This article reviews the analytical tool chest used for characterizing alkoxylates and their associated copolymer mixtures. Specific emphasis will be placed upon the use of mass spectrometry-based techniques as rapid characterization tools for optimizing reaction processes in an industrial R&D setting. An initial tutorial will cover the use of matrix-assisted laser desorption/ionization-mass spectrometry and tandem mass spectrometry fragmentation for detailed component analysis (e.g., polyol and isocyanate) of a model polyurethane-based foam. Next, this critical feedback information will be used with the guidance of mass spectrometry to initiate the development of a new, more efficient, tris(pentafluorophenyl)borane (FAB) catalyst-based alkoxylation process for generating the next generation of glycerin-initiated poly(propylene oxide)-co-poly(ethylene oxide) copolymers. Examples will be provided for each step in the FAB-based optimization process that were required to generate the final product. Following this example, two-dimensional liquid chromatography, supercritical fluid chromatography, and ion mobility separations, along with their coupling to mass spectrometry, will be reviewed for their efficiency in characterizing and quantitating the components within these complex polyether polyol mixtures.

Recent advances in the controlled RAFT polymerization of complex macromolecular architectures based on poly(N-vinyl pyrrolidone), PNVP, are summarized in this review article. Special interest is given to the synthesis of statistical copolymers, block copolymers, and star polymers and copolymers, along with graft copolymers and more complex architectures. In all cases, PNVP is produced via RAFT techniques, whereas other polymerization methods can be employed in combination with RAFT to provide the desired final products. The advantages and limitations of the synthetic methodologies are discussed in detail.

The influence of the macromolecular architecture of block copolymers containing poly(N,N-dimethyl acrylamide) (PDMA) on the optical characteristics and sensing properties of corresponding thin films is discussed. Series of hydrophilic PDMA-based copolymers of different chemical composition and chain architecture such as triblock, star-shaped, and branched were synthesized. The copolymers were characterized using conventional spectroscopic techniques as well as methods for characterization of copolymer macromolecular characteristics in solution, namely size-exclusion chromatography and static light scattering. Thin films of the copolymers of nanometer scale thickness were deposited on silicon substrates by the spin-coating method. The refractive index and extinction coefficient of the copolymer films were calculated from the reflectance spectra by using non-linear curve fitting methods and the composition-structure-optical properties relationships were evaluated. Humidity-sensing properties of the films were studied by measuring reflectance spectra of the films at a relative humidity range from 5 to 95%RH. The implementation of the copolymer films as optical sensors of humidity is justified and discussed.

In recent years, substantial advances have been achieved in the design and synthesis of nonviral gene vectors. However, lack of effective and biocompatible vectors still remains a major challenge that hinders their application in clinical settings. In the past decade, there has been a rapid expansion of cationic antimicrobial polymers, due to their potent, rapid, and broad-spectrum biocidal activity against resistant microbes, and biocompatible features. Given that antimicrobial polymers share common features with nonviral gene vectors in various aspects, such as membrane affinity, functional groups, physicochemical characteristics, and unique macromolecular architectures, these polymers may provide us with inspirations to overcome challenges in the design of novel vectors toward more safe and efficient gene delivery in clinic. Building off these observations, we provide here an overview of the structure-function relationships of polymers for both antimicrobial applications and gene delivery by elaborating some key structural parameters, including functional groups, charge density, hydrophobic/hydrophilic balance, MW, and macromolecular architectures. By borrowing a leaf from antimicrobial agents, great advancement in the development of newer nonviral gene vectors with high transfection efficiency and biocompatibility will be more promising. STATEMENT OF SIGNIFICANCE: The development of gene delivery is still in the preclinical stage for the lack of effective and biocompatible vectors. Given that antimicrobial polymers share common features with gene vectors in various aspects, such as membrane affinity, functional groups, physicochemical characteristics, and unique macromolecular architectures, these polymers may provide us with inspirations to overcome challenges in the design of novel vectors toward more safe and efficient gene delivery in clinic. In this review, we systematically summarized the structure-function relationships of antimicrobial polymers and gene vectors, with which the design of more advanced nonviral gene vectors is anticipated to be further boosted in the future.

The impact of the molecular architecture on the transfection efficiency of PEGylated poly(amino acid) block copolymers was investigated for PEG-b-p(l-Lys)x -b-p(l-Leu)y , PEG-b-p(l-Leu)x -b-p(l-Lys)y , and PEG-b-p((l-Leu)x -co-(l-Lys)y ). The block lengths of p(l-Lys) and p(l-Leu) were varied between 10, 20, and 40; and 10 and 20, respectively, to study the influence of the ionic/hydrophobic balance. The results show that ABC triblock copolymers form smaller and more stable polyplexes with plasmid DNA than AB diblock copolymers-as verified by long-term aggregation and ethidium bromide exclusion studies-protect the DNA more effectively against nucleases, and provide better transfection efficiencies, as indicated by total protein as well as luciferase expression. More detailed studies revealed that triblock copolymers with p(l-Leu) forming the C-block were most efficient in DNA complexation with a 2.3 times higher transfection rate. Furthermore, increasing the cationic character by increasing the p(l-Lys) chain length led to up to 25% higher transfection but at the same time induced some cytotoxicity. Diblock copolymers, where the amino acid-building blocks exist as a random copolymer, bind more loosely with DNA leading to less compact and less stable aggregates with lower transfection efficiencies.

This work reports the molecular design, synthesis, and systematic study on the bulk self-assembly behaviors of three series of polyhedral oligomeric silsesquioxane (POSS)-based multiheaded giant surfactants XDPOSS-PSn (X = 2, 3, and 4), which are composed of two, three, or four hydrophilic hydroxyl-group-functionalized DPOSS cages attached via one junction point to a hydrophobic polystyrene (PS) chain. These series of hybrid polymeric amphiphiles with precisely defined chemical structure and controllable molecular architecture are synthesized by the sequential usage of \"click\" reactions. By tuning molecular weights of the PS tail, we established full phase diagrams of XDPOSS-PSn as a function of the volume fractions of PS chains (VfPS). We found that the self-assembled structures were greatly influenced by the molecular architecture. Strikingly, our results showed that the lamellar morphology, which usually existed at relatively symmetric compositions in common diblock copolymers, became the thermodynamically stable phase in the 3DPOSS-PSn and 4DPOSS-PSn samples even at an asymmetric composition up to VfPS = 0.842, with the ratio between the thicknesses of PS and DPOSS lamellae up to 5.32. This unusual phenomenon induced by molecular architectural variation could be explained by the large cross-sectional area of DPOSS cages at the nanophase-separated domain interface and high elastic deformation energy of clustered DPOSS cages which have relatively rigid conformation. The unique bulk self-assembly behaviors in our POSS-based multiheaded giant surfactants provide insights in developing hybrid nanomaterials toward unconventional nanostructures.

The linear, Y-shaped, and linear-dendritic block copolymers of methoxy poly(ethylene glycol)-block-polyamidoamine-block-poly(l-glutamic acid) (MPEG-b-PAMAM-b-PGA) with one, two, four, and eight PGA arms but similar MPEG/PGA weight ratios (W/W) (named as P1PA, P2PA, P4PA and P8PA, respectively) were synthesized and comparatively investigated for doxorubicin hydrochloride (DOX) delivery. All the obtained block copolymers were highly biocompatible and could efficiently load DOX into nanoparticles (NPs) through electrostatic interaction. The NPs formed by linear (P1PA) or Y-shaped (P2PA) block copolymers and DOX were spherically shaped with smaller sizes, while the NPs formed from linear-dendritic block copolymers (P4PA and P8PA) were irregular in shape and larger in size. The P1PA/DOX and P2PA/DOX NPs exhibited better DOX protection and slower DOX release profile. However, cell cytotoxicity assays indicated that all the DOX-loaded NPs exhibited similar cytotoxicities with free DOX, indicating effective DOX release after cellular uptake. The NPs from linear and Y-shaped block copolymers greatly extended the blood circulation time, and displayed more accumulation in tumor site and less accumulation in the liver and kidney compared with the linear-dendritic counterparts. In addition, the P1PA/DOX and P2PA/DOX NPs also exhibited higher anti-tumor efficacy and less toxicity than the other DOX formulations. All these results indicated that the linear and Y-shaped MPEG-b-PAMAM-b-PGA block copolymers displayed better DOX delivery ability in anti-tumor treatment than the linear-dendritic copolymers.
Polymeric NPs derived from block copolymers have emerged as effective vehicles for drug delivery. However, the majority of the researches in this field have involved simple linear block copolymers and there are very few comparative studies on the self-assembly, in vitro, and in vivo drug delivery by the block copolymers with similar composition but different architectures. In this study, a series of linear, Y-shaped, and linear-dendritic polypeptide-based block copolymers were prepared and thoroughly investigated for DOX delivery. These block polymers loaded DOX into NPs with different sizes and morphologies, and exhibited different anti-tumor capabilities both in vitro and in vivo. The results indicated that the architecture of the block copolymers played an important role in their drug delivery behaviors.

In skeletal muscle, Ca(2+) release from sarcoplasmic reticulum (SR) following the action potential relies on the delicate architecture of the T-Tubule/SR junction. The T-Tubule/SR junction comprises two membrane systems: the integral proteins DHPR and RyR1 and the Ca(2+)-buffering apparatus within the SR lumen. The arrangement and interactions of the components have remained elusive due to technological limitations. Here, we determined whether electron tomography is effective fort the in situ determination of the relationships between RyR1 and DHPR, the SR membrane and other involved structures. First, we visually confirmed that RyR1 and DHPR are close neighbors that are mutually staggered with each other and directly interact with one of RyR1 subunits. Second, the Ca(2+) storage network within the SR lumen is directly correlated with RyR1. These results suggest that the excitation of the T-Tubule may induce Ca(2+) release through a direct interaction among DHPR, RyR1 and the Ca(2+) buffering apparatus. These results indicate that electron tomography has potential as an efficient method for the in situ characterization of the complex architecture and arrangement of two integral-integral-membrane proteins in the context of the surrounding phospholipid-bilayer and proteins.

In this work, we explore the ability of utilizing hydrogels synthesized from a temperature-sensitive polymer and a polyelectrolyte to desalinate salt water by means of reversible thermally induced absorption and desorption. Thus, the influence of the macromolecular architecture on the swelling/deswelling behavior for such hydrogels was investigated by tailor-made network structures. To this end, a series of chemically cross-linked polymeric hydrogels were synthesized via free radical-initiated copolymerization of sodium acrylate (SA) with the thermoresponsive comonomer N-isopropylacrylamide (NIPAAm) by realizing different structural types. In particular, two different polyNIPAAm macromonomers, either with one acrylate function at the chain end or with additional acrylate functions as side groups were synthesized by controlled polymerization and subsequent polymer-analogous reaction and then used as building blocks. The rheological behaviors of hydrogels and their estimated mesh sizes are discussed. The performance of the hydrogels in terms of swelling and deswelling in both deionized water (DI) and brackish water (2 g/L NaCl) was measured as a function of cross-linking degree and particle size. The salt content could be reduced by 23% in one cycle by using the best performing material.

Certain natural products such as gambogic acid (GA) exhibit potent antitumor effects. Unfortunately, administration of these natural products is limited by their poor solubility in conventional pharmaceutical solvents. In this study, a series of telodendrimers, composed of linear polyethylene glycol (PEG)-blocking-dendritic oligomer of cholic acid (CA) and vitamin E (VE), have been designed with architectures optimized for efficient delivery of GA and other natural anticancer compounds. Two of the telodendrimers with segregated CA and VE domains self-assembled into stable cylindrical and/or spherical nanoparticles (NPs) after being loaded with GA as observed under transmission electron microscopy (TEM), which correlated with the dynamic light scattering (DLS) analysis of sub-30 nm particle sizes. A very high GA loading capacity (3:10 drug/polymer w/w) and sustained drug release were achieved with the optimized telodendrimers. These novel nanoformulations of GA were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug. Near-infrared fluorescence small animal imaging revealed preferential accumulation of GA-loaded NPs into tumor tissue. The optimized nanoformulation of GA achieved superior antitumor efficacy compared to GA-Cremophor EL formulation at equivalent doses in HT-29 human colon cancer xenograft mouse models. Given the mild adverse effects associated with this natural compound and the enhanced anticancer effects via tumor targeted telodendrimer delivery, the optimized GA nanoformulation is a promising alternative to the traditional chemotherapy in colon cancer treatment.