Vesicles were made from amphiphilic diblock copolymers and characterized by micromanipulation. The average molecular weight of the specific polymer studied, polyethyleneoxide-polyethylethylene (EO40-EE37), is several times greater than that of typical phospholipids in natural membranes. Both the membrane bending and area expansion moduli of electroformed polymersomes (polymer-based liposomes) fell within the range of lipid membrane measurements, but the giant polymersomes proved to be almost an order of magnitude tougher and sustained far greater areal strain before rupture. The polymersome membrane was also at least 10 times less permeable to water than common phospholipid bilayers. The results suggest a new class of synthetic thin-shelled capsules based on block copolymer chemistry.

A low molecular weight poly(ethyleneoxide)-poly(butadiene) (PEO-PB) diblock copolymer containing 50 weight percent PEO forms gigantic wormlike micelles at low concentrations (<5 percent by weight) in water. Subsequent generation of free radicals with a conventional water-based redox reaction leads to chemical cross-linking of the PB cores without disruption of the cylindrical morphology, as evidenced by cryotransmission electron microscopy and small-angle neutron scattering experiments. These wormlike rubber micelles exhibit unusual viscoelastic properties in water.

We investigated the micellar polymorphism of poly(ethylene oxide)(PEO)-based block copolymers to illustrate the possibility of a rational control of the aggregation structure through synthetic manipulation of the molecular characteristics. Boundaries for the micellar shape transitions from bilayers to cylinders to spheres with increasing PEO composition were determined with direct cryogenic transmission electron microscopic (cryo-TEM) imaging of the microstructures in the form of thin vitreous hydrated specimens. Analyses of cryo-TEM images lead to determination of the packing properties of the hydrophobic block in terms of the interfacial area per chain and the degree of chain stretching. Also, the micellar phases of the block copolymers are characterized by anomalous structural behaviors such as coexistence of different structures and formation of exotic compound structures, which are discussed in terms of metastability inherent in the system comprising polymeric materials.

Massively cross-linked and property-tunable membranes have been fabricated by free radical polymerization of self-assembled, block copolymer vesiclespolymersomes. Similar efforts with cross-linkable lipids would appear frustrated in the past due to at least two factors: limited reactivity and membrane fragility under local stresses of nano-confined cross-linking. We describe here a diblock copolymer of poly(ethylene oxide)polybutadiene that has a hydrophilic weight fraction like that of lipids and forms robust fluid phase membranes in water. The polymersomes sustain free radical polymerization of the hydrophobic butadiene, thereby generating a semipermeable nano-shell. Cross-linked giant vesicles prove stable in chloroform and can also be dehydrated and re-hydrated without rendering the ∼9 nm thick membrane core; the results imply defectfree membranes many microns-squared in area. Surface elastic moduli as well as sustainable wall stresses up to 10 3 Atm, orders of magnitude greater than any natural lipid membrane, appear consistent with strong tethering between close-packed neighbors. The enormous stability of the giant vesicles can be tuned down for application: blending in the hydrogenated analogue poly(ethylene oxide)-polyethylethylene modulates the effective elastic constants as well as the rupture strength by orders of magnitude. The results appear consistent with rigidity percolation through a finite-layer stack of two-dimensional lattices. Moreover, below the percolation limit, a regime of hyper-instability emerges, reflecting perhaps nanoscale demixing and suggestive of the limitations encountered with low reactivity lipids. The results provide general insights into covalent cross-linking within self-assembled nanostructures.

No abstract

One-component homopolymers of cationic monomers (polycations) and diblock copolymers comprising poly(ethylene glycol) (PEG) and a polycation block have been the most widely used types of polymers for formulation of polymer-based gene delivery systems. In this study, we incorporate a hydrophobic middle block into the conventional PEG-polycation architecture, and investigate the effects of this hydrophobic modification on the physicochemical and cell-level biological properties of the polymer-DNA complexes that are relevant to gene delivery applications. The ABC-type triblock copolymer used in this study consists of (A) PEG, (B) hydrophobic poly(n-butyl acrylate) (PnBA) and (C) cationic poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) component polymers. The properties of the triblock copolymer/DNA complexes are compared with those of two other, more conventional DNA carriers derived, respectively, using a PDMAEMA homopolymer and a PEG-PDMAEMA diblock copolymer having comparable molecular weights for individual blocks. The PEG-PnBA-PDMAEMA polymer forms, in aqueous solution, positively-charged spherical micelles. The electrostatic complexation of these micelles with plasmid DNA molecules results in the formation of stable small-size DNA particles coated with a micelle monolayer, as confirmed by agarose gel electrophoresis, dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM). Proton nuclear magnetic resonance (1H NMR) spectroscopy measurements indicate that the whole micelle-DNA assembly (named for convenience as “micelleplex”) is shielded predominantly by the PEG chains. DLS and optical microscopy imaging measurements indicate that in comparison with PDMAEMA/DNA polyplexes, the micelleplexes have a significantly lower tendency to aggregate under physiological salt concentrations, and show reduced interactions with negatively-charged components in serum such as albumin and erythrocytes. While the micelleplexes are comparable with the PEG-PDMAEMA-based DNA polyplexes in terms of their stability against aggregation under high salt concentrations and in the presence of the albumin protein, they have a slightly higher tendency to interact with erythrocytes than the diblock copolymer polyplexes. Agarose gel electrophoresis measurements indicate that relative to the PEG-PDMAEMA polyplexes, the micelleplexes provide better protection of the encapsulated DNA from enzymatic degradation, and also exhibit greater stability against disintegration induced by polyanionic additives; in these respects, the PDMAEMA homopolymer-based polyplexes show the best performance. In vitro studies in HeLa cells indicate that the PDMAEMA polyplexes show the highest gene transfection efficiency among the three different gene delivery systems. Between the micelleplexes and PEG-PDMAEMA polyplexes, a higher gene transfection efficiency is observed with the latter system. All three formulations show comparable levels of cytotoxicity in HeLa cells.

Coronal structures of the micelles spontaneously formed in water by poly(ethylene oxide)-b-polybutadiene (PEO-PB) were investigated using small-angle neutron scattering (SANS). Selective deuterium labeling of the hydrophobic PB block was employed to enhance the neutron scattering contrast between the PEO and PB segments for subsequent structural characterization of their micelles. Analyses of the core-and corona-contrast SANS data based on the intramicellar interference factors led to determination of the segment density profiles of the micellar PEO brushes. Both spherical and cylindrical brushes proved to have coronal layers that are best described in form by a concave concentration profile. The results are consistent with the view that the PEO segments, despite favorable interactions with water molecules, are significantly accumulated near the hydrophobic interface, possibly due to the effect of the strong incompatibility of PB and water.

Recently, many theranostic nanomaterials have been developed by integrating therapeutic and diagnostic agents in a single regimen. Real-time visualization of nano drug carrier biodistributions, drug release processes and therapeutic responses can provide critical information needed for dynamically optimizing treatment operations in a personalized manner in real time. This review highlights recent progresses in the development of multifunctional nanoparticles possessing both therapeutic and imaging functionalities for cancer therapy. The advantages of using nanoparticle platforms are discussed. Examples demonstrating various combinations of imaging and therapeutic modalities are highlighted.