Polymer-metal-organic framework self-assembly (PMOFSA) as a robust one-step method to generate well-dispersed hybrid nanoparticles in water.

A new process, PMOFSA, is described here, that opens the way for the one-pot straightforward and versatile manufacture of polymer-MOF nanoparticles in water. It can be expected that this study will not only expand the scope of in situ preparation of polymer-MOF nano-objects but also inspire researchers in the field to prepare a new generation of polymer-MOF hybrid materials.

Multivalent cationic pseudopeptide polyplexes as a tool for cancer therapy.

In this study, a novel anticancer reagent based on polyplexes nanoparticles was developed. These nanoparticles are obtained by mixing negatively charged polyelectrolytes with the antitumour cationically-charged pseudopeptide N6L. Using two in vivo experimental tumor pancreatic models based upon PANC-1 and mPDAC cells, we found that the antitumour activity of N6L is significantly raised via its incorporation in polyplexed nanoparticles. Study of the mechanism of action using affinity isolation and si-RNA experiments indicated that N6L-polyplexes are internalized through their interaction with nucleolin. In addition, using a very aggressive model of pancreatic cancer in which gemcitabine, a standard of care for this type of cancer, has a weak effect on tumour growth, we observed that N6L-polyplexes administration has a stronger efficacy than gemcitabine. Biodistribution studies carried out in tumour-bearing mice indicated that N6L-polyplexes localises in tumour tissue, in agreement with its antitumour effect. These results support the idea that N6L nanoparticles could develop into a promising strategy for the treatment of cancer, especially hard-to-treat pancreatic cancers.

Self-assembly of amphiphilic liquid crystal polymers obtained from a cyclopropane-1,1-dicarboxylate bearing a cholesteryl mesogen.

We study the self-assembly of a new family of amphiphilic liquid crystal (LC) copolymers synthesized by the anionic ring-opening polymerization of a new cholesterol-based LC monomer, 4-(cholesteryl)butyl ethyl cyclopropane-1,1-dicarboxylate. Using the t-BuP(4) phosphazene base and thiophenol or a poly(ethylene glycol) (PEG) functionalized with thiol group to generate in situ the initiator during the polymerization, LC homopolymer and amphiphilic copolymers with narrow molecular weight distributions were obtained. The self-assemblies of the LC monomer, homopolymer, and block copolymers in bulk and in solution were studied by small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and transmission electron microscopy (TEM). All polymers exhibit in bulk an interdigitated smectic A (SmA(d)) phase with a lamellar period of 4.6 nm. The amphiphilic copolymers self-organize in solution into vesicles with wavy membrane and nanoribbons with twisted and folded structures, depending on concentration and size of LC hydrophobic block. These new morphologies will help the comprehension of the fascinating organization of thermotropic mesophase in lyotropic structures.

Synthesis of poly(propylene glycol)-block-polyethylenimine triblock copolymers for the delivery of nucleic acids.

LPEIs, which are efficient DNA transfection agents, were found to be far less effective for the delivery of siRNAs. Here, two amphiphilic triblock copolymers LPEI(50) -b-PPG(36) -b-LPEI(50) (2) and LPEI(14) -b-PPG(68) -b-LPEI(14) (4) have been synthesized. The transfection assays showed that compound 2 was efficient for DNA transfection whilst it was almost inactive for siRNA delivery. In contrast, polymer 4 was inefficient for DNA transfection while it showed capabilities for siRNA delivery. Taken together, our results indicate that the properties required for DNA and siRNA delivery are different. Moreover, we show that introduction of a hydrophobic segment that allows self-assembly confers siRNA delivery capacities.

Investigation of DNA condensing properties of amphiphilic triblock cationic polymers by atomic force microscopy.

Introduction of nucleic acids into cells is an important biotechnology research field which also holds great promise for therapeutic applications. One of the key steps in the gene delivery process is compaction of DNA into nanometric particles. The study of DNA condensing properties of three linear cationic triblock copolymers poly(ethylenimine-b-propylene glycol-b-ethylenimine), namely, LPEI(50)-PPG(36)-LPEI(50), LPEI(19)-PPG(36)-LPEI(19), and LPEI(14)-PPG(68)-LPEI(14), indicates that proper DNA condensation is driven by both the charge and the size of the respective cationic hydrophilic linear polyethylenimine (LPEI) and neutral hydrophobic poly(propylene glycol) (PPG) parts. Atomic force microscopy was used to investigate the interactions of the triblock copolymers with plasmid DNA at the single molecule level and to enlighten the mechanism involved in DNA condensation.

Synthesis of linear polyamines with different amine spacings and their ability to form dsDNA/siRNA complexes suitable for transfection.

In this paper we report on the synthesis of diversified linear polyamine architectures with different chain lengths and compositions and their interaction with phosphate groups of DNA/siRNA. The polyplex formation between model nucleotide (dsDNA) and these linear polyamines has been determined at different nitrogen to phosphorus (N/P) ratios using small-angle neutron scattering (SANS) and atomic force microscopy (AFM) techniques. AFM images showed that while linear poly(ethylene imine) (PEI)/DNA complex results in bigger spherical aggregates, poly(propylene imine)s forms torroid and cigar shaped structures upon complexation with DNA. The poly(butylene imine)s (LPBI)s form compact and soluble DNA complexes with a radii range of R(g) = 15-30 nm. Among the studied linear polyamines, the LPBIs did show the best transfection efficiency.

Amphiphilic poly[(propylene glycol)-block-(2-methyl-2-oxazoline)] copolymers for gene transfer in skeletal muscle.

Amphiphilic triblock copolymers such as poly(ethylene glycol-b-propylene glycol-b-ethylene glycol) PE6400 (PEG(13)-PPG(30)-PEG(13)) have been recently shown to promote gene transfer in muscle. Herein we investigated the effect of a chemical change of the PEG moiety on the transfection activity of these compounds. We synthesized new amphiphilic copolymers in which the PEG end blocks are replaced by more hydrophilic poly(2-methyl-2-oxazoline) (PMeOxz) chains of various lengths. The resulting triblock PMeOxz-PPG-PMeOxz compounds were characterized by NMR, SEC, TGA, and DSC techniques and assayed for in vivo muscle gene transfer. The results confirm both the block structure and the monomer unit composition (DP(PG)/DP(MeOxz)) of the new PPG(34)-PMeOxz(41) and PPG(34)-PMeOxz(21) triblock copolymers. Furthermore, in vivo experiments show that these copolymers are able to significantly increase DNA transfection efficiency, despite the fact that their chemical nature and hydrophilic character are different from the poloxamers. Overall, these results show that the capacity to enhance DNA transfection in skeletal muscle is not restricted to PEG-PPG-PEG arrangements.

Synthesis of linear polyethylenimine derivatives for DNA transfection.

A series of linear polymers containing varying amounts of ethylenimine or N-propylethylenimine units were synthesized by hydrolysis and/or reduction of polyethyloxazolines. The pK(a)s of the polyamines were determined potentiometrically. Gel mobility shift assay showed that the efficiency of DNA complexation was related to the fraction of amino groups that are protonated at neutral pH. The effects of cationic charge density and molar weight of the polymers on the transfection efficiency were evaluated on HepG2 cells. The results obtained with different copolymers show that the transfection efficiency primarily depends on the fraction of ethylenimine units included in the polymer albeit the molar weight is also of importance. On the basis of the results obtained with poly(N-propylethylenimines), we also demonstrate that the high transfection efficiency of polyethylenimines does not solely rely on their capacity to capture protons which are transferred into the endo-lysosomes during acidification.