Effect of Molecular Structure on Stability of Organic Nanoparticles Formed by Bodipy Dimers.

The objective was to evaluate the stability of organic nanoparticles made from Bodipy dimers. Bodipy dimers with different length of linkers were synthesized via multicomponent Passerini reaction, and could form the fluorescent nanoparticles (FNPs) through nanoprecipitation. Bodipy-dimers FNPs with long chain linker indicated better stability in biological condition than those with short one as revealed by changes of diameter and size distribution.

One-Pot To Synthesize Multifunctional Carbon Dots for Near Infrared Fluorescence Imaging and Photothermal Cancer Therapy.

It is an emerging focus to develop a simple and straightforward strategy to synthesize multifunctional nanomedicines for cancer imaging and treatment. In this work, a new carbon dot (named CyCD) with intrinsic theranostic properties was prepared from a hydrophobic cyanine dye [2-((E)-2-((E)-2-chloro-3-((E)-2-(1-(2-hydroxyethyl)-3,3-dimethylindolin-2-ylidene) ethylidene)cyclohex-1-en-1-yl)vinyl)-1-(2-hydroxyethyl)-3,3-dimethyl-3H-indol-1-ium iodide, CyOH] and poly(ethylene glycol) (PEG800) via a simple solvothermal process. The as-prepared CyCD is well dispersed in water media with an average diameter of 2.

Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer.

Near-Infrared Polymeric Nanoparticles with High Content of Cyanine for Bimodal Imaging and Photothermal Therapy.

The discovery and synthesis of theranostic nanomedicines with high loading of imaging and therapeutic agents is challenging. In this work, a polymer assembling strategy was used to make nanoparticles with exceptionally high loading of theranostic agent. As an example, poly(heptamethine) was synthesized via multicomponent Passerini reaction, and then assembled into nanoparticles in the presence of poly(ethylene glycol)2k-block-poly(d,l-lactide)2k (PEG-PLA) with high heptamethine loading (>50%).

Cooperation of Amphiphilicity and Crystallization for Regulating the Self-Assembly of Poly(ethylene glycol)-block-poly(lactic acid) Copolymers.

Tuning the amphiphilicity of block copolymers has been extensively exploited to manipulate the morphological transition of aggregates. The introduction of crystallizable moieties into the amphiphilic copolymers also offers increasing possibilities for regulating self-assembled structures. In this work, we demonstrate a detailed investigation of the self-assembly behavior of amphiphilic poly(ethylene glycol)-block-poly(l-lactic acid) (PEG-b-PLLA) diblock copolymers with the assistance of a common solvent in aqueous solution.

Comparative acoustic performance and mechanical properties of silk membranes for the repair of chronic tympanic membrane perforations.

The acoustic and mechanical properties of silk membranes of different thicknesses were tested to determine their suitability as a repair material for tympanic membrane perforations. Membranes of different thickness (10-100μm) were tested to determine their frequency response and their resistance to pressure loads in a simulated ear canal model. Their mechanical rigidity to pressure loads was confirmed by tensile testing.

Dual-Sensitive Charge-Conversional Polymeric Prodrug for Efficient Codelivery of Demethylcantharidin and Doxorubicin.

A tumor is a complicated system, and tumor cells are typically heterogeneous in many aspects. Polymeric drug delivery nanocarriers sensitive to a single type of biosignals may not release cargos effectively in all tumor cells, leading to low therapeutic efficacy. To address the challenges, here, we demonstrated a pH/reduction dual-sensitive charge-conversional polymeric prodrug strategy for efficient codelivery.

Tetraphenylethylene-based fluorescent coordination polymers for drug delivery.

New tetraphenylethylene immobilized zirconium-based nanoscale coordination polymers (TPE-NCPs) with morphology-dependent and enhanced AIE behavior have been synthesized for the first time. The TPE-NCPs with high crystallization, strong emission and good biocompatibility can be used as a versatile nanoplatform for efficient drug delivery and bioimaging in living cells.

Time-programmed DCA and oxaliplatin release by multilayered nanofiber mats in prevention of local cancer recurrence following surgery.

Local recurrence following surgery in cancer treatment remains a major clinical challenge. To increase antitumor activity but maintain toxicity in an acceptable level in prevention of local cancer recurrence, we demonstrated a dual drug-loaded multilayered fiber mats strategy, in which DCA and oxaliplatin were co-electrospun into the distinct layer of resultant fabrics and the oxaliplatin-loaded fibers layer was sealed between the basement film layer and other two fibers layers. The dual drug-loaded multilayered fiber mats exhibit time-programmed dual release behavior and synergistic effect upon cancer cells.

Lanthanide-Connecting and Lone-Electron-Pair Active Trigonal-Pyramidal-AsO3 Inducing Nanosized Poly(polyoxotungstate) Aggregates and Their Anticancer Activities.

By virtue of the stereochemical effect of the lone-electron pair located on the trigonal-pyramidal-AsO3 groups and the one-pot self-assembly strategy in the conventional aqueous solution, a series of novel lanthanide-bridging and lone-electron-pair active trigonal-pyramidal-AsO3 inducing nanosized poly(polyoxotungstate) aggregates [H2N(CH3)2]6 Na24H16{[Ln10W16(H2O)30O50](B-α-AsW9O33)8}·97H2O [Ln = Eu(III) (1), Sm(III) (2), Gd(III) (3), Tb(III) (4), Dy(III) (5), Ho(III) (6), Er(III) (7), Tm(III) (8)] were prepared and further characterized by elemental analyses, IR spectra, UV spectra, thermogravimetric (TG) analyses and single-crystal X-ray diffraction. The most remarkable structural feature is that the polyanionic skeleton of {[Ln10W16(H2O)30O50](B-α-AsW9O33)8}(46-) is constructed from eight trivacant Keggin [B-α-AsW9O33](9-) fragments through ten Ln centers and sixteen bridging W atoms in the participation of fifty extraneous oxygen atoms. Notably, 4 and 8 can be stable in the aqueous solution not only for eight days but also in the range of pH = 3.

Single-Stimulus Dual-Drug Sensitive Nanoplatform for Enhanced Photoactivated Therapy.

Photoactivated therapy has become a complementary and attractive modality for traditional cancer treatment. Herein, we demonstrated a novel single-stimulus dual-drug sensitive nanoplatform, Cur-loaded Dex-Pt(N3) nanoparticles (Cur@DPNs) for enhanced photoactivated therapy. The developed Cur@DPNs could be photoactivated by UVA light to simultaneously generate instant reactive oxygen species from Cur for fast photodynamic therapy and release lasting Pt(II) from Pt(N3) for long-acting photochemotherapy.

Self-Assembly of Porphyrin-Paclitaxel Conjugates Into Nanomedicines: Enhanced Cytotoxicity due to Endosomal Escape.

Nanomedicines assembled directly from drug molecules possess several advantages, including precise molecular structure and high content of drugs. Herein, porphyrin-paclitaxel conjugates (Py-s-s-PTX) were synthesized by using a disulfide bond as a linker. The Py-s-s-PTX could self-assemble into nanoparticles (Py-s-s-PTX NPs) with a size of about 100 nm via disulfide-induced assembly.

Reduction-responsive fluorescence off-on BODIPY-camptothecin conjugates for self-reporting drug release.

A reduction-responsive fluorescence off-on theranostic prodrug with self-reporting drug release was constructed based on boron dipyrromethene (BODIPY) and therapeutic drug camptothecin (CPT) with a long flexible disulfide linker. Treatment with dithiothreitol (DTT) induced cleavage of the disulfide bond, followed by intramolecular cyclization reaction to release free CPT, simultaneously perturbing electronic energy transfer (EET) and resulting in enhanced blue and green fluorescence emissions. The changes of the fluorescence ratio over time provided the opportunity for detection and real-time monitoring of drug release at the cellular levels.

BODIPY-containing nanoscale metal-organic frameworks for photodynamic therapy.

BODIPY-immobilized zirconium-based nanoscale metal-organic frameworks (MOFs), named , have been synthesized through solvent-assisted ligand exchange using UiO-typed MOFs and pre-designed BODIPY ligands for the first time. The nanocrystal has been proved to possess good biocompatibility and highly efficient generation of singlet oxygen, which could kill the cancer cells effectively.

Synthesis of the Hemoglobin-Conjugated Polymer Micelles by Thiol Michael Addition Reactions.

Amphiphilic triblock copolymers mPEG-b-PMAC-b-PCL are synthesized using methoxyl poly(ethylene glycol), cyclic carbonic ester monomer including acryloyl group, and ε-caprolactone. Copolymers are self-assembled into core-shell micelles in aqueous solution. Thiolated hemoglobin (Hb) is conjugated with micelles sufficiently through thiol Michael addition reaction to form hemoglobin nanoparticles (HbNs) with 200 nm in diameter.

A dual-responsive nanocapsule disulfide-induced self-assembly for therapeutic agent delivery.

One-step synthesis of fluorescent molecules (SNBDP) containing one disulfide bond and two -nitrobenzyl groups was demonstrated multi-component Passerini reaction. This hydrophobic SNBDP could self-assemble into nanocapsules (SNBDP NCs) in aqueous solution disulfide-induced assembly. The obtained nanocapsules were stable in aqueous solution for several weeks and exhibited enhanced fluorescence when nanocapsules were destroyed due to disaggregation-induced emission.

Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism.

Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid β-oxidation (FAO), which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC)-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis), of CPT1A (an enzyme required for long-chain FAO transport into mitochondria), or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex.

Nanoscale Metal-Organic Framework-Hemoglobin Conjugates.

A metal-organic framework (MOF)-protein conjugate, NH2 -MIL-125(Ti)-hemoglobin [MIL-125(Ti)-Hb], was synthesized by a covalent postmodification strategy. The crystalline structure was maintained after chemical and protein modification. The content of grafted Hb was tuned by the stoichiometric ratio and reached 50 wt % if the mass ratio of MIL-125(Ti)/Hb was 1:1.

Facile microwave-assisted synthesis of benzimidazole scaffolds via Ugi-type three-component condensation (3CC) reactions.

Two series of fused benzimidazoles were synthesized via a facile, one-pot procedure under microwave irradiation. This procedure generated the desired products in high yields and could provide a useful synthetic platform with potential applications in medicinal chemistry.

Doxorubicin-Loaded Carborane-Conjugated Polymeric Nanoparticles as Delivery System for Combination Cancer Therapy.

Carborane-conjugated amphiphilic copolymer nanoparticles were designed to deliver anticancer drugs for the combination of chemotherapy and boron neutron capture therapy (BNCT). Poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2(2-dicarba-closo-dodecarborane)propyloxycarbonyl-propyne carbonate) (PLMB) was synthesized via the versatile reaction between decaborane and side alkynyl groups, and self-assembled with doxorubicin (DOX) to form drug-loaded nanoparticles. These DOX@PLMB nanoparticles could not only suppress the leakage of the boron compounds into the bloodstream due to the covalent bonds between carborane and polymer main chains, but also protect DOX from initial burst release at physiological conditions because of the dihydrogen bonds between DOX and carborane.

Amphiphilic Cyanine-Platinum Conjugates as Fluorescent Nanodrugs.

Two fluorescent nanomedicines based on small molecular cyanine-platinum conjugates have been prepared via a nanoprecipitation method and characterized by transmission electron microscopy (TEM) as well as dynamic light scattering (DLS). The conjugates exhibited an enhanced fluorescence in their nanoparticle formulation compared to that in solution. The nanomedicines could be endocytosed by cancer cells as revealed by confocal laser scanning microscopy (CLSM) and showed high cellular proliferation inhibition.

A dextran-platinum(iv) conjugate as a reduction-responsive carrier for triggered drug release.

Reduction-responsive nano-carriers have been confirmed to be promising for intracellular drug delivery. To develop multifunctional polymer-based drug delivery system, a novel dextran-Pt(iv) conjugate was synthesized by conjugating Pt(iv) to the side chains of the hydrophilic dextran and used for doxorubicin (DOX) delivery. Pt(iv) conjugation could change the hydrophilicity of dextran, leading to the self-assembly of dextran-Pt(iv) conjugates with different morphologies.

Self-Targeting Fluorescent Carbon Dots for Diagnosis of Brain Cancer Cells.

A new type of carbon dots (CD-Asp) with targeting function toward brain cancer glioma was synthesized via a straightforward pyrolysis route by using D-glucose and L-aspartic acid as starting materials. The as-prepared CD-Asp exhibits not only excellent biocompatibility and tunable full-color emission, but also significant capability of targeting C6 glioma cells without the aid of any extra targeting molecules. In vivo fluorescence images showed high-contrast biodistribution of CD-Asp 15 min after tail vein injection.

One-Step Synthesis of Nanoscale Zeolitic Imidazolate Frameworks with High Curcumin Loading for Treatment of Cervical Cancer.

A straightforward nanoprecipitating method was developed to prepare water dispersible curcumin (CCM)-loaded nanoscale zeolitic imidazolate framework-8 (CCM@NZIF-8) nanoparticles (NPs). The as-synthesized CCM@NZIF-8 NPs possess high drug encapsulation efficiency (88.2%), good chemical stability and fast drug release in tumor acidic microenvironments.

Thiadiazole molecules and poly(ethylene glycol)-block-polylactide self-assembled nanoparticles as effective photothermal agents.

A new photothermal nano-agent was obtained by the coprecipitation of 2,5-Bis(2,5-bis(2-thienyl)-N-dodecyl pyrrole) thieno[3,4-b][1,2,5] thiadiazole (TPT-TT) and a biodegradable amphiphilic block copolymer, methoxypoly(ethylene glycol)2K-block-poly(D,L-lactide)2K (mPEG2K-PDLLA2K). TPT-TT, a donor-acceptor-donor (D-A-D) type small molecule, with bis(2-thienyl)-N-alkylpyrrole (TPT) as the donor and thieno[3,4-b]thiadiazole (TT) as the acceptor was a strong near infrared (NIR) absorber, which could convert the absorbed light energy into heat. The formation of TPT-TT nanoparticles (TPT-NPs), which possessed high stability in water, was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM).