Cellular- and Subcellular-Targeted Delivery Using a Simple All-in-One Polymeric Nanoassembly

Nanocarrier-mediated drug delivery is a promising strategy to maximize the power of chemotherapy and minimize side effects. However, current approaches show insufficient drug-loading capacity and inefficient drug release, and require complex modification processes. Attempts to enhance one of these features often compromise other merits. We describe here a block copolymer assembly system that combines desirable characteristics. The design of self-immolative and crosslinkable hydrophobic moieties offer stable and high encapsulation. Redox-triggerable polymer self-immolation promotes drug release by switching the hydrophobic core into completely hydrophilic chains. The reactive amine handles, presented on their surface, allow “plug to direct” modification with targeting ligands. Functionalized nanoassemblies have been programmed to target specific subcellular compartments. The simplicity, versatility, and efficacy of the system open up possibilities for an all-in-one delivery system.     

Comparison of facially amphiphilic biaryl dendrimers with classical amphiphilic ones using protein surface recognition as the tool

Facially amphiphilic biaryl dendrimers are compared with the more classical benzyl ether amphiphilic dendrimers for molecular recognition, using protein binding as the probe. The protein used for the proposed study is chymotrypsin (ChT). A generation-dependent binding affinity was observed with the benzyl ether dendrimers, while the affinities were independent of generation in the case of the biaryl dendrimers. Similarly, although the ligands incorporated in both dendrons are the same, the biaryl dendrimers are able to bind more proteins compared to the benzyl ether dendrimers. For example, G3-dendron of biaryl dendrimer can bind six molecules of chymotrypsin, whereas G3-analogue of benzyl ether dendrimers can bind only three molecules of chymotrypsin. This result is consistent with our hypothesis that the internal layers of the facially amphiphilic biaryl dendrons are solvent-exposed and accessible for recognition. In addition, the systematic size differences in dendrons were also used to gain insights into the substrate selectivity that the enzyme gains upon binding to a ligand scaffold.     

Structural,optical, and electrical properties of electron beam evaporated CdSe thin films

CdSe films have been deposited on glass substrates at different substrate temperatures between room temperature and 300 °C. The films exhibited hexagonal structure with preferential orientation in the (002) direction. The crystallinity improved and the grain size increased with temperature. Band gap values are found decreasing from about 1.92 eV to 1.77 eV with increase of the substrate temperature. It is observed that the resistivity decreases continuously with temperature. Laser Raman studies show the presence of 2 LO and 3 LO peaks at 416 cm^‐1 and 625 cm^‐1respectively. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Energy and charge transfer dynamics in fully decorated benzyl ether dendrimers and their disubstituted analogues

We examine the photophysics of a series of molecules consisting of a benzthiadiazole core surrounded by a network of benzyl ether arms terminated by aminopyrene chromophores, which function as both energy and electron donors. Three classes of molecules are studied: dendrimers whose peripheries are fully decorated with aminopyrene donors (F), disubstituted dendrimers whose peripheries contain only two donors (D), and linear analogues in which a pair of benzyl ether arms link two donors to the central core (L). The electronic energy transfer (EET) and charge transfer (CT) rates are determined by fluorescence lifetime measurements on the energy donors and electron acceptors, respectively. In all three types of molecules, the EET time scales as the square root of the generation number G, consistent with the flexible nature of the benzyl ether framework. Transient anisotropy measurements confirm that donor-donor energy hopping does not play a major role in determining the EET times. The CT dynamics occur on the nanosecond time scale and lead to stretched exponential decays, probably due to conformational disorder. Measurements at 100 degrees C confirm that conformational fluctuations play a role in the CT dynamics. The average CT time increases with G in the L and D molecules but decreases for the F dendrimers. This divergent behavior as G increases is attributed to the competing effects of larger donor-acceptor distances (which lengthen the CT time) versus a larger number of donors (which shorten the average CT time). This work illustrates two important points about light-harvesting and charge-separation dendrimers. First, the use of a flexible dendrimer framework can lead to a more favorable scaling of the EET time (and thus the light-harvesting efficiency) with dendrimer size, relative to what would be expected for a fully extended dendrimer. Second, fully decorated dendrimers can compensate for the distance-dependent slowdown in CT rate as G increases by providing additional pathways for the CT reaction to occur.     

In Situ Formation of Polymeric Nanoassemblies Using an Efficient Reversible Click Reaction

Polymer–drug conjugates are promising as strategies for drug delivery, because of their high drug loading capacity and low premature release profile. However, the preparation of these conjugates is often tedious. In this paper, we report an efficient method for polymer–drug conjugates using an ultrafast and reversible click reaction in a post‐polymerization functionalization strategy. The reaction is based on the rapid condensation of boronic acid functionalities with salicylhydroxamates. The polymer, bearing the latter functionality, has been designed such that the reaction with boronic acid bearing drugs induces an in situ self‐assembly of the conjugates to form well‐defined nanostructures. We show that this method is not only applicable for molecules with an intrinsic boronic acid group, but also for the other molecules that can be linked to aryl boronic acids through a self‐immolative linker. The linker has been designed to cause traceless release of the attached drug molecules, the efficiency of which has been demonstrated through intracellular delivery.     

Proton conduction in 1H‐1,2,3‐triazole polymers: Imidazole‐like or pyrazole‐like?

Proton transport (PT) plays an important role in many biological processes as well as in materials for renewable energy devices. Gaining insights into functional group requirements for PT would aid the design of new materials that provide enhanced proton conduction. In this report, we outline our efforts to understand the most probable proton conduction pathway in 1H‐1,2,3‐triazole systems. In triazole‐based systems, both imidazole‐ and pyrazole‐like pathways are possible. By systematically comparing structurally analogous polymers based on N‐heterocycles and benz‐N‐heterocycles, we find that the imidazole‐like pathway makes a significant contribution to the proton transfer in 1H‐1,2,3‐triazole systems, while the contribution from pyrazole‐like pathway is negligible. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1851–1858, 2010     

Temperature sensitivity trends and multi-stimuli sensitive behavior in amphiphilic oligomers

A series of oligomers, containing oligo(ethylene glycol) (OEG) moieties, with the same composition of amphiphilic functionalities has been designed, synthesized, and characterized on the basis of their temperature-sensitive behavior. The non-covalent amphiphilic aggregates, formed from these molecules, influence their temperature sensitivity. Covalent tethering of the amphiphilic units also has a significant influence on their temperature sensitivity. The lower critical solution temperatures of these oligomers show increasingly sharp transitions with increasing numbers of OEG functional groups, indicating enhanced cooperativity in dehydration of the OEG moieties when they are covalently tethered. These molecules were also engineered to be concurrently sensitive to enzymatic reaction and pH. This possibility was investigated using porcine liver esterase as the enzyme; we show that enzymatic action on the pentamer lowers its temperature sensitivity. The product moiety from the enzymatic reaction also gives the amphiphilic oligomer a pH-dependent temperature sensitivity.     

Homopolymer micelles in heterogeneous solvent mixtures

Amphiphilic homopolymers containing a hydrophilic and a hydrophobic functionality in each monomer unit have been shown to form polar or apolar containers depending on the solvent environment. When presented with a mixture of solvents, these polymeric containers are capable of releasing certain guest molecules. The fundamental mechanism behind these properties is investigated, and the utility of these assemblies in separations has been demonstrated with an example.     

Using meta conjugation to enhance charge separation versus charge recombination in phenylacetylene donor-bridge-acceptor complexes

A pair of donor-bridge-acceptor electron-transfer complexes, with a carbazole donor and a naphthalimide acceptor connected by either a para- or meta-conjugated phenylacetylene bridge, are synthesized and studied using time-resolved and steady-state spectroscopy. These experiments show that the charge separation times, which depend on the coupling of the donor and acceptor through the excited bridge moiety, are similar for the two molecules (Meta and Para). The charge recombination time, however, is a factor of 10 slower for Meta than for Para. These results are related to changes in the electronic coupling of the bridge depending on its electronic state, and show that meta-conjugated bridges provide a possible motif for the design of asymmetric molecular wires.