Mushrooms of the genus Ganoderma are known for diverse biological activities, demonstrated both traditionally and experimentally. Their secondary metabolites have shown cytotoxic potential across different cancer cell lines. Besides exploration of the most active components in different species or genotypes, new formulation techniques are in development. In recent years, there has been a growing interest in the use of nanomaterials because of significant potential for pharmacology applications as substance carriers. Applying nanoparticles may enhance the medicinal effect of the mushroom substances. This study investigated the cytotoxic properties of Ganoderma species methanolic extracts against the HeLa cancer cell line. Notably, the extract obtained from Ganoderma pfeifferi demonstrated the highest activity and was further used for encapsulation within synthesized mesoporous silica nanoparticles MCM-41. Subsequently, the cytotoxic effect of the loaded MCM-41 to the free form of extract was compared. The obtained results indicate successful encapsulation, and similar activity comparing encapsulated form to free extracts (IC50 16.6 μg/mL and 20.5 μg/mL, respectively). In addition, the four unique compounds were identified as applanoxidic acid A, applanoxidic acid G, ganoderone A, and ganoderone B in the G. pfeifferi. This study is an essential prerequisite for further steps like nanoparticle functionalization for sustained or on-command delivery of these natural extracts.

• Klíčová slova
• HeLa, antiproliferative activity, applanoxidic acids, bioactivity, reishi mushroom,
• Publikační typ
• časopisecké články MeSH

This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and 1H NMR spectroscopy, were used to characterize the block copolymers, while 1H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications.

• Klíčová slova
• DLS, LCST, NMR, NOESY, PLA, RAFT-ROP, TEGMA, drug release, thermo-responsive polymer,
• Publikační typ
• časopisecké články MeSH

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

• Klíčová slova
• LCST, biodistribution, poly(2,2-difluoroethyl)acrylamide, poly(N,N-diethylacrylamide), poly(N-acryloylpyrolidine), poly(N-isopropylacrylamide), polyacrylamide, rational polymer design,
• MeSH
• myši MeSH
• polymery * MeSH
• teplota MeSH
• tkáňová distribuce MeSH
• uvolňování léčiv MeSH
• voda * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• polymery * MeSH
• voda * MeSH

Over the last few years, the development and relevance of 19F magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of 19F MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of 19F MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy.

• Klíčová slova
• 19F MRI probe, Fluorine, Magnetic resonance imaging (MRI), Molecular imaging, Polymer,
• MeSH
• fluor chemie   MeSH
• fluorokarbony chemie   MeSH
• koncentrace vodíkových iontů MeSH
• kontrastní látky chemie   MeSH
• lidé MeSH
• molekulární sondy chemie   MeSH
• molekulární zobrazování přístrojové vybavení   metody   MeSH
• myši MeSH
• polymery chemie   MeSH
• radiační rozptyl MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• světlo MeSH
• teplota MeSH
• zobrazování fluorovou magnetickou rezonancí metody   trendy   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fluor MeSH
• fluorokarbony MeSH
• kontrastní látky MeSH
• molekulární sondy MeSH
• polymery MeSH
• reaktivní formy kyslíku MeSH

Poly(N-isopropylacrylamide) (PNIPAM) is an important polymer with stimuli-responsive properties, making it suitable for various uses. Phase behavior of the temperature-sensitive PNIPAM polymer in the presence of four low-molecular weight additives tert-butylamine (t-BuAM), tert-butyl alcohol (t-BuOH), tert-butyl methyl ether (t-BuME), and tert-butyl methyl ketone (t-BuMK) was studied in water (D2O) using high-resolution nuclear magnetic resonance (NMR) spectroscopy and dynamic light scattering. Phase separation was thermodynamically modeled as a two-state process which resulted in a simple curve which can be used for fitting of NMR data and obtaining all important thermodynamic parameters using simple formulas presented in this paper. The model is based on a modified van't Hoff equation. Phase separation temperatures T p and thermodynamic parameters (enthalpy and entropy change) connected with the phase separation of PNIPAM were obtained using this method. It was determined that T p is dependent on additives in the following order: T p(t-BuAM) > T p(t-BuOH) > T p(t-BuME) > T p(t-BuMK). Also, either increasing the additive concentration or increasing pK a of the additive leads to depression of T p. Time-resolved 1H NMR spin-spin relaxation experiments (T 2) performed above the phase separation temperature of PNIPAM revealed high colloidal stability of the phase-separated polymer induced by the additives (relative to the neat PNIPAM/D2O system). Small quantities of selected suitable additives can be used to optimize the properties of PNIPAM preparations including their phase separation temperatures, colloidal stabilities, and morphologies, thus improving the prospects for the application.

• Publikační typ
• časopisecké články MeSH