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Abstract: It is well-known that the Dengue fever virus undergoes a distinct morphological transition from topologically smooth particles to ‘bumpy’ particle on increasing the temperature from that of the mosquito carrier (28 °C) to that of the human host (37 °C). This virus also possesses pH-sensitive surface domains that undergo conformational changes during infection which facilitates exit from the endosomes. Herein we take a bio-inspired approach to design synthetic Dengue virus-mimicking nanoparticles to target triple-negative (TN) breast cancer cells that overexpress SR-B1 scavenger receptors. Thus, sterile pH-responsive methacrylic ABC triblock copolymer vesicles were prepared in aqueous solution via polymerization-induced self-assembly. Microphase separation between two enthalpically-incompatible hydrophobic membrane-forming blocks produced a well-defined framboidal morphology, with surface globules of ∼28 nm diameter protruding from the membrane. The hydrophilic stabilizer block comprises 97% hydroxyl-functionalized chains and 3% phosphorylcholine-functionalized chains, with the latter being critical for selective intracellular uptake. These framboidal vesicles remain intact at neutral pH but become swollen and cationic at pH 5–6 because the tertiary amine residues in the hydrophobic C block become protonated. We demonstrate that such nanoparticles enable selective targeting of TN breast cancer cells. This is because such malignant cells overexpress SR-B1 receptors for naturally-occurring phospholipids and hence take up the phosphorylcholine-decorated framboidal vesicles preferentially. In contrast, negligible cell uptake is observed over the same time period for both human dermal fibroblasts and normal breast cancer cells that minimally express the SR-B1 receptor. Moreover, we show that genetic material within such pH-responsive framboidal vesicles can be efficiently delivered to the cell nuclei while maintaining high cell viability.

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Abstract: This work focuses on the use of copolymer nanoparticles as a dispersant for a model pigment (silica). Reversible addition-fragmentation chain transfer (RAFT) alcoholic dispersion polymerization was used to synthesize sterically stabilized diblock copolymer nanoparticles. The steric stabilizer block was poly(2-dimethylamino)ethyl methacrylate) [PDMA] while the core-forming block was poly(benzyl methacrylate) [PBzMA]. The mean degrees of polymerization for the PDMA and PBzMA blocks were 71 and 100, respectively. TEM studies confirmed a near-monodisperse spherical morphology, while DLS studies indicated an intensity-average diameter of 30 nm. Small angle X-ray scattering (SAXS) reported a volume-average diameter of 29 ± 0.9 nm and a mean aggregation number of 154. Aqueous electrophoresis measurements confirmed that these PDMA71-PBzMA100 nanoparticles acquired cationic character when transferred from ethanol to water as a result of protonation of the weakly basic PDMA chains. Electrostatic adsorption of these nanoparticles from aqueous solution onto 470 nm silica particles led to either flocculation at submonolayer coverage or steric stabilization at or above monolayer coverage, as judged by DLS. This technique indicated that monolayer coverage was achieved on addition of approximately 465 copolymer nanoparticles per silica particle, which corresponds to a fractional surface coverage of around 0.42. These adsorption data were corroborated using thermogravimetry and UV spectroscopy. TEM studies indicated that the cationic nanoparticles remained intact at the silica surface after electrostatic adsorption, while aqueous electrophoresis confirmed that surface charge reversal occurred below pH 7. The relatively thick layer of adsorbed nanoparticles led to a significant reduction in the effective particle density of the silica particles from 1.99 g cm-3 to approximately 1.74 g cm-3, as judged by disk centrifuge photosedimentometry (DCP). Combining the DCP and SAXS data suggests that essentially no deformation of the PBzMA cores occurs during nanoparticle adsorption onto the silica particles.

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Abstract: A series of model sterically stabilized diblock copolymer nanoparticles has been designed to aid the development of analytical protocols in order to determine two key parameters: the effective particle density and the steric stabilizer layer thickness. The former parameter is essential for high resolution particle size analysis based on analytical (ultra)centrifugation techniques (e.g., disk centrifuge photosedimentometry, DCP), whereas the latter parameter is of fundamental importance in determining the effectiveness of steric stabilization as a colloid stability mechanism. The diblock copolymer nanoparticles were prepared via polymerization-induced self-assembly (PISA) using RAFT aqueous emulsion polymerization: this approach affords relatively narrow particle size distributions and enables the mean particle diameter and the stabilizer layer thickness to be adjusted independently via systematic variation of the mean degree of polymerization of the hydrophobic and hydrophilic blocks, respectively. The hydrophobic core-forming block was poly(2,2,2-trifluoroethyl methacrylate) [PTFEMA], which was selected for its relatively high density. The hydrophilic stabilizer block was poly(glycerol monomethacrylate) [PGMA], which is a well-known non-ionic polymer that remains water-soluble over a wide range of temperatures. Four series of PGMAx–PTFEMAy nanoparticles were prepared (x = 28, 43, 63, and 98, y = 100–1400) and characterized via transmission electron microscopy (TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). It was found that the degree of polymerization of both the PGMA stabilizer and core-forming PTFEMA had a strong influence on the mean particle diameter, which ranged from 20 to 250 nm. Furthermore, SAXS was used to determine radii of gyration of 1.46 to 2.69 nm for the solvated PGMA stabilizer blocks. Thus, the mean effective density of these sterically stabilized particles was calculated and determined to lie between 1.19 g cm–3 for the smaller particles and 1.41 g cm–3 for the larger particles; these values are significantly lower than the solid-state density of PTFEMA (1.47 g cm–3). Since analytical centrifugation requires the density difference between the particles and the aqueous phase, determining the effective particle density is clearly vital for obtaining reliable particle size distributions. Furthermore, selected DCP data were recalculated by taking into account the inherent density distribution superimposed on the particle size distribution. Consequently, the true particle size distributions were found to be somewhat narrower than those calculated using an erroneous single density value, with smaller particles being particularly sensitive to this artifact.

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Abstract: A poly(2-(dimethylamino)ethyl methacrylate) (PDMA) chain transfer agent (CTA) is used for the reversible addition–fragmentation chain transfer (RAFT) alcoholic dispersion polymerization of benzyl methacrylate (BzMA) in ethanol at 70 °C. THF GPC analysis indicated a well-controlled polymerization with molecular weight increasing linearly with conversion. GPC traces also showed high blocking efficiency with no homopolymer contamination apparent and Mw/Mn values below 1.35 in all cases. 1H NMR studies confirmed greater than 98% BzMA conversion for a target PBzMA degree of polymerization (DP) of up to 600. The PBzMA block becomes insoluble as it grows, leading to the in situ formation of sterically stabilized diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA). Fixing the mean DP of the PDMA stabilizer block at 94 units and systematically varying the DP of the PBzMA block enabled a series of spherical nanoparticles of tunable diameter to be obtained. These nanoparticles were characterized by TEM, DLS, MALLS, and SAXS, with mean diameters ranging from 35 to 100 nm. The latter technique was particularly informative: data fits to a spherical micelle model enabled calculation of the core diameter, surface area occupied per copolymer chain, and the mean aggregation number (Nagg). The scaling exponent derived from a double-logarithmic plot of core diameter vs PBzMA DP suggests that the conformation of the PBzMA chains is intermediate between the collapsed and fully extended state. This is in good agreement with 1H NMR studies, which suggest that only 5−13% of the BzMA residues of the core-forming chains are solvated. The Nagg values calculated from SAXS and MALLS are in good agreement and scale approximately linearly with PBzMA DP. This suggests that spherical micelles grow in size not only as a result of the increase in copolymer molecular weight during the PISA synthesis but also by exchange of individual copolymer chains between micelles and/or by sphere–sphere fusion events.

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Abstract: Soot formation in diesel engines is known to cause premature engine wear. Unfortunately, genuine diesel soot is expensive to generate, so carbon blacks are often used as diesel soot mimics. Herein, the suitability of a commercial carbon black (Regal 250R) as a surrogate for diesel soot dispersed in engine base oil is examined in the presence of two commonly used polymeric lubricant additives. The particle size, morphology, and surface composition of both substrates are assessed using BET surface area analysis, TEM, and XPS. The extent of adsorption of a poly(ethylene-co-propylene) (dOCP) statistical copolymer or a polystyrene-block-poly(ethylene-co-propylene) (PS−PEP) diblock copolymer onto carbon black or diesel soot from n-dodecane s compared indirectly using a supernatant depletion assay technique via UV spectroscopy. Thermogravimetric analysis is also used to directly determine the extent of copolymer adsorption. Degrees of dispersion are examined using optical microscopy, TEM, and analytical centrifugati n. SAXS studies reveal some structural differences between carbon black and diesel soot particles. The mean radius of gyration determined for the latter is significantly smaller than that calculated for the former, and in the absence of any copolymer, diesel soot suspended in n-dodecane forms relatively loose mass fractals compared to carbon black. SAXS provides evidence for copolymer adsorption and indicates that addition of either copolymer transforms the initially compact agglomerates into relatively loose aggregates. Addition of dOCP or PS−PEP does not significantly affect the structure of the carbon black primary particles, with similar results being observed for diesel soot. In favorable cases, remarkably similar data can be obtained for carbon black and diesel soot when using dOCP and PS−PEP as copolymer dispersants. However, it is not difficult to identify simple copolymer−particle−solvent combinations for which substantial differences can be observed. Such observations are most likely the result of issimilar surface chemistries, which can profoundly affect the colloidal stability.