The optical and redox properties of a series of 3,4‐ethylenedioxythiophene oligomers (EDOTn, n=1–4) and their β,β′‐unsubstituted analogues (Tn, n=1–4) are described. Both series are end capped with phenyl groups to prevent irreversible α‐coupling reactions during oxidative doping. Absorption and fluorescence spectra of both series reveal a significantly higher degree of intrachain conformational order in the EDOTn oligomers. Oxidation potentials (EPA1 and EPA2) determined by cyclic voltammetry reveal that those of EDOTn are significantly lower than the corresponding Tn oligomers as a consequence of the electron‐donating 3,4‐ethylenedioxy substitution. Linear fits of EPA1 and EPA2 versus the reciprocal number of double bonds reveal significantly steeper slopes for the EDOTn than for the Tn oligomers. This could indicate a more effective conjugation for the EDOTn series, confirmed by the fact that coalescence of EPA1 and EPA2 is reached already at relatively short chain lengths (≈5 EDOT units) in contrast to the Tn series (>10 thiophene units). The stepwise chemical oxidation of the EDOTn and Tn oligomers in solution was carried out to obtain radical cations and dications. The energies of the optical transitions of the radical cations and dications as determined by UV/Vis/NIR spectroscopy were similar for the two series. These spectroscopic observations are consistent with quantum‐chemical calculations performed on the singly charged molecules. Cooling solutions containing T2.+, T3.+, EDOT2.+, and EDOT3.+ revealed the reversible formation of dimers, albeit with a somewhat different tendency, expressed in the values for the dimerization enthalpy.

Dextran vesicular nanoscaffolds were developed based on polysaccharide and renewable resource alkyl tail for dual encapsulation of hydrophilic and hydrophobic molecules (or drugs) and delivery into cells. The roles of the hydrophobic segments on the molecular self-organization of dextran backbone into vesicles or nanoparticles were investigated in detail. Dextran vesicles were found to be a unique dual carrier in which water-soluble molecules (like Rhodamine-B, Rh-B) and polyaromatic anticancer drug (camptothecin, CPT) were selectively encapsulated in the hydrophilic core and hydrophobic layer, respectively. The dextran vesicles were capable of protecting the plasma-sensitive CPT lactone pharmacophore against the hydrolysis by 10× better than the CPT alone in PBS. The aliphatic ester linkage connecting the hydrophobic tail with dextran was found to be cleaved by esterase under physiological conditions for fast releasing of CPT or Rh-B. Cytotoxicity of the dextran vesicle and its drug conjugate were tested on mouse embryonic fibroblast cells (MEFs) using MTT assay. The dextran vesicular scaffold was found to be nontoxic to living cells. CPT loaded vesicles were found to be 2.5-fold more effective in killing fibroblasts compared to that of CPT alone in PBS. Confocal microscopic images confirmed that both Rh-B and CPT loaded vesicles to be taken up by fibroblasts compared to CPT alone, showing a distinctly perinuclear localization in cells. The custom designed dextran vesicular provides new research opportunities for dual loading and delivering of hydrophilic and hydrophobic drug molecules.

Thiophenebisboronic derivatives (acids and esters) have been successfully utilized for the first time in palladium-catalyzed Suzuki polycondensations to prepare well-defined alternating thiophenephenylene copolymers. 2,5-Thiophenebis(boronic acid) and its corresponding 1,3-propanediol and pinacol diesters have been synthesized and polymerized with 2,5-dialkoxy-1,4-diiodobenzenes in the presence of Pd(OAc) 2 or Pd(PPh3)4 catalysts. SEC analysis showed that the polymers have moderate molecular weight with a polydispersity of 1.2 to 2.4. The role of the boronic derivatives and the catalyst on the yield and molecular weight of the resulting polymers have been investigated in detail. MALDI-TOF mass spectrometry has been used to elucidate the limiting steps in the polymerization and to assess the end groups. The results suggest that hydrolytic deboronation limits the formation of high molecular weight polymers. The polymers prepared using Pd(OAc) 2 possess various end groups and contain macrocycles, whereas Pd(PPh3)4 produces much cleaner polymers. However, the use of Pd(PPh3)4 introduces phenyl end groups via aryl-aryl exchange between the catalytic palladium intermediate and the triphenylphosphine ligand. We found that this aryl-aryl exchange can be suppressed by the introduction of side chain branching in the 2,5-dialkoxy-1,4-diiodobenzene, and as result defect-free, perfectly alternating, chains with mainly thiophene end groups have been obtained in monomodal molecular weight distribution.

We demonstrate here, for the first time, a unique strategy for conducting polyaniline nanofibers based on renewable resources. Naturally available cardanol, which is an industrial waste and main pollutant from the cashew nut industry, is utilized for producing well-defined polyaniline nanofibers. A new amphiphilic molecule is designed and developed from cardanol, which forms a stable emulsion with aniline for a wide composition range in water (1:1 to 1:100 dopant/aniline mole ratio) to produce polyaniline nanofibers. The scanning electron microscopy and transmission electron microscopy analysis of the nanofibers reveals that the dopant/aniline ratio plays a major role in determining the shape and size of polyaniline nanofibers. The nanofiber length increases with the increase in the dopant/aniline ratio, and perfectly linear, well-defined nanofibers of lengths as long as 7-8 muM were produced. The amphiphilic dopant has a built-in head-to-tail geometry and effectively penetrates into the polyaniline chains to form highly organized nanofibers. Wide-angle X-ray diffraction (WXRD) spectra of the nanofibers showed a new peak at 2theta = 6.3 (d spacing = 13.9 A) corresponding to the three-dimensional solid-state ordering of polyaniline-dopant chains, and this peak intensity increases with increase in the nanofiber length. The comparison of morphology and WXRD reveals that high ordering in polyaniline chains results in the formation of long, well-defined nanofibers, and this direct correlation for the polyaniline nanofibers with solid-state ordering has been established. The conductivity of the polyaniline nanofibers also increases with increase in the solid-state ordering rather than increasing with the extent of doping. The polyaniline nanofibers are freely soluble in water and possess high environmental and thermal stability up to 300 degrees C for various applications.

The role of pi-stack induced molecular aggregation on solution and solid-state luminescent properties was investigated for the tricyclodecane substituted bulky (p-phenylenevinylene)s (BTCD-60, with 60% bulky group), oligophenylenevinylenes (MEH-OPV and BTCD-OPV)s, and their polymer-oligomer binary blends. The natures of the solvent, concentration, solvent combinations (good or bad), and temperature were employed as stimuli to probe the origin of the molecular aggregates in bulky conducting polymers. Absorption, photoluminescence (PL), and time-resolved fluorescence spectroscopic techniques were employed as tools to trace aggregation in solvents such as toluene, tetrahydrofuran (THF), THF and methanol, or THF and water as well as in the solid state. The absorbance spectra of poly(2-methoxy-5-(2-ethylhexyloxy))-1,4-phenylenevinylene (MEH-PPV) and BTCD-60 indicated that the films obtained from polymers that were dissolved in aromatic solvents such as toluene were found to possess more pi-stacking as compared to that of films obtained from a good solvent such as THF. The solid-state emission spectrum of BTCD-60 was found to show almost a 5-6 times enhancement in PL intensity as compared to that of MEH-PPV. Concentration dependent excitation spectra of the polymers confirmed the presence of aggregated polymer chains in MEH-PPV, which is the main reason for the quenching of luminescence intensity in the polymer. Solvent induced aggregation studies of polymers in THF and methanol mixture further supports the existence of strong aggregation in MEH-PPV as compared to that of bulky BTCD-60. Variable temperature absorption studies confirmed the reversibility of molecular aggregation on heating/cooling cycles, and the extent of aggregation was found more in MEH-PPV chains as compared to that of BTCD-60. MEH-PPV/OPV binary blends were prepared in the entire composition range from 0 to 100% via solution blending techniques. Through selective PL excitation techniques, the effect of oligomer-to-polymer energy transfer and also luminescent enhancement in MEH-PPV via interchain separation were investigated. Both the energy transfer and the interchain separation were found to be more effective on the enhancement of luminescence properties in the BTCD blends as compared to that of MEH blends. Time-resolved fluorescence studies confirmed the existence of two types of species corresponding to the free and aggregated chains in the polymer matrix with lifetimes in the range of 0.5-2.0 ns. In the present investigation, we have successfully shown that the molecular aggregation of the pi-conjugated polymers, oligomers, and their binary blends can be controlled via suitable bulky substitution to tune their emission properties in solution as well as in the solid state.

Platinum drug delivery against the detoxification of cytoplasmic thiols is urgently required for achieving efficacy in breast cancer treatment that is over expressed by glutathione (GSH, thiol-oligopeptide). GSH-resistant polymer-cisplatin core-shell nanoparticles were custom designed based on biodegradable carboxylic functional polycaprolactone (PCL)-block-poly(ethylene glycol) diblock copolymers. The core of the nanoparticle was fixed as 100 carboxylic units and the shell part was varied using various molecular weight poly(ethylene glycol) monomethyl ethers (MW of PEGs = 100-5000 g mol(-1)) as initiator in the ring-opening polymerization. The complexation of cisplatin aquo species with the diblocks produced core-shell nanoparticles of 75 nm core with precise size control the particles up to 190 nm. The core-shell nanoparticles were found to be stable in saline solution and PBS and they exhibited enhanced stability with increase in the PEG shell thickness at the periphery. The hydrophobic PCL layer on the periphery of the cisplatin core behaved as a protecting layer against the cytoplasmic thiol residues (GSH and cysteine) and exhibited <5% of drug detoxification. In vitro drug-release studies revealed that the core-shell nanoparticles were ruptured upon exposure to lysosomal enzymes like esterase at the intracellular compartments. Cytotoxicity studies were performed both in normal wild-type mouse embryonic fibroblast cells (Wt-MEFs), and breast cancer (MCF-7) and cervical cancer (HeLa) cell lines. Free cisplatin and polymer drug core-shell nanoparticles showed similar cytotoxicity effects in the HeLa cells. In MCF-7 cells, the free cisplatin drug exhibited 50% cell death whereas complete cell death (100%) was accomplished by the polymer-cisplatin core-shell nanoparticles. Confocal microscopic images confirmed that the core-shell nanoparticles were taken up by the MCF-7 and HeLa cells and they were accumulated both at the cytoplasm as well at peri-nuclear environments. The present investigation lays a new foundation for the polymer-based core-shell nanoparticles approach for overcoming detoxification in platinum drugs for the treatment of GSH over-expressed breast cancer cells.

The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 ± 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX·HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL(-1) in PBS. MTT assays on fibroblast cells revealed that DOX·HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells.

Multi-drug delivery based on polymer nano-scaffolds is an essential protocol to be developed for better administration of anticancer drugs to enhance their therapeutic efficacies against cancer cells. Here, we report dual delivery polysaccharide nano-vesicles that are capable of loading and delivering both water soluble and water insoluble drugs together in a single polymer scaffold. The selective rupture of the nano-vesicular assembly under intracellular enzyme conditions allowed the simultaneous delivery of a hydrophobic drug camptothecin (CPT) and hydrophilic drug doxorubicin (DOX) supporting their synergistic killing of breast and colon cancer cells. The polysaccharide nano-vesicles have allowed us to address a few important questions regarding the need for multiple drug administration in cancer cells including (a) the role of simultaneous drug release, (b) antagonistic versus synergistic effects of drug combinations and (c) how these are affected by the ratio of drugs. Further, evaluation of the role of caveolae in endocytosis of these polymer scaffolds was also made. The vesicular scaffolds were found to preserve and deliver DOX resulting in 50-60% better killing of cancer cells than the free drug. Additionally, dual loaded nano-vesicles when compared to drug cocktails with individual drugs in separate nano-vesicles (at comparable molar ratios) suggest the relative drug concentration following release and mode of delivery to be both important in cancer cell killing. Results from these experiments have revealed newly developed polysaccharide nano-vesicles loaded with DOX and CPT drugs as potential candidates for improved breast cancer cell killing. Thus, these custom-designed polysaccharide nano-vesicles provide a new perspective on multi-anticancer drug delivery systems and their efficacy.