"On/off"-switchable crosslinked PTX-nanoformulation with improved precise delivery for NSCLC brain metastases and restrained adverse reaction over nab-PTX.

Non-small cell lung cancer (NSCLC) brain metastases present a significant treatment challenge due to limited drug delivery efficiency and severe adverse reactions. In this study, we address these challenges by designing a "on/off" switchable crosslinked paclitaxel (PTX) nanocarrier, BPM-PD, with novel ultra-pH-sensitive linkages (pH 6.8 to 6.5). BPM-PD demonstrates a distinct "on/off" switchable release of the anti-cancer drug paclitaxel (PTX) in response to the acidic extratumoral microenvironment. The "off" state of BPM-PD@PTX effectively prevents premature drug release in the blood circulation, blood-brain barrier (BBB)/blood-tumor barrier (BTB), and normal brain tissue, surpassing the clinical PTX-nanoformulation (nab-PTX). Meanwhile, the "on" state facilitates precise delivery to NSCLC brain metastases cells. Compared to nab-PTX, BPM-PD@PTX demonstrates improved therapeutic efficacy with a reduced tumor area (only 14.6%) and extended survival duration, while mitigating adverse reactions (over 83.7%) in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), offering a promising approach for the treatment of NSCLC brain metastases. The precise molecular switch also helped to increase the PTX maximum tolerated dose from 25 mg/kg to 45 mg/kg This research contributes to the field of cancer therapeutics and has significant implications for improving the clinical outcomes of NSCLC patients.

Mesoporous-Layered Double Oxide/MCM-41 Composite with Enhanced Catalytic Performance for Cyclopentanone Aldol Condensation.

Layered double oxides are widely employed in catalyzing the aldol condensation for producing biofuels, but its selectivity and stability need to be further improved. Herein, a novel MCM-41-supported Mg-Al-layered double oxide (LDO/MCM-41) was prepared via the in situ integration of a sol-gel process and coprecipitation, followed by calcination. This composite was first employed to catalyze the self-condensation of cyclopentanone for producing high-density cycloalkane precursors. LDO/MCM-41 possessed large specific surface area, uniform pore size distribution, abundant medium basic sites and Bronsted acid sites. Compared with the bulk LDO, LDO/MCM-41 exhibited a higher selectivity for C10 and C15 oxygenates at 150 °C (93.4% vs. 84.6%). The selectivity for C15 was especially enhanced on LDO/MCM-41, which was three times greater than that on LDO. The stability test showed that naked LDO with stronger basic strength had a rapid initial activity, while it suffered an obvious deactivation due to its poor carbon balance. LDO/MCM-41 with lower basic strength had an enhanced stability even with a lower initial activity. Under the optimum conditions (50% LDO loading, 170 °C, 7 h), the cyclopentanone conversion on LDO/MCM-41 reached 77.8%, with a 60% yield of C10 and 15.2% yield of C15.

Programmed-response cross-linked nanocarrier for multidrug-resistant ovarian cancer treatment.

The application of numerous chemotherapeutic drugs has been limited due to poor solubility, adverse side effects, and even multidrug resistance in patients. Polymeric micelles with reversibly cross-linked structures provide a promising solution to these issues. Herein, we optimized and synthesized programable-released disulfide cross-linked micelle (PDCM) based on our previous well-defined dendrimers to deliver the antitumor drug betulinic acid (BA) and paclitaxel (PDCM@PTX) and evaluated the therapeutic efficacy of multidrug-resistant (MDR) simulative orthotopic intraperitoneal ovarian cancer mice models. Comprehensive results demonstrated that PDCM@PTX formed stable nanoparticles able to improve the pharmacokinetic profile and circulation time of PTX, allowing for increased tumor penetration. Furthermore, in the tumor microenvironment, the programable-switches (ester bonds and disulfide cross-linking) of PDCM@PTX were cleaved by the high concentration of glutathione (tumor microenvironment) and esterase (intracellular) present in the tumor, allowing for in situ release of PTX and BA, resulting in intensive therapeutic efficacy in MDR ovarian cancer.

On-demand targeting nanotheranostics with stimuli-responsive releasing property to improve delivery efficiency to cancer.

Nanocarriers have great potential to enhance drug delivery efficiency and therapeutic effect for various cancers. However, premature drug leakage and non-specific targeting still limit the delivery efficiency. Here, we present a smart on-demand targeting nanotheranostic system (PO-PB@SPIOs) with stimuli-responsive releasing property to improve the delivery efficiency for ovarian cancer. This delivery system prevents premature drug leakage via boronate ester linkages and shields the targeting moieties (phenylboronic acid) from non-specific binding when circulating in the blood. The PO-PB@SPIOs would release the tumor-targeting payload (PB) in response to the tumor microenvironment. Then, PB was able to target the overexpressed sialic acids on tumor cells. The significant improvement of delivery efficiency was demonstrated in vivo by a significantly enhanced signal in near-infrared-fluorescence (NIRF)/magnetic-resonance (MR) imaging (5-fold higher) and a remarkable photo-thermal therapeutic effect (complete cure rate (CCR) up to 80%). Furthermore, due to the on-demand targeting and stimuli-responsive releasing strategy, this nanotheranostic system shows a greater delivery efficiency even than the active-targeting small molecules or control nanoformulations. We believe this delicate design has great potential to develop novel drug nanoformulation.

TMT-Based Quantitative Proteomics Analysis Reveals the Panoramic Pharmacological Molecular Mechanism of ß-Elemonic Acid Inhibition of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide but has limited available therapeutic methods; therefore, there is a need to develop highly efficient prevention and treatment strategies. Here, we investigated the anti-cancer activity of ß-elemonic acid (EA) in CRC in vitro and in vivo. Our results showed that EA inhibited cell proliferation and migration in the CRC cell lines SW480 and HCT116. Moreover, EA significantly suppressed the growth of transplanted colorectal tumors in nude mice. Interestingly, high-throughput tandem mass tag (TMT)-based quantitative proteomics indicated that EA mainly targets tumor mitochondria and attenuates the translation of 54 mitochondrial ribosome proteins, many of which are discovered significantly upregulated in clinical CRC patients. More interestingly, EA at a low concentration (lower than 15 µg/ml) repressed the cell cycle by downregulating CDK1, CDK6, and CDC20, whereas at a high concentration (higher than 15 µg/ml), caused a non-apoptotic cell death-ferroptosis via downregulating ferritin (FTL) and upregulating transferrin (TF), ferroxidase (CP), and acyl-CoA synthetase long-chain family member 4 (ACSL4). This is the first report on the panoramic molecular mechanism of EA against CRC, which would make great contributions to developing a novel drug for colorectal cancer therapy.

Facile one-step synthesis of 3D honeycomb-like porous chitosan bead inlaid with MnFe bimetallic oxide nanoparticles for enhanced degradation of dye pollutant.

Developing a sustainable, efficient and recyclable heterogeneous Fenton-like catalyst is important to wastewater treatment. Herein, well-dispersed MnO2 and Fe3O4 nanoparticles inlaid in chitosan beads (MnO2-Fe3O4/CH) was firstly fabricated and employed in the degradation of methylene blue (MB). The bead was prepared via a facile one-step method by dropwise addition of chitosan-metal salt solution into alkaline solution. Comparing with monometallic chitosan beads (MnO2/CH, Fe3O4/CH) and naked MnO2-Fe3O4, MnO2-Fe3O4/CH displayed significantly higher activity for MB degradation with the assistance of hydrogen peroxide (H2O2), finally removing 96.8% MB under the optimal conditions (50 mg L-1 MB, 4.0 g L-1 catalyst, 30 g L-1 H2O2, pH = 7, 60 min). Based on a series of characterizations, the large surface area (60.1 m2 g-1), well-developed porosity (0.3 cm3 g-1), and intensified electron transport of MnO2-Fe3O4/CH consequently enhanced the catalytic performance via a synergistic effect. Because the specific porous structure of MnO2-Fe3O4/CH facilitated the adsorption/diffusion of reactants and exposure of active sites. Meanwhile, the electron transfer from Mn3+ to Fe3+ accelerated the Fe3+/Fe2+ cycle, which favored the production of dominant reactive species hydroxyl radical for MB degradation. Besides, the magnetic beads could be easily collected from the solution and reused for five times with a negligible leaching.

Immobilization of chitosan-templated MnO2 nanoparticles onto filter paper by redox method as a retrievable Fenton-like dip catalyst.

By exploiting the hydrophilicity of cellulose filter paper (FP) and the excellent chelating property of chitosan (CH) for Mn2+, we have designed an efficient and retrievable dip catalyst MnO2/CH-FP for Fenton-like degradation of methylene blue (MB) over a wide pH range from 2.8 to 11.2. The MnO2 nanoparticles were uniformly immobilized in the CH-FP matrix by in-situ redox precipitation method where Mn(NO3)2 was treated with KMnO4 at mild conditions. A series of MnO2/CH-FP hybrids with different MnO2 loading were fabricated via varying concentration of Mn(NO3)2 solution, and their structure-function relationships were discussed based on detailed characterization. The optimal catalyst 1.0MnO2/CH-FP could cooperate with multiple low-concentration dosages of H2O2 to efficiently degrade 95.6% MB in 90 min (50 mg L-1 MB, 1 g L-1 catalyst, 30 mg L-1 H2O2, pH 7). It is also shown that 1.0MnO2/CH-FP could still keep 83.3% degradation efficiency of MB after six cycles. Moreover, the activity of this composite greatly surpassed that of bare MnO2 for nearly 50%, owing to its larger surface area and more accessible active sites. This method for preparing MnO2/CH-FP could effectively avoid the agglomeration of MnO2 nanoparticles and make the reaction turn on/off almost instantaneously by mere insertion/removal.

The Toxicity Phenomenon and the Related Occurrence in Metal and Metal Oxide Nanoparticles: A Brief Review From the Biomedical Perspective.

Thousands of different nanoparticles (NPs) involve in our daily life with various origins from food, cosmetics, drugs, etc. It is believed that decreasing the size of materials up to nanometer levels can facilitate their unfavorable absorption since they can pass the natural barriers of live tissues and organs even, they can go across the relatively impermeable membranes. The interaction of these NPs with the biological environment disturbs the natural functions of cells and its components and cause health issues. In the lack of the detailed and comprehensive standard protocols about the toxicity of NPs materials, their control, and effects, this review study focuses on the current research literature about the related factors in toxicity of NPs such as size, concentration, etc. with an emphasis on metal and metal oxide nanoparticles. The goal of the study is to highlight their potential hazard and the advancement of green non-cytotoxic nanomaterials with safe threshold dose levels to resolve the toxicity issues. This study supports the NPs design along with minimizing the adverse effects of nanoparticles especially those used in biological treatments.

Partial Cu ion exchange induced triangle hexagonal Mn0.45Cu0.05Cd0.5S nanocrystals for enhanced photocatalytic hydrogen evolution.

High crystallinity triangle hexagonal Mn0.45Cu0.05Cd0.5S was obtained by partial Cu ion exchange treatment on colloidal pristine Mn0.5Cd0.5S nanorods. The Mn0.45Cu0.05Cd0.5S nanotriangles exhibited a high hydrogen yield of 147 921 µmol g-1 h-1 under visible light irradiation, about 7.4 times higher than that of pristine Mn0.5Cd0.5S.

Zwitterionic polymer chain-assisted lysozyme imprinted core-shell carbon microspheres with enhanced recognition and selectivity.

Constructing imprinting materials with high recognition and selectivity for protein is an always challenge in protein imprinting technology (PIT). In this work, upon the participating of a zwitterionic polymer chain (Poly (1-vinyl-3-sulfopropylimidazolium), PVSP), a lysozyme imprinted core-shell carbon microsphere (CFC-PVSP@MIPs) was prepared by combining template immobilization method and surface imprinting technology. The carboxyl-functionalized carbon microspheres as substrate provided the CFC-PVSP@MIPs satisfactory adsorption capacity (68.1 mg g-1), while the dopamine as a functional monomer and crosslinker allowed the imprinted microspheres to have a thin imprinted shell, thus endowing them a fast adsorption equilibrium rate (120 min). In addition, PVSP could be tightly bound to the imprinted layer through non-covalent interaction, which not only simplified the preparation process of CFC-PVSP@MIPs, but also reduced the non-specific adsorption of imprinted material on proteins. Therefore, the resulting CFC-PVSP@MIPs exhibited a more superior recognition ability towards lysozyme with imprinting factor value of 3.10, compared with the PVSP-free imprinted microsphere (imprinting factor value 1.93). Furthermore, benefiting from the characteristics of zwitterionic groups, CFC-PVSP@MIPs also revealed stronger selectivity in competitive adsorption studies of binary protein mixture samples. Consequently, the proposed strategy would be a promising and convenient way to obtain protein imprinted material with high recognition ability, thus would be conducive to further development and application of PIT.

Sequential Targeting in Crosslinking Nanotheranostics for Tackling the Multibarriers of Brain Tumors.

The efficacy of therapeutics for brain tumors is seriously hampered by multiple barriers to drug delivery, including severe destabilizing effects in the blood circulation, the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB), and limited tumor uptake. Here, a sequential targeting in crosslinking (STICK) nanodelivery strategy is presented to circumvent these important physiological barriers to improve drug delivery to brain tumors. STICK nanoparticles (STICK-NPs) can sequentially target BBB/BBTB and brain tumor cells with surface maltobionic acid (MA) and 4-carboxyphenylboronic acid (CBA), respectively, and simultaneously enhance nanoparticle stability with pH-responsive crosslinkages formed by MA and CBA in situ. STICK-NPs exhibit prolonged circulation time (17-fold higher area under curve) than the free agent, allowing increased opportunities to transpass the BBB/BBTB via glucose-transporter-mediated transcytosis by MA. The tumor acidic environment then triggers the transformation of the STICK-NPs into smaller nanoparticles and reveals a secondary CBA targeting moiety for deep tumor penetration and enhanced uptake in tumor cells. STICK-NPs significantly inhibit tumor growth and prolong the survival time with limited toxicity in mice with aggressive and chemoresistant diffuse intrinsic pontine glioma. This formulation tackles multiple physiological barriers on-demand with a simple and smart STICK design. Therefore, these features allow STICK-NPs to unleash the potential of brain tumor therapeutics to improve their treatment efficacy.

Valorization of humin as a glucose derivative to fabricate a porous carbon catalyst for esterification and hydroxyalkylation/alkylation.

A challenge of today's industry is to transform low-value side products into more value-added materials. The acid-catalyzed conversion of hemi(cellulose) to platform chemicals in green chemical/fuel production and biorefinery yields large formation of insoluble byproduct called humin. Herein, humin obtained from dehydration of glucose was transformed into a novel class of effective carbonaceous solid acid catalyst for the first time via low-temperature pyrolysis followed by sulfonation. A range of preparation conditions were investigated, and the structure-function relationships of the resulting catalysts were also discussed based on the analysis of structure and composition. Comparing with the glucose-derived carbon catalyst, the humin-derived catalyst has substantially larger surface area and higher SO3H density, which enable it to display higher catalytic activity and efficiency not only in esterification of levulinic acid and n-butanol (yield = 95.0%, 373 K), but also in hydroxyalkylation/alkylation of 2-methylfuran and furfural (yield = 64.2%, 323 K). Additionally, the catalyst could be repeatedly employed for at least four cycles without obvious deactivation, exhibiting good reusability. This work provides a green method to convert humin byproduct into economic and eco-friendly solid acid catalyst and may contribute to a holistic approach for biomass utilization.

Immobilization of BSA on ionic liquid functionalized magnetic Fe3O4 nanoparticles for use in surface imprinting strategy.

Combining template immobilization with surface imprinting technology is an effective strategy to overcome the difficulties associated with macromolecular template removal and to achieve high specific recognition ability. In this work, ionic liquid functionalized Fe3O4 nanoparticles were prepared via a simple two-step modification process and were used as substrate to immobilize bovine serum albumin (BSA). The zeta potential study revealed immobilization of BSA on the nanoparticles through multiple interactions, and the immobilization capacity was about nine times higher compared with that of bare Fe3O4. Subsequently, dopamine was utilized as functional monomer to prepare BSA surface imprinted nanoparticles. Fourier transform infrared spectroscopy, thermo-gravimetric analysis and transmission electron microscopy verified the successful preparation of BSA imprinted nanoparticles with core-shell structure. The influence of imprinted layer thickness on recognition ability of imprinted nanoparticles was investigated, and the results suggested that 20nm was an optimum thickness to achieve the best recognition ability. The adsorption isotherm studies showed that the imprinted nanoparticles had a significantly higher adsorption capacity and stronger binding affinity than the non-imprinted ones. Furthermore, the selective as well as the competitive adsorption studies revealed higher selectivity and recognition ability of the imprinted nanoparticles for BSA. Therefore, the proposed strategy is an effective way to obtain protein imprinted polymers with high adsorption capacity and good recognition ability, thus would be beneficial for the further development and application of protein imprinting technology.

Synthesis of high density aviation fuel with cyclopentanol derived from lignocellulose.

For the first time, renewable high density aviation fuels were synthesized at high overall yield (95.6%) by the Guerbet reaction of cyclopentanol which can be derived from lignocellulose, followed by the hydrodeoxygenation (HDO). The solvent-free Guerbet reaction of cyclopentanol was carried out under the co-catalysis of solid bases and Raney metals. Among the investigated catalyst systems, the combinations of magnesium-aluminium hydrotalcite (MgAl-HT) and Raney Ni (or Raney Co) exhibited the best performances. Over them, high carbon yield (96.7%) of C10 and C15 oxygenates was achieved. The Guerbet reaction products were further hydrodeoxygenated to bi(cyclopentane) and tri(cyclopentane) over a series of Ni catalysts. These alkanes have high densities (0.86 g mL(-1) and 0.91 g mL(-1)) and can be used as high density aviation fuels or additives to bio-jet fuel. Among the investigated HDO catalysts, the 35 wt.% Ni-SiO2-DP prepared by deposition-precipitation method exhibited the highest activity.

Synthesis of renewable high-density fuels using cyclopentanone derived from lignocellulose.

By the combination of solvent-free aldol condensation and one-step hydrodeoxygenation under mild reaction conditions, a high-density (0.866 g mL(-1)) bicyclic C10 hydrocarbon was synthesized in high overall yield (up to 80%) using cyclopentanone derived from lignocellulose.

Solvent-free synthesis of C10 and C11 branched alkanes from furfural and methyl isobutyl ketone.

Our best results jet: C10 and C11 branched alkanes, with low freezing points, are synthesized through the aldol condensation of furfural and methyl isobutyl ketone from lignocellulose, which is then followed by hydrodeoxygenation. These jet-fuel-range alkanes are obtained in high overall yields (≈90%) under solvent-free conditions.

Synthesis of renewable diesel with the 2-methylfuran, butanal and acetone derived from lignocellulose.

In this work, the hydroxyalkylation/alkylation of 2-methylfuran (2-MF) with acetone and butanal was investigated over a series of solid acid catalysts. Among the investigated candidates, Nafion-212 resin demonstrated the highest activity and stability for both reactions. Butanal is more reactive than acetone in hydroxyalkylation/alkylation, which can be rationalized by the steric and electronic effects of alkyl group. Finally, the hydroxyalkylation/alkylation products as prepared were directly hydrodeoxygenated over Pd/C, Pt/C and Ni-WxC/C catalysts. Evidently higher carbon yields to diesel were obtained when hydroxyalkylation/alkylation product of 2-MF with butanal was used as the feedstock. This can be considered as another advantage of 2-MF-butanal route. It is interesting that Ni-WxC/C catalyst exhibited excellent catalytic performance and good stability in the hydrodeoxygenation of hydroxyalkylation/alkylation products, which made it a promising substitute for the noble metal catalysts.