Project description:Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy while maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, is a winning choice to ensure a long circulation and colloidal stability, while in some cases, patients could develop PEG-directed immunoglobulins after the first administration. This lead to a phenomenon called accelerated blood clearance (ABC effect), and it is correlated with clinical failure because of the premature removal of the nanosystem from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility, and its GRAS status, the natural polysaccharide inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-g-poly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physicochemical point of view (solubility, 1D and 2D NMR, FT-IR, UV-Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well-known and well-characterized PEGylated counterpart, polyethylene glycol-b-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues.
Project description:Nanoparticles designed for biomedical applications are often coated with polymers containing reactive functional groups, such as -COOH and -NH2, to conjugate targeting ligands or drugs. However, introducing highly charged surfaces promotes binding of the nanoparticles to biomolecules in biological systems through ionic interactions, causing the nanoparticles to aggregate in biological environments and consequently undergo strong non-specific binding to off-target cells and tissues. Developing a unique polymer with neutral surfaces that can be further functionalized directly would be critical to develop suitable nanomaterials for nanomedicine. Here, we report a thiol-reactive amphiphilic block copolymer poly(ethylene oxide)-block-poly(pyridyldisulfide ethylmeth acrylate) (PEO-b-PPDSM) for coating gold nanoparticles (AuNPs). The resultant polymer-coated AuNPs have almost neutral surfaces with slightly negative zeta potentials from -10 to 0 mV over a wide pH range from 2 to 12. Although the zeta potential is close to zero we show that the PEO-b-PPDSM copolymer-coated AuNPs have both good stability in various physiological conditions and reduced non-specific adsorption of proteins/biomolecules. Because of the multiple pyridyldisulfide groups on the PPDSM block, these individually dispersed nanocomplexes with an overall hydrodynamic size around 43.8 nm can be directly functionalized via disulfide-thiol exchange chemistry.
Project description:Stimuli-responsive polymers are arguably the most widely considered systems for a variety of applications in biomedical arena. We report here a novel triple stimuli sensitive block copolymer assembly that responds to changes in temperature, pH and redox potential. Our block copolymer design constitutes an acid-sensitive THP-protected HEMA as the hydrophobic part and a temperature-sensitive PNIPAM as the hydrophilic part with an intervening disulfide bond. The micellar properties and the release kinetics of the encapsulated guest molecule in response to one stimulus as well as combinations of stimuli have been evaluated. Responsiveness to combination of stimuli not only allows for fine-tuning the guest molecule release kinetics, but also provides the possibility of achieving location-specific delivery.
Project description:Three-component molecular brushes with a polyimide backbone and amphiphilic block copolymer side chains with different contents of the "inner" hydrophilic (poly(methacrylic acid)) and "outer" hydrophobic (poly(methyl methacrylate)) blocks were synthesized and characterized by molecular hydrodynamics and optics methods in solutions of chloroform, dimethylformamide, tetrahydrofuran and ethanol. The peculiarity of the studied polymers is the amphiphilic structure of the grafted chains. The molar masses of the molecular brushes were determined by static and dynamic light scattering in chloroform in which polymers form molecularly disperse solutions. Spontaneous self-assembly of macromolecules was detected in dimethylformamide, tetrahydrofuran and ethanol. The aggregates size depended on the thermodynamic quality of the solvent as well as on the macromolecular architectural parameters. In dimethylformamide and tetrahydrofuran, the distribution of hydrodynamic radii of aggregates was bimodal, while in ethanol, it was unimodal. Moreover, in ethanol, an increase in the poly(methyl methacrylate) content caused a decrease in the hydrodynamic radius of aggregates. A significant difference in the nature of the blocks included in the brushes determines the selectivity of the used solvents, since their thermodynamic quality with respect to the blocks is different. The macromolecules of the studied graft copolymers tend to self-organization in selective solvents with formation of a core-shell structure with an insoluble solvophobic core surrounded by the solvophilic shell of side chains.
Project description:Poly(dimethylsiloxane)-block-methoxypolyethylene glycols (PDMS-b-mPEG) were synthesized by Steglich esterification. The high-permeable membrane (PSf/PDMS-b-mPEG) was prepared by using PDMS-b-mPEG as additives. The successful synthesis of PDMS-b-mPEG was confirmed by nuclear magnetic resonance. Field emission scanning electron microscopy images show that the distribution of finger-like macroporous and sponge-like macroporous can be modulated by controlling the ratio of the hydrophilic/hydrophobic components of additives. The distribution of additives and membrane wettability are validated with X-ray photoelectron spectroscopy and water contact angle test. The permeability of the blended membrane, especially for the membrane PSf/PDMS-b-mPEG1900 (M3), was remarkably improved. The water permeability of M3 (239.4 L/m2·h·bar) was 6.6 times that of the unblended membrane M0 (42.5 L/m2·h·bar). The findings of protein BSA filtration show that the flux recovery ratio of M3 is 89.2% at a BSA retention rate of about 80%, which demonstrates that the polysulfone membranes blended with PDMS-b-mPEG have excellent antifouling performance and extraordinary permeability.
Project description:Polyethylene-b-polypeptide copolymers are biologically interesting, but studies of their synthesis and properties are very few. This paper reports synthesis and characterization of well-defined amphiphilic polyethylene-block-poly(L-lysine) (PE-b-PLL) block copolymers by combining nickel-catalyzed living ethylene polymerization with controlled ring-opening polymerization (ROP) of ε-benzyloxycarbonyl-L-lysine-N-carboxyanhydride (Z-Lys-NCA) and sequential post-functionalization. Amphiphilic PE-b-PLL block copolymers self-assembled into spherical micelles with a hydrophobic PE core in aqueous solution. The pH and ionic responsivities of PE-b-PLL polymeric micelles were investigated by means of fluorescence spectroscopy, dynamic light scattering, UV-circular dichroism, and transmission electron microscopy. The variation of pH values led to the conformational alteration of PLL from α-helix to coil, thereby changing the micelle dimensions.
Project description:Iron oxide nanoparticles (NPs) with diameters of 16.1, 20.5, and 20.8 nm prepared from iron oleate precursors were coated with poly(maleic acid-alt-1-octadecene) (PMAcOD). The coating procedure exploited hydrophobic interactions of octadecene and oleic acid tails while hydrolysis of maleic anhydride moieties allowed the NP hydrophilicity. The PMAcOD nanostructure in water and the PMAcOD-coated NPs were studied using transmission electron microscopy, zeta-potential measurements, small-angle X-ray scattering, and fluorescence measurements. The combination of several techniques suggests that independently of the iron oxide core and oleic acid shell structures, PMAcOD encapsulates NPs, forming stable hydrophilic shells which withstand absorption of hydrophobic molecules, such as pyrene, without shell disintegration. Moreover, the PMAcOD molecules are predominantly attached to a single NP instead of self-assembling into the PMAcOD disklike nanostructures or attachment to several NPs. This leads to highly monodisperse aqueous samples with only a small fraction of NPs forming large aggregates due to cross-linking by the copolymer macromolecules.
Project description:There is an emerging need to evolve the conventional lyotropic liquid crystalline nanoparticles to advanced stimuli-responsive, therapeutic nanosystems with upgraded functionality. Towards this effort, typically used stabilizers, such as Pluronics®, can be combined or replaced by smart, stimuli-responsive block copolymers. The aim of this study is to incorporate the stimuli-responsive amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) as a stabilizer in lipidic liquid crystalline nanoparticles, in order to provide steric stabilization and simultaneous stimuli-responsiveness. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by light scattering techniques, cryogenic-transmission electron microscopy (cryo-TEM), X-ray diffraction (XRD) and fluorescence spectroscopy. The PDMAEMA-b-PLMA, either individually or combined with Poloxamer 407, exhibited different modes of stabilization depending on the lipid used. Due to the protonation ability of PDMAEMA blocks in acidic pH, the nanoparticles exhibited high positive charge, as well as pH-responsive charge conversion, which can be exploited towards pharmaceutical applications. The ionic strength, temperature and serum proteins influenced the physicochemical behavior of the nanoparticles, while the polymer concentration differentiated their morphology; their micropolarity and microfluidity were also evaluated. The proposed liquid crystalline nanosystems can be considered as novel and attractive pH-responsive drug and gene delivery nanocarriers due to their polycationic content.
Project description:Here we report a novel poly(2-oxazoline)-based block copolymer with the aromatic heterocyclic side chains in one block, poly(2-methyl-2-oxazoline)-b-poly(2-N,N-dimethyl-1,3,5-triazine-2,4-diamine-6-ethyl-2-oxazoline) (PMeOx-PcBOx), and demonstrate its potential application as a drug delivery platform. The copolymer was synthesized via the condensation of N,N-dimethylbiguanide with the methyl ester side chain in poly(2-methoxycarboxyethyl-2-oxazoline) block (PMestOx) of the PMeOx-PMestOx diblock copolymer. We confirmed the N,N-dimethylbiguanide condensation with PMestOx and the complete conversion of the side chain to the N,N-dimethyl-1,3,5-triazine-2,4-diamine-6-ethyl moiety by NMR spectroscopy, MALDI-TOF mass spectroscopy, UV-Vis spectroscopy, and titration analysis. The PMeOx-PcBOx copolymer self-assemble into polymeric micelles in aqueous solution. Successful encapsulation into these micelles has been demonstrated for 1) several poorly soluble drugs, such as bruceantin and LY2109761, and 2) dichloro(1,2-diaminocyclohexane)platinum(II) (DachPt). The first class of drugs is incorporated possibly via hydrogen bonding and pi-pi interactions with the PcBOx side groups, while the second one is likely forms coordination bonds with the same side groups. The capability of this new copolymer to solubilize a uniquely diverse set of active pharmaceutical ingredients suggests potential applications in drug delivery.
Project description:Biomimetic lipid membranes on solid supports have been used in a plethora of applications, including as biosensors, in research on membrane proteins or as interfaces in cell experiments. For many of these applications, structured lipid membranes, e.g., in the form of arrays with features of different functionality, are highly desired. The stability of these features on a given substrate during storage and in incubation steps is key, while at the same time the substrate ideally should also exhibit antifouling properties. Here, we describe the highly beneficial properties of a 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer for the stability of supported lipid membrane structures generated by dip-pen nanolithography with phospholipids (L-DPN). The MPC copolymer substrates allow for more stable and higher membrane stack structures in comparison to other hydrophilic substrates, like glass or silicon oxide surfaces. The structures remain highly stable under immersion in liquid and subsequent incubation and washing steps. This allows multiplexed functionalization of lipid arrays with antibodies via microchannel cantilever spotting (µCS), without the need of orthogonal binding tags for each antibody type. The combined properties of the MPC copolymer substrate demonstrate a great potential for lipid-based biomedical sensing and diagnostic platforms.