Preparation of Smart Surfaces Based on PNaSS@PEDOT Microspheres: Testing of E. coli Detection.

The main task of the research is to acquire fundamental knowledge about the effect of polymer structure on the physicochemical properties of films. A novel meta-material that can be used in manufacturing sensor layers was developed as a model. At the first stage, poly(sodium 4-styrenesulfonate) (PNaSS) cross-linked microspheres are synthesized (which are based on strong polyelectrolytes containing sulfo groups in each monomer unit), and at the second stage, PNaSS@PEDOT microspheres are formed. The poly(3,4-ethylenedioxythiophene) (PEDOT) shell was obtained by the acid-assisted self-polymerization of the monomer; this process is biologically safe and thus suitable for biomedical applications. The suitability of electrochemical impedance spectroscopy for E. coli detection was tested; it was revealed that the attached bacterial wall was destroyed upon application of constant oxidation potential (higher than 0.5 V), which makes the PNaSS@PEDOT microsphere particles promising materials for the development of antifouling coatings. Furthermore, under open-circuit conditions, the walls of E. coli bacteria were not destroyed, which opens up the possibility of employing such meta-materials as sensor films. Scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle, and wide-angle X-ray diffraction methods were applied in order to characterize the PNaSS@PEDOT films.

Glycopolymers for Efficient Inhibition of Galectin-3: In Vitro Proof of Efficacy Using Suppression of T Lymphocyte Apoptosis and Tumor Cell Migration.

The development of efficient galectin-3 (Gal-3) inhibitors draws attention in the field of anti-cancer therapy, especially due to the prominent role of extra- and intracellular Gal-3 in vital processes of cancerogenesis, such as immunosuppression, stimulation of tumor cells proliferation, survival, invasion, apoptotic resistance, and metastasis formation and progression. Here, by combining poly-LacNAc (Galß4GlcNAc)-derived oligosaccharides with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers, we synthesized multivalent glycopolymer inhibitors with a high potential to target extracellular and intracellular Gal-3. The inhibitory capabilities of the best conjugate in the studied series were in the nanomolar range proving the excellent Gal-3 inhibitory potential. Moreover, thorough investigation of the inhibitory effect in the biological conditions showed that the glycopolymers strongly inhibited Gal-3-induced apoptosis of T lymphocytes and suppressed migration and spreading of colorectal, breast, melanoma, and prostate cancer cells. In sum, the strong inhibitory activity toward Gal-3, combined with favorable pharmacokinetics of HPMA copolymers ensuring enhanced tumor accumulation via the enhanced permeability and retention effect, nominate the glycopolymers containing LacdiNAc-LacNAc (GalNAcß4GlcNAcß3Galß4GlcNAc) tetrasaccharide as promising tools for preclinical in anti-cancer therapy evaluation.

The transmission and toxicity of polymer-bound doxorubicin-containing exosomes derived from human adenocarcinoma cells.

Background: Exosomes are extracellular vesicles with the ability to encapsulate bioactive molecules, such as therapeutics. This study identified a new exosome mediated route of doxorubicin and poly(N-(2-hydroxypropyl)methacrylamide) (pHPMA)-bound doxorubicin trafficking in the tumor mass. Materials & methods: Exosome loading was achieved via incubation of the therapeutics with an adherent human breast adenocarcinoma cell line and its derived spheroids. Exosomes were characterized using HPLC, nanoparticle tracking analysis (NTA) and western blotting. Results: The therapeutics were successfully loaded into exosomes. Spheroids secreted significantly more exosomes than adherent cells and showed decreased viability after treatment with therapeutic-loaded exosomes, which confirmed successful transmission. Conclusion: To the best of our knowledge, this study provides the first evidence of pHPMA-drug conjugate secretion by extracellular vesicles.

Background: In cancer treatment, low-molecular-weight drugs (e.g., doxorubicin [DOX]) with a broad spectrum of side effects are commonly used. Through their conjugation with hydrophilic polymers ­ N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers ­ for example, most of the side effects can be reduced. These drug­polymer conjugates are delivered via bloodstream into the tumor. This study aimed to identify a new exosome-mediated route of DOX and polyHPMA(pHPMA)­DOX conjugates trafficking inside the tumor mass. Exosomes are small lipid membrane vesicles constitutively released from most of the cell types, including the tumor cells. Exosomes are able to encapsulate low-molecular-weight drugs. Methods: Exosomes were loaded with DOX and pHPMA-DOX in vitro via coincubation with cancer cells. Exosomes were isolated from the conditioned-cultivation medium after their release from cells and characterized (size, numbers, protein marker profiles). Results: The therapeutics were successfully loaded into exosomes and transmitted to the tumor cells. To the best of our knowledge, this is the first evidence of the pHPMA­drug conjugate secretion by exosomes.

γ-Butyrolactone Copolymerization with the Well-Documented Polymer Drug Carrier Poly(ethylene oxide)-block-poly(ε-caprolactone) to Fine-Tune Its Biorelevant Properties.

Polymeric drug carriers exhibit excellent properties that advance drug delivery systems. In particular, carriers based on poly(ethylene oxide)-block-poly(ε-caprolactone) are very useful in pharmacokinetics. In addition to their proven biocompatibility, there are several requirements for the efficacy of the polymeric drug carriers after internalization, e.g., nanoparticle behavior, cellular uptake, the rate of degradation, and cellular localization. The introduction of γ-butyrolactone units into the hydrophobic block enables the tuning of the abovementioned properties over a wide range. In this study, a relatively high content of γ-butyrolactone units with a reasonable yield of ≈60% is achieved by anionic ring-opening copolymerization using 1,5,7-triazabicyclo[4.4.0]dec-5-ene as a very efficient catalyst in the nonpolar environment of toluene with an incorporated γ-butyrolactone content of ≈30%. The content of γ-butyrolactone units can be easily modulated according to the feed ratio of the monomers. This method enables control over the rate of degradation so that when the content of γ-butyrolactone increases, the rate of degradation increases. These findings broaden the application possibilities of polyester-polyether-based nanoparticles for biomedical applications, such as drug delivery systems.