NIR-II-absorbing diimmonium polymer agent achieves excellent photothermal therapy with induction of tumor immunogenic cell death.

Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000-1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.

Volatilization characteristics and risk evaluation of heavy metals during the pyrolysis and combustion of rubber waste without or with molecular sieves.

The volatilization characteristics and risk evaluation of heavy metals (As, Cd, Co ,Cr, Cu, Ni, Pb, Zn, and Ti) during pyrolysis and combustion of rubber waste with or without molecular sieves (MS) were studied. The addition of MS during pyrolysis inhibited the volatilization of As and promoted the volatilization of Ni and Co, while during combustion it inhibited the volatilization of Pb, Zn and promoted the volatilization of Cu. For Cd, Cr, Ni, Zn and Ti, their volatilization rates during pyrolysis were significantly higher than those during combustion, whereas for As and Cu, the volatilization rates during pyrolysis were lower than those during combustion. Risk evaluation of gaseous heavy metals was exhibited based on the Potential Ecological Risk Index (RI) method. The potential ecological risk during combustion was generally lower than that during pyrolysis. The research results provide important information of heavy metals control during waste thermal treatment.

Facile Fabrication of Oxidation-Responsive Polymeric Nanoparticles for Effective Anticancer Drug Delivery.

Reactive oxygen species (ROS) are highly overproduced in cancerous tissues, and thus oxidation-responsive nanoparticles (NPs) have emerged as a promising drug carrier for cancer-targeted drug delivery. In this study, we successfully synthesized poly(vanillyl alcohol- co-oxalate) (PVAX) polymer with an excellent ROS-responsive capacity. A well-established emulsion-solvent evaporation method was used to fabricate PVAX-based curcumin (CUR)-loaded NPs (PVAX-NPs) and their counterparts (poly(lactic- co-glycolic acid)-based CUR-loaded NPs, PLGA-NPs). It was found that these NPs had a hydrodynamic particle size of approximately 245 nm, narrow size distribution (polydispersity index less than 0.1), negative zeta potential (around -18 mV), smooth surface appearance, and high drug encapsulation efficiency. Moreover, we found that the CUR release rate of PVAX-NPs was greatly increased in the presence of a hydrogen peroxide-rich environment due to the cleavage of polyoxalate ester bonds in PVAX polymer, resulting in the evenly distribution of CUR within the whole cancer cells. More importantly, PVAX-NPs exhibited much stronger anticancer activities and pro-apoptotic capacities than PLGA-NPs both in vitro and in vivo. These results clearly demonstrate that these ROS-responsive PVAX-NPs can be exploited as a robust anticancer drug delivery platform in chemotherapy.

Starburst Diblock Polyprodrugs: Reduction-Responsive Unimolecular Micelles with High Drug Loading and Robust Micellar Stability for Programmed Delivery of Anticancer Drugs.

Polymeric prodrug based on therapeutic nanomedicine has demonstrated great promise for effective tumor growth inhibition, however, the drawbacks of low drug-loading and weak micellar stability limit its application for clinical cancer therapy. Herein, a reduction-responsive starburst block copolymer prodrug CCP [ß-cyclodextrin (ß-CD)-PCPTXX-POEGMA, XX: SS or CC] has been developed for cancer therapy. And CCP is composed of ß-CD-Br core with multiple reactive sites, as well as a diblock copolymer containing hydrophobic polymerized camptothecin (PCPT) prodrug chain and hydrophilic poly[(ethylene glycol) methyl ether methacrylate] (OEGMA) chain. A family of CCP polymeric prodrugs with different drug loading contents (up to 25%) and various sizes of unimolecular micelles (UMs) (around 30 nm) were obtained by adjusting the block ratio of PCPTXX and POEGMA. On account of the amphiphilic structure feature, CPP could take shape water-soluble UMs in aqueous medium with excellent micellar stability. Under imitatively reductive tumor microenvironment, anticancer drug CPT could rapidly escape from CCP UMs in terms of disulfide bond breakage. However, this behavior is strongly refrained in the physiological environment. In vitro and in vivo outcome confirmed that CCP UMs showed excellent performance of sufficient tumor accumulation, high-efficiency tumor growth inhibition and low-toxicity for healthy tissues. Based on these gratifying therapeutic efficacy, it is believed that as-present starburst prodrug strategy can offer a brand-new insight for high-efficiency therapeutic nanoplatforms for chemotherapy application.

Acid-Activatable Theranostic Unimolecular Micelles Composed of Amphiphilic Star-like Polymeric Prodrug with High Drug Loading for Enhanced Cancer Therapy.

Stimuli-responsive nanomedicine with theranostic functionalities with reduced side-effects has attracted growing attention, although there are some major obstacles to overcome before clinical applications. Herein, we present an acid-activatable theranostic unimolecular micelles based on amphiphilic star-like polymeric prodrug to systematically address typical existing issues. This smart polymeric prodrug has a preferable size of about 35 nm and strong micellar stability in aqueous solution, which is beneficial to long-term blood circulation and efficient extravasation from tumoral vessels. Remarkably, the polymeric prodrug has a high drug loading rate up to 53.1 wt%, which induces considerably higher cytotoxicity against tumor cells (HeLa cells and MCF-7 cells) than normal cells (HUVEC cells) suggesting a spontaneous tumor-specific targeting capability. Moreover, the polymeric prodrug can serve as a fluorescent nanoprobe activated by the acidic microenvironment in tumor cells, which can be used as a promising platform for tumor diagnosis. The superior antitumor effect in this in vitro study demonstrates the potential of this prodrug as a promising platform for drug delivery and cancer therapy.

Low-cost pyrolysis of biomass-derived nitrogen-doped porous carbon: Chlorella vulgaris replaces melamine as a nitrogen source.

Porous carbon generated from biomass has a rich pore structure, is inexpensive, and has a lot of promise for use as a carbon material for energy storage devices. In this work, nitrogen-doped porous carbon was prepared by co-pyrolysis using bagasse as the precursor and chlorella as the nitrogen source. ZnCl2 acts as both an activator and a nitrogen fixer during activation to generate pores and reduce nitrogen loss. The thermal weight loss experiments showed that the pyrolysis temperatures of bagasse and chlorella overlap, which created the possibility for the synthesis of nitrogen-rich biochar. The optimum sample (ZBC@C-5) possessed a surface area of 1508 m2g-1 with abundant nitrogen-containing functional groups. ZBC@C-5 in the three-electrode system exhibited 244.1F/g at 0.5A/g, which was extremely close to ZBC@M made with melamine as the nitrogen source. This provides new opportunities for the use of low-cost nitrogen sources. Furthermore, the devices exhibit better voltage retention (39%) and capacitance retention (96.3%). The goal of this research is to find a low cost, and effective method for creating nitrogen-doped porous carbon materials with better electrochemical performance for highly valuable applications using bagasse and chlorella.

Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system.

Colorectal carcinoma (CRC) has become one of the most prevalent malignant tumors and exploring a potential therapeutic strategy with diminished drug-associated adverse effects to combat CRC is urgent. Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Investigations in vitro demonstrated that polymer encapsulation endowed the system with a pH-dependent disassembly behavior (pHt 6.37), which preferentially selected cancerous cells with a favorable dose reduction (dose reduction index (DRI) of HCFU was 4.09). Moreover, the growth of CRC in tumor-bearing mice was effectively suppressed, with tumor suppression rates up to 94.74%, and a combination index (CI) value of less than one (CI = 0.41 for CT26 cell lines), indicating a significant synergistic therapeutic effect. Histological analysis of the tumor micro-vessel density and enzyme-linked immunosorbent assay (ELISA) tests indicated that the system increased TNF-α and IFN-ß levels in serum. Therefore, this research introduces a pH-responsive polymer-based theranostic platform with great potential for immune-chemotherapeutic and anti-vascular combination therapy of CRC.

Catalytic co-pyrolysis of microwave pretreated chili straw and polypropylene to produce hydrocarbons-rich bio-oil.

In this work, the kinetic behavior and products of the co-pyrolysis of chili straw (CS) and polypropylene (PP) of distinguishing conditions (blending ratios, addition of catalysts, and microwave pretreatment at different power) had been investigated. Co-pyrolysis effectively reduced the proportion of oxygenated composition in CS, and the Oxygenated composition of 5CS5PP decreased by 76.69% compared to CS. When HZSM-5 was added, the aromatic hydrocarbons in the product increased from 4.46% to 17.34%, and the final residual mass decreased from 12.75% to 7.71%, illustrating that HZSM-5 had a positive effect on co-pyrolysis. Compared with P0HZSM-5, the microwave pretreatment at a higher power level of 567 W reduced the oxygenated composition from 17.41% to 13.09%, and the weight loss peak in the first stage increased from -18.11%/min to -19.94%/min. At the same time, the activation energy decreased from 271.25 kJ/mol to 231.13 kJ/mol.

Comparison of Autogenous Tooth Materials and Other Bone Grafts.

Autogenous odontogenic materials are a new, highly biocompatible option for jaw restoration. The inorganic component of autogenous teeth acts as a scaffold to maintain the volume and enable donor cell attachment and proliferation; the organic component contains various growth factors that promote bone reconstruction and repair. The composition of dentin is similar to that of bone, which can be a rationale for promoting bone reconstruction. Recent advances have been made in the field of autogenous odontogenic materials, and studies have confirmed their safety and feasibility after successful clinical application. Autogenous odontogenic materials have unique characteristics compared with other bone-repair materials, such as the conventional autogenous, allogeneic, xenogeneic, and alloplastic bone substitutes. To encourage further research into odontogenic bone grafts, we compared the composition, osteogenesis, and development of autogenous odontogenic materials with those of other bone grafts. In conclusion, odontogenic bone grafts should be classified as a novel bone substitute.

Co-hydrothermal carbonization of water hyacinth and polyvinyl chloride: Optimization of process parameters and characterization of hydrochar.

The co-hydrothermal carbonization (co-HTC) of water hyacinth (WH) and polyvinyl chloride (PVC) was investigated and the response surface methodology, which could deduce the interactions among process parameters and establish reliable mathematical models forecasting the behavior of output variables, was implemented to optimize process parameters, including reaction temperature (200-260 °C), residence time (30-90 min) and WH/PVC mixing ratios (0.5-2). Statistical analysis revealed that reaction temperature was the predominant parameter affecting hydrochar dechlorination efficiency, yield, calorific value, energetic recovery efficiency and electricity consumption. The predicted condition of 200-30-0.5 could simultaneously acquire the optimal energetic recovery efficiency and electricity consumption for producing unit HHV, corresponding to 94.96% and 13.81. The characterization results identified that hydrochar could harvest lower H/C and O/C ratios as well as superior inorganics removal ability. Overall, the co-HTC of WH and PVC could definitely be a promising alternative to bridge the gap from solid wastes to renewable fuels.

Co-hydrothermal carbonization of polyvinyl chloride and corncob for clean solid fuel production.

The improvement of dechlorination efficiency remains an important challenge during co-hydrothermal carbonization (co-HTC) of polyvinyl chloride (PVC). In this work, co-HTC of biomass and PVC at different mixing ratios (30%-70%) and feed-water pH (3-11) was proposed to further improve the dechlorination efficiency. In terms of water solvent, the dechlorination efficiency of co-HTC process (87.83%-93.63%) was higher than that of individual HTC of polyvinyl chloride (87.44%). In case of organic acid/alkali solvents, the dechlorination efficiency further increased to 95.20% at pH = 5. Particularly, the hydrochars derived from co-HTC showed high fuel ratio (0.71-0.99) and their higher heating value reached approximately 29.16-32.83 MJ/kg. The TGA results showed that the combustion behaviors of hydrochars derived from co-HTC got better compared with that of hydrochar derived from PVC. Therefore, co-HTC can realize sustainable utilization of PVC towards clean solid fuels. This work also sheds light on the potential of organic acid in dechlorination treatment.

General distributed activation energy model (G-DAEM) on co-pyrolysis kinetics of bagasse and sewage sludge.

In this work, pyrolysis kinetic evolution of mixture of bagasse and sewage sludge with 10%, 30% and 50% (respect to dry initial weight). In terms of kinetic mechanism, the uncertainty of the activation energy obtained by mode-free method was barely known. We found that increasing number of heating rates made result more reliable, but the modeling process more dependent on redundant experiments with extra data. We adapted a novel general distributed activation energy model (G-DAEM) with 5 pseudocomponents for the analysis of kinetic evolution with proposing a more applicable approximation to the general temperature integral. The G-DAEM was trained by data for 20 K/min, and the predictions were performed on data for 15 K/min and 25 K/min. The predictions were well matched to the experimental data. The G-DAEM enhances modeling efficiency of kinetics and provides a effective pathway for high precise model of complicated co-pyrolysis process.

Codelivery of doxorubicin and camptothecin by dual-responsive unimolecular micelle-based ß-cyclodextrin for enhanced chemotherapy.

Tumor microenvironment (TME)-induced drug delivery technology is a promising strategy for improving low drug accumulation efficiency, short blood circulation and weak therapeutic effect. In this work, a dual-responsive (reduction- and pH-responsive) polyprodrug nanoreactor based on ß-cyclodextrin (ß-CD) was constructed for combinational chemotherapy. Specifically, the dual-responsive star polymeric prodrug was synthesized by atom transfer radical polymerization (ATRP) based on a starburst initiator of ß-CD-Br. The obtained polyprodrug contained a hydrophilic chain of poly-(ethylene glycol) methyl ether methacrylate (POEGMA) and a hydrophobic part of camptothecin (CPT) prodrug and poly[2-(diisopropylamino)ethyl methacrylate] (PDPA), denoted as ß-CD-PDPA-POEGMA-PCPT (CCDO for short). The obtained CCDO could form stable unimolecular micelles, which could be efficiently internalized by cancer cells. To enhance the curative effect, the anticancer agent doxorubicin (DOX) could be encapsulated into the hydrophobic cavity of the CCDO by hydrophobic-hydrophobic interaction. In vitro drug release studies showed that the obtained CCDO/DOX micelles controlled the release of active CPT and DOX occurring in a reductive environment and at low pH. In vitro cytotoxicity results suggested that the anticancer efficacy of dual-responsive CCDO/DOX micelles was superior to that of CCDO micelles. In addition, in vivo results verified good blood compatibility of the unimolecular micelles. This integrated dual-responsive drug delivery system may solve the low drug loading and poor controlled release problems found in traditional polymer-based drug carriers, providing an innovative and promising route for cancer therapy.

Characteristics of co-hydrothermal carbonization on polyvinyl chloride wastes with bamboo.

The PVC waste and bamboo were treated by co-hydrothermal carbonization (co-HTC) at three different temperatures. The inorganic-Cl could be removed from the carbon rich solid products (hydrochar) in the form of HCl via hydrolysis, elimination, substitution and aromatization. Due to the high carbon content, the hydrochar could be applied as premium fuel. Bamboo had a synergistic effect on dechlorination with PVC in the HTC process. The bamboo could accelerate the HTC dechlorination of PVC at 200°C because it strengthened the substitution of Cl with OH. While at 230 and 260°C, the existence of bamboo hindered the dechlorination of PVC in HTC. Thermogravimetric analysis showed the combustion performance of hydrochar was better than the raw samples at 200°C. Owing to the low chlorine content, low ignition temperature and the superior combustion performance, the M-260 can be adopted as alternative fuels for coal.

Co-pyrolysis kinetics of sewage sludge and bagasse using multiple normal distributed activation energy model (M-DAEM).

In this study, the kinetic models of bagasse, sewage sludge and their mixture were established by the multiple normal distributed activation energy model. Blending with sewage sludge, the initial temperature declined from 437 K to 418 K. The pyrolytic species could be divided into five categories, including analogous hemicelluloses I, hemicelluloses II, cellulose, lignin and bio-char. In these species, the average activation energies and the deviations situated at reasonable ranges of 166.4673-323.7261 kJ/mol and 0.1063-35.2973 kJ/mol, respectively, which were conformed to the references. The kinetic models were well matched to experimental data, and the R2 were greater than 99.999%y. In the local sensitivity analysis, the distributed average activation energy had stronger effect on the robustness than other kinetic parameters. And the content of pyrolytic species determined which series of kinetic parameters were more important.

Carboxyl of Poly(D,L-lactide-co-glycolide) Nanoparticles of Perfluorooctyl Bromide for Ultrasonic Imaging of Tumor.

Perfluorooctyl bromide (PFOB) enclosed nanoparticles (NPs) as ultrasonic contrasts have shown promising results in the recent years. However, NPs display poor contrast enhancement in vivo. In this work, we used the copolymers poly(lactide-co-glycolide) carboxylic acid (PLGA-COOH) and poly(lactide-co- glycolide) poly(ethylene glycol) carboxylic acid (PLGA-PEG-COOH) as a shell to encapsulate PFOB to prepare a nanoultrasonic contrast agent. The NPs were small and uniform (210.6 ± 2.9 nm with a polydispersity index of 0.129 ± 0.016) with a complete shell nuclear structure under the transmission electron microscopy (TEM). In vitro, when concentration of NPs was ≥10 mg/ml and clinical diagnostic frequency was ≥9 MHz, NPs produced intensive enhancement of ultrasonic gray-scale signals. NPs could produce stable and obvious gray enhancement with high mechanical index (MI) (MI > 0.6). In vivo, the NPs offered good ultrasound enhancement in tumor after more than 24 h and optical imaging also indicated that NPs were mainly located at tumor site. Subsequent analysis confirmed that large accumulation of fluorescence was observed in the frozen section of the tumor tissue. All these results caused the conclusion that NPs encapsulated PFOB has achieved tumor-selective imaging in vivo.

Reduction stimuli-responsive unimolecular polymeric prodrug based on amphiphilic dextran-framework for antitumor drug delivery.

We report a new reduction-responsive amphiphilic polymeric prodrug based on a linear dextran (DEX) backbone, which was conjugated with an hydrophobic camptothecin (CPT) prodrug block and an hydrophilic poly[poly(ethylene glycol) methyl ether methacrylate] (POEGMA) block [DEX-PCPT-b-POEGMA (DCO)] by atom transfer radical polymerization (ATRP). This amphiphilic prodrug has a unique molecular structure with prominent features, including strong practicability for methacrylate prodrug monomer, high drug loading rate (up to 23wt%), adjustable proportion of hydrophobic and hydrophobic portions, superior stability in aqueous solution, and easy access to cells. Introduction of a disulfide bond linker between the drug and the carrier can realize the function of reduction-responsive controlled drug-release. The experimental study indicated that the prodrug exhibited notable antitumor activity against HeLa cells and MCF-7 cells in vitro. Compared to similar DCO prodrug based on double carbon bond, the disulfide bond-conjugated DCO prodrug induced higher level of tumor cell apoptosis. Considering the drug-loading efficiency, micellar stability, cost of preparation and controlled drug release, the presented prodrug is more advantageous than traditional unimolecular prodrug and represents a promising approach for design of stimuli-responsive polymeric prodrug for effective cancer therapeutics.

Irinotecan delivery by unimolecular micelles composed of reduction-responsive star-like polymeric prodrug with high drug loading for enhanced cancer therapy.

Nanomedicine based polymeric prodrug have showed high impact in the inhibition of tumor growth due to its high therapeutic efficiency and improved biocompatibility. Herein, we synthesized a novel star-like amphiphilic copolymer [ß-CD-P(Ir-co-OEGMA), denoted as CPIO] through atom transfer radical polymerization (ATRP) to deliver the hydrophilic anticancer drug irinotecan (Ir). The polymer could form monodisperse unimolecular micelles and had excellent stability in aqueous solution. Moreover, the reduction-responsive feature of the micelles facilitated controlled release of drug, thus achieving targeted therapy and reduced toxicity to healthy cells. The in vitro cytotoxicity assays indicated that CPIO had a notable anticancer effect against HeLa and MCF-7 tumor cells. The confocal laser scanning microscopy and flow cytometry experiments revealed that CPIO micelles could be internalized into tumor cells efficiently. Furthermore, the obtained prodrug micelles produced better efficacy compared to free Ir. Moreover, the CPIO micelles showed excellent biocompatibility in vivo after intravenous injection on a mouse model. This study demonstrated that CPIO carrier could provide a rational design of a stimuli-responsive polymeric prodrug for delivery of irinotecan.

Reduction-active polymeric prodrug micelles based on α-cyclodextrin polyrotaxanes for triggered drug release and enhanced cancer therapy.

As one of the medical polymers approved by US Food and Drug Administration (FDA), poly(ethylene glycol) has low toxicity, high stability, good biocompatibility, unique physical and chemical properties. Cyclodextrin is an ideal candidate as a drug carrier due to its special structures and characteristics. These two materials were successfully assembled through chemosynthesis in combination with the hydrophilic poly(ethylene glycol) methyl ether methacrylate (OEGMA) chain and hydrophobic polymeric camptothecin (CPT) chain by atom transfer radical polymerization (ATRP). The introduction of disulfide bond of monomer was aimed to realize reduction agent-triggered release of active CPT. The obtained amphipathic prodrug [(Denoted as PC-PCPT-b-POEGMA (PCCO)] could form nano-sized polymeric micelles, which could release more than 85% of the loaded CPT via triggered cleavage of the disulfide linker. The cellular co-localization study revealed the potential pathway of drug internalization. Moreover, the PCCO micelles showed good biocompatibility in vivo after intravenous injection on a mouse model. This new CPT-loaded prodrug system could be prepared with low cost, and showed efficient and controlled drug release and favorable biocompatibility, demonstrating a promising potential as a stimuli-responsive polymeric prodrug for future clinical applications.

Water-soluble fluorescent unimolecular micelles: ultra-small size, tunable fluorescence emission from the visible to NIR region and enhanced biocompatibility for in vitro and in vivo bioimaging.

Fluorescent unimolecular micelles (FUMs) with multicolor emission acting as fluorescent nanoagents for optical fluorescence imaging have, for the first time, been reported. The FUMs show good water-solubility, ultra-small size, and enhanced biocompatibility, which endow the FUMs with versatile applications including organelle labeling, multicolor markers and high tumor accumulation, revealing that our design can serve as a rational strategy for the development of UM-based fluorescent nanoagents for bioprocess monitoring.