thus, conjugation of DR5-B to the Amph-PVP nanoparticles enhanced its tumor cell killing capacity.

In current study we obtained a new nano-scaled delivery system based on Amph-PVP self-aggregates coated with covalently conjugated antitumor DR5-specific cytokine DR5-B. P-DR5-B overcomes DR5-B-resistance of the human colon carcinoma MCTS in vitro. This makes Amph-PVP polymeric nanoparticles a perspective versatile nano-scaled delivery system for the targeted proteins.

Active compounds encapsulation in polymeric carriers is a technology widely used as it protects and improves the physical characteristics of the active compound and controls its delivery. The effectiveness of polymeric microcapsules (MCs) depends on the barrier properties of the polymeric shell; for a given polymer the latter properties are affected by its molecular weight (MW) and crystallinity (x_c). The aim of this study was to modify the MW and x_c of the MC shells via solid state polymerization (SSP). SSP might take place in the amorphous regions of the polymer upon heating at temperatures higher than the glass transition point (T_g), but lower than the onset of melting (T_m). Poly(lactic acid) (PLA) was chosen as the polymeric carrier and coumarin 6 as the encapsulated compound. PLA is a biobased and biodegradable polymer widely used in drug loading systems, and coumarin 6 is a fluorescent hydrophobic drug that can be used as model compound.

SSP effectiveness as a post-encapsulation tool was proven for blank PLA MCs of two molecular weights (MW= 50000 g mol^-1 and 20000 g mol^-1). SSP led to a 40-50% enhancement of the weight-average molecular weight of the polymeric shell and to an enhancement, from 40 % to up to 70 %, of the mass fraction crystallinity in the case of the low MW-MCs. In an attempt to transfer the gained knowledge to the encapsulation systems, coumarin 6 loaded MCs were prepared. The average size of the MCs was measured at 502nm with a polydispersity index of 1.6 while the encapsulation efficiency was found 15 % for a drug loading of 10 %. UV-Vis measurements show that the compound was fully released after 10 days. Coumarin 6 is found to be thermally stable at temperatures used for SSP, while the study of SSP application in the case of loaded MCs is in progress.

As a metal-free abundant polymeric semiconductor, carbon nitride has numerous advantages for photo-based applications span from hydrogen evolution, CO2 reduction, ion transport, organic synthesis and organic dye degradation. In detail, graphitic carbon nitride (g-CN) synthesized from nitrogen-rich precursors via thermal polymerization resulting in efficient band gap along with tunable photoluminescence properties, enhances applied polymer supports after proper integration. Regarding that, recent publication detailed an integration process of organodispersible g-CN into highly commercialized resin called poly(styrene-co-divinylbenzene) through suspension photopolymerization is reported.¹ Moreover, surface activation of photo-active beads by endowing acid/base functionality was performed with visible light irradiation succesfully. Furtherly, successful transformation of g-CN embedded porous hydrogels from hydrophilic to hydrophobic via photoinduced surface modification based on g-CN photoactivity employing a non-toxic food additive molecule as a hydrophobization agent also performed.² Besides, subsequent pore substructuring via introducing secondary network photopolymerized within the pores was reported. The intention of this project was to mimic a water reservoir with nutrients for plants to provide a controllable releasing system by preventing water evaporation in soil applications.

Since g-CN is an organic semiconductor exhibiting sufficient charge separation under visible light illumination, a novel method for the oxidative photopolymerization of EDOT was successfully accomplished.³ Thanks to the absence of dissolved anions, so-formed neutral PEDOT is a highly viscous liquid that can be processed and post-doped easily.

Thanks for your consideration,

Best wishes

Cansu Esen

References

[1] C. Esen, M. Antonietti and B. Kumru*, J. App. Polym. Sci., 2021, 138, 50879.

[2] C. Esen and B. Kumru*, Beilstein J. Org. Chem., 2021, 17, 1323-1334.

[3] C. Esen, M. Antonietti and B. Kumru*, ChemPhotoChem, 2021, 5, 1-7.

Hydrogels have recently been increasingly studied due to their similarity to natural soft tissues. However, the stable mechanical properties and elasticity required for hydrogels used in sensing and wearable devices remain challenging. Herein, a novel 3D microporous structure hydrogel with favorable stable mechanical properties and elasticity has been developed via a simple and economical method. The good resilience (94.5%) and less residual strain (11.5%) are realized based on the results after 20 successive cycles at a strain of 300%. The elasticity of the hydrogel is achieved by varying the effective network chain density. The prepared hydrogels have stable mechanical properties and high elasticity, resulting in remarkable performance when used in sensors. The hydrogel-based sensors can accurately and consistently record human activities when used as wearable sensors. This work provides a new way to simply and effectively prepare hydrogels, which has great potential to be widely applicated in sensing and flexible devices such as health-recording sensors, wearable devices, and artificial intelligence.

In December 2019, a novel strain of coronavirus, SARS-CoV-2, was identified. Hoping to prevent transmission, many countries adopted a mandatory mask use in closed public spaces. However, most mask options display a passive-like action against COVID-19. To overcome such restrictions, this work proposes the incorporation of anti-viral essential oils (EOs) loaded onto a nanofibrous layer that can be adapted to both community and commercial masks.

Twenty EOs selected based on their antimicrobial nature were examined for the first time against the Escherichia virus MS2. The most effective were the lemongrass (LO), Niaouli (NO) and eucalyptus (ELO) with a minimum inhibitory concentration (MIC) of 356.0 mg/mL, 365.2 mg/mL and 586.0 mg/mL, respectively. Polycaprolactone (PCL) was prepared at 14 wt% in chloroform/dimethylformamide (DMF) and processed via electrospinning, with processing parameters being optimized to 23 kV, 0.7 mL/h and 26 cm. Uniform, beadless nanofibers were obtained. Mats were characterized as mechanically resilient, to endure movements arising from mask positioning, and hydrophobic in nature, to repel droplets coming from the exterior. Loading of the nanofibrous mats was accomplished via two ways: (1) physisorption and (2) by combining the EOs with the polymer solution. In both cases, EOs were loaded at 10% of MIC concentration (saturation) for 24 h. Presence of the EOs was confirmed along the mats (UV-visible). Antimicrobial testing via halo determination, verified their diffusion abilities. More importantly, time-kill kinetics testing of the loaded mats attested to the EOs capability to fight the virus MS2 even when bonded to the nanofibers at a smaller concentration than MIC. EOs-physisorbed mats were quicker in their action, while those entrapping the EOs in their polymeric matrix retained the antiviral activity of the mat for longer. Data demonstrated the potential of these EOs-loaded PCL nanofibers mats to work as COVID-19 active barriers for individual protection masks.