Efficient, Solvent-Free, Multicomponent Method for Organic-Base-Catalyzed Synthesis of β‑Phosphonomalonates

An efficient, one-pot, di-<i>n</i>-butylamine-catalyzed, three-component synthesis of β-phosphonomalonates has been developed. A wide range of substrates, including aromatic and fused aromatic aldehydes, were condensed with enolizable C–H activated compounds and dialkylphosphites to give the desired products in excellent yields. This method provides an eco-friendly alternative approach to rapid construction of a diversity-oriented library of β-phosphonomalonates

Easy Synthesis of Hierarchical Carbon Spheres with Superior Capacitive Performance in Supercapacitors

An easy template-free approach to the fabrication of pure carbon microspheres has been achieved via direct pyrolysis of as-prepared polyaromatic hydrocarbons including polynaphthalene and polypyrene. The polyaromatics were synthesized from aromatic hydrocarbons (AHCs) using anhydrous zinc chloride as the Friedel–Crafts catalyst and chloromethyl methyl ether as a cross-linker. The experimental results show that the methylene bridges between phenyl rings generate a hierarchical porous polyaromatic precursor to form three-dimensionally (3D) interconnected micro-, meso-, and macroporous networks during carbonization. These hierarchical porous carbon aggregates of spherical carbon spheres exhibit faster ion transport/diffusion behavior and increased surface area usage in electric double-layer capacitors. Furthermore, micropores are present in the 3D interconnected network inside the cross-linked AHC-based carbon microspheres, thus imparting an exceptionally large, electrochemically accessible surface area for charge accumulation

Fabrication of Microspheres via Solvent Volatization Induced Aggregation of Self-Assembled Nanomicellar Structures and Their Use as a pH-Dependent Drug Release System

A series of oleamide derivatives, (C₁₈H₃₄NO)₂(CH₂)_<i>n</i> [<i>n</i> = 2 (<b>1a</b>), 3 (<b>1b</b>), 4 (<b>1c</b>), or 6 (<b>1d</b>); C₁₈H₃₄NO = oleic amide fragment] and (C₁₈H₃₄NO)­(CH₂)₆NH₂ (<b>2</b>), have been synthesized and their self-assembly is investigated in ethanol/water media. Self-assembly of <b>1a</b> and <b>1b</b> in ethanol/water (1/0.1 <i>v</i>/<i>v</i>) solution (5 mg mL^–1) yields microspheres (MSs) with the average diameter ∼10 μm via a gradual temperature reduction and solvent volatilization process. Under the same self-assembly conditions, microrods (average diameter ∼6 μm and several tens of micrometers in length), micronecklace-like, and shape-irregular microparticles are formed from the self-assembly of <b>1c</b>, <b>1d</b>, and <b>2</b>, respectively. The kinetics of evolution for their self-assemblies by dynamic light scattering technique and in situ observation by optical microscopy reveals that the microstructures formation is from a well-behaved aggregation of nanoscale micelles induced by solvent volatilization. The FT–IR and temperature–dependent ¹H–NMR spectra demonstrate the hydrogen bonding force and π–π stacking, which drove the self-assembly of all oleamide derivatives in ethanol/water. Among the fabricated microstructures, the MSs from <b>1a</b> exhibit the best dispersity, which thus have been used as a scaffold for the in vitro release of doxorubicin. The results demonstrate a pH-sensitive release process, enhanced release specifically at low pH 5.2

Dual Stimuli-Responsive Poly(<i>N</i>‑isopropylacrylamide)‑<i>b</i>‑​poly(l‑histidine) Chimeric Materials for the Controlled Delivery of Doxorubicin into Liver Carcinoma

A series of dual stimuli responsive synthetic polymer bioconjugate chimeric materials, poly­(<i>N</i>-isopropylacrylamide)₅₅-<i>block</i>-poly­(l-histidine)_<i>n</i> [p­(NIPAM)₅₅-<i>b</i>-p­(His)_<i>n</i>] (<i>n</i> = 50, 75, 100, 125), have been synthesized by employing reversible addition–fragmentation chain transfer polymerization of NIPAM, followed by ring–opening polymerization of α-amino acid <i>N</i>-carboxyanhydrides. The dual stimuli responsive properties of the resulting biocompatiable and membrenolytic p­(NIPAM)₅₅-<i>b</i>-p­(His)_<i>n</i> polymers are investigated for their use as a stimuli responsive drug carrier for tumor targeting. Highly uniform self-assembled micelles (∼55 nm) fabricated by p­(NIPAM)₅₅-<i>b</i>-p­(His)_<i>n</i> polymers display sharp thermal and pH responses in aqueous media. An anticancer drug, doxorubicin (Dox), is effectively encapsulated in the micelles and the controlled Dox release is investigated in different temperature and pH conditions. Antitumor effect of the released Dox is also assessed using the HepG2 human hepatocellular carcinoma cell lines. Dox molecules released from the [p­(NIPAM)₅₅-<i>b</i>-p­(His)_<i>n</i>] micelles remain biologically active and have stimuli responsive capability to kill cancer cells. The self-assembling ability of these hybrid materials into uniform micelles and their efficiency to encapsulate Dox makes them a promising drug carrier to cancer cells. The new chimeric materials thus display tunable properties that can make them useful for a molecular switching device and controlled drug delivery applications needing responses to temperature and pH for the improvement of cancer chemotherapy

Poly(PEGA)‑<i>b</i>‑poly(l‑lysine)‑<i>b</i>‑poly(l‑histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride

A series of poly­(ethylene glycol) methyl ether acrylate-<i>block</i>-poly­(l-lysine)-<i>block</i>-poly­(l-histidine) [p­(PEGA)₃₀-<i>b</i>-p­(Lys)₂₅-<i>b</i>-p­(His)_<i>n</i>] (<i>n</i> = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p­(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01–100 μg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery

Dual Stimuli-Responsive Vesicular Nanospheres Fabricated by Lipopolymer Hybrids for Tumor-Targeted Photodynamic Therapy

Smart delivery system of photosensitizer chlorin e6 (Ce6) has been developed for targeted photodynamic therapy (PDT). Simple self-assemblies of the mixtures comprising soybean lecithin derived phosphatidylcholine (PC), phosphatidylethanolamine-poly­(l-histidine)₄₀ (PE–p­(His)₄₀), and folic acid (FA) conjugated phosphatidylethanolamine-poly­(<i>N</i>-isopropylacrylamide)₄₀ (PE–p­(NIPAM)₄₀–FA) in different ratios yield smart nanospheres characterized by (i) stable and uniform particle size (∼100 nm), (ii) positive surface charge, (iii) high hydrophobic drug (Ce6) loading efficiency up to 45%, (iv) covalently linked targeting moiety, (v) low cytotoxicity, and (vi) smartness showing p­(His) block oriented pH and p­(NIPAM) oriented temperature responsiveness. The Ce6-encapsulated vesicular nanospheres (Ce6@VNS) were used to confirm the efficiency of cellular uptake, intracellular distribution, and phototoxicity against KB tumor cells compared to free Ce6 at different temperature and pH conditions. The Ce6@VNS system showed significant photodynamic therapeutic efficiency on KB cells than free Ce6. A receptor-mediated inhibition study proved the site-specific delivery of Ce6 in targeted tumor cells