Synergistic effect of folate-conjugated polymers and 5-fluorouracil in the treatment of colon cancer

Background In recent years, targeted drug delivery strategies have received special attention from the scientific world due to advantages such as more effective therapy and reduction of side effects. The principle of operation is delayed excretion from the bloodstream of the drug delivery system compared to the drug itself, as well as facilitated penetration into diseased cells thanks to the use of ligands recognized by appropriate receptors. Particularly interesting drug carriers are amphiphilic copolymers that form nano-sized micelles with a drug, which can release the drug at a specific place in the body under the influence of appropriate stimuli. Results We describe the synthesis of the diblock polymer, poly(2-hydroxyethyl acrylate)-b-poly(N-vinylcaprolactam) using RAFT/MADIX (Reversible Addition-Fragmentation chain Transfer/MAcromolecular Design by Interchange of Xanthate) controlled polymerization affording polymers with good dispersity according to SEC (Size-Exclusion Chromatography). Some post-modifications of the polymer with folic acid were then performed as evidenced by NMR (Nuclear Magnetic Resonance), UV–Vis (UltraViolet–Visible) and FT-IR (Fourier-Transform Infrared) spectroscopy, and TGA (ThermoGravimetric Analysis). The formation of stable micellar systems from polymers with and without the drug, 5-fluorouracil, was confirmed by DLS (Dynamic Light Scattering) and zeta potential measurements, and TEM (Transmission Eelectron Microscopy) imaging. Finally, the cloud point of the polymers was investigated, which turned out to be close to the temperature of the human body. Most importantly, these micellar systems have been explored as a drug delivery system against colon cancer, showing increased cytotoxicity compared to the drug alone. This effect was achieved due to the easier cellular uptake by the interaction of folic acid and its receptors on the surface of cancer cells. Conclusions The presented results constitute a solid foundation for the implementation of a nano-sized drug delivery system containing folic acid for practical use in the treatment of drug-resistant cancer, as well as more effective therapy with fewer side effects. Graphical Abstract

Helical Polycarbenes Bearing D-Prolinol Ester Pendants: An Efficient Catalyst for Asymmetric Michael Addition Reaction

a novel diazoacetate monomer (1) carrying tert-butyloxycarboryl (Boc) protected D-prolinol ester was designed and synthesized successfully. Molecular weight-controlled polymerization of 1 using the complex of π-allylPdCl coordinated Wei-phos (LR) ligand gives a series of helical polycarbenes (poly-1ms) with well-defined molecular weights (Mns) and low polydispersity (Mw/Mns). Removing the protecting Boc groups on the D-prolinol ester pendants leads to the formation of helical poly-1m-As, which showed high optical activity. Furthermore, the poly-1m-As showed high catalytic ability on asymmetric Michael addition reaction (up to 76% ee and 94/6 dr). Both the enantioselectivity and diastereoselectivity of the Michael addition reaction were increased comparing to D-prolinol as catalyst. Moreover, the helical polycarbene catalyst can be easily recovered and reused at least four times without significant loss of its enantioselectivity and diastereoselectivity.

Synthesis of Poly(methacrylic acid)-block-Polystyrene Diblock Copolymers at High Solid Contents via RAFT Emulsion Polymerization

The combination of polymerization–induced self-assembly (PISA) and reversible–addition fragmentation chain transfer (RAFT) emulsion polymerization offers a powerful technique to synthesize diblock copolymers and polymeric nanoparticles in a controlled manner. The RAFT emulsion diblock copolymerization of styrene and methacrylic acid (MAA) by using a trithiocarbonate as surfactant and RAFT agent was investigated. The Z-group of the RAFT agent was modified with a propyl-, butyl- and dodecyl- sidechain, increasing the hydrophobicity of the RAFT agent to offer well-controlled polymerization of poly(methacrylic acid)-block-polystyrene (PMAA-b-PS) diblock copolymers at high solid contents between 30–50 wt% in water. The kinetic data of the PMAA homopolymerization with the three different RAFT agents for various solvents was investigated as well as the RAFT emulsion polymerization of the diblock copolymers in pure water. While the polymerization of PMAA-b-PS with a propyl terminus as a Z-group suffered from slow polymerization rates at solid contents above 30 wt%, the polymerization with a dodecyl sidechain as a Z-group led to full conversion within 2 h, narrow molar mass distributions and all that at a remarkable solid content of up to 50 wt%.

Controlling Molecular Aggregation-Induced Emission by Controlled Polymerization

In last twenty years, the significant development of AIE materials has been witnessed. A number of small molecules, polymers and composites with AIE activity have been synthesized, with some of these exhibiting great potential in optoelectronics and biomedical applications. Compared to AIE small molecules, macromolecular systems—especially well-defined AIE polymers—have been studied relatively less. Controlled polymerization methods provide the efficient synthesis of well-defined AIE polymers with varied monomers, tunable chain lengths and narrow dispersity. In particular, the preparation of single-fluorophore polymers through AIE molecule-initiated polymerization enables the systematic investigation of the structure–property relationships of AIE polymeric systems. Here, the main polymerization techniques involved in these polymers are summarized and the key parameters that affect their photophysical properties are analyzed. The author endeavored to collect meaningful information from the descriptions of AIE polymer systems in the literature, to find connections by comparing different representative examples, and hopes eventually to provide a set of general guidelines for AIE polymer design, along with personal perspectives on the direction of future research.

Polystyrene-b-Poly(2-(Methoxyethoxy)ethyl Methacrylate) Polymerization by Different Controlled Polymerization Mechanisms

Functional polymers have been an important field of research in recent years. With the development of the controlled polymerization methods, block-copolymers of defined structures and properties could be obtained. In this paper, the possibility of the synthesis of the functional block-copolymer polystyrene-b-poly(2-(methoxyethoxy)ethyl methacrylate) was tested. The target was to prepare the polymer of the number average molecular weight (Mn) of approximately 120 that would contain 20–40% of poly(2-(methoxyethoxy)ethyl methacrylate) by mass and in which the polymer phases would be separated. The polymerization reactions were performed by three different mechanisms for the controlled polymerization—sequential anionic polymerization, atomic transfer radical polymerization and the combination of those two methods. In sequential anionic polymerization and in atomic transfer radical polymerization block-copolymers of the desired composition were obtained but with the Mn significantly lower than desired (up to 30). The polymerization of the block-copolymers of the higher Mn was unsuccessful, and the possible mechanisms for the unwanted side reactions are discussed. It is also concluded that combination of sequential anionic polymerization and atomic transfer radical polymerization is not suitable for this system as polystyrene macroinitiator cannot initiate the polymerization of poly(2-(methoxyethoxy)ethyl methacrylate).

Thiol-Lactam Initiated Radical Polymerization (TLIRP): Scope and Application for the Surface Functionalization of Nanoparticles

: Controlled polymerization techniques make possible fabrication of polymers with desired molecular weights, narrow dispersity, and also tailor-making of advanced hybrid materials. Thiol-Lactam Initiated Radical Polymerization (TLIRP) was introduced in 2002 and developed during the last two decades. The thiol/lactam combination enables one to generate radicals that can initiate the polymerization of vinyl-based monomers. The study of the mechanism and kinetics of TLIRP revealed the characteristics of living polymerization for TLIRP. Moreover, TLIRP has been used successfully for the synthesis of homopolymers, block copolymers, and statistical copolymers with polydispersity below 2.0. Especially, TLIRP provides a very straightforward method for grafting polymer brushes on the surface of nanoparticles. We review herein the systems developed for TLIRP and their applications for macromolecular engineering, with an emphasis on the surface functionalization of nanoparticles via the grafting-from approach.

The Role of Polymer Structure in Formation of Various Nano- and Microstructural Materials: 30 Years of Research in the Laboratory of Nano- and Microstructural Materials at the Centre of Polymer and Carbon Materials PAS

The review summarizes the research carried out in the Laboratory of Nano- and Microstructural Materials at the Centre of Polymer and Carbon Materials, Polish Academy of Sciences (CMPW PAS). Studies carried out for many years under the guidance of Professor Andrzej Dworak led to the development and exploration of the mechanisms of oxirane and cyclic imine polymerization and controlled radical polymerization of methacrylate monomers. Based on that knowledge, within the last three decades, macromolecules with the desired composition, molar mass and topology were obtained and investigated. The ability to control the structure of the synthesized polymers turned out to be important, as it provided a way to tailor the physiochemical properties of the materials to their specific uses. Many linear polymers and copolymers as well as macromolecules with branched, star, dendritic and hyperbranched architectures were synthesized. Thanks to the applied controlled polymerization techniques, it was possible to obtain hydrophilic, hydrophobic, amphiphilic and stimulus-sensitive polymers. These tailor-made polymers with controlled properties were used for the construction of various types of materials, primarily on the micro- and nanoscales, with a wide range of possible applications, mainly in biomedicine. The diverse topology of polymers, and thus their properties, made it possible to obtain various types of polymeric nanostructures and use them as nanocarriers by encapsulation of biologically active substances. Additionally, polymer layers were obtained with features useful in medicine, particularly regenerative medicine and tissue engineering.