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.

Intracellular marriage of bicarbonate and Mn ions as "immune ion reactors" to regulate redox homeostasis and enhanced antitumor immune responses.

BACKGROUND: Different from Fe ions in Fenton reaction, Mn ions can function both as catalyst for chemodynamic therapy and immune adjuvant for antitumor immune responses. In Mn-mediated Fenton-like reaction, bicarbonate ([Formula: see text]), as the most important component to amplify therapeutic effects, must be present, however, intracellular [Formula: see text] is strictly limited because of the tight control by live cells. RESULTS: Herein, Stimuli-responsive manganese carbonate-indocyanine green complexes (MnCO3-ICG) were designed for intracellular marriage of bicarbonate and Mn ions as "immune ion reactors" to regulate intracellular redox homeostasis and antitumor immune responses. Under the tumor acidic environment, the biodegradable complex can release "ion reactors" of Mn2+ and [Formula: see text], and ICG in the cytoplasm. The suddenly increased [Formula: see text] in situ inside the cells regulate intracellular pH, and accelerate the generation of hydroxyl radicals for the oxidative stress damage of tumors cells because [Formula: see text] play a critical role to catalyze Mn-mediated Fenton-like reaction. Investigations in vitro and in vivo prove that the both CDT and phototherapy combined with Mn2+-enhanced immunotherapy effectively suppress tumor growth and realize complete tumor elimination. CONCLUSIONS: The combination therapy strategy with the help of novel immune adjuvants would produce an enhanced immune response, and be used for the treatment of deep tumors in situ.

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.

Hydrothermal liquefaction of Chlorella pyrenoidosa and effect of emulsification on upgrading the bio-oil.

This work studied the hydrothermal liquefaction of Chlorella pyrenoidosa and effect of emulsification on upgrading the bio-oil. The fuel properties and storage stability characteristics of emulsion fuels were explored. The combustion characteristic analysis showed that the ignition temperatures of emulsion fuels (139.6-151.3 °C) were lower than that of bio-oil (176.9 °C). Besides, emulsion fuels had higher comprehensive combustion indexes (7.24-14.08 × 10-6 × min-2 × C-3) than bio-oil (1.51 × 10-6 × min-2 × C-3), indicating that emulsion fuels had better combustion performance. The kinetic analysis showed that emulsification could effectively reduce the activation energy, resulting in less energy input for combustion. Based on chemical composition evolution during the storage process, a possible stability mechanism was proposed. The storage stability analysis indicated that the diesel-solvable fractions in bio-oil had better stability. Overall, this work provides a feasible way for bio-oil upgrading through emulsification. In addition, a better understanding of the stability property of emulsion fuel was provided.

Investigation of Mannich reaction during co-liquefaction of microalgae and sweet potato waste: Combustion performance of bio-oil and bio-char.

Microalgae (MA) was co-liquefied with sweet potato waste (SPW) to improve bio-oil and bio-char qualities via Mannich reaction. The influence of Mannich reaction on combustion performances of bio-oil and bio-char were investigated. Results suggested that the addition of SPW decrease the ignition temperature of bio-oil from 186.6 °C to 165.0 °C. In addition, the denitrification effect of Mannich reaction can decrease the HCN and NO emission of bio-oil, contributing to reducing pollutant emission. As for bio-char, Mannich reaction improved the combustible material content in bio-char, which decreased the risk of slagging problem. The comprehensive combustion indexes of bio-oil (1.23 × 10-6 × min-2×°C-3) and bio-char (4.79 × 10-8 × min-2×°C-3) from co-liquefaction were higher than those from liquefaction of MA (0.91 × 10-6 × min-2×°C-3 for bio-oil and 1.24 × 10-8 × min-2×°C-3 for bio-char), indicating that the combustion performance was promoted by adding SPW. Overall, Mannich reaction can be applied to improve the combustion performance of bio-oil and bio-char.

Comparison of catalytic effect on upgrading bio-oil derived from co-pyrolysis of water hyacinth and scrap tire over multilamellar MFI nanosheets and HZSM-5.

Catalytic co-pyrolysis of water hyacinth and scrap tire experiments were performed to evaluate the feasibility of improving the monocyclic aromatic hydrocarbons production. The production of monocyclic aromatic hydrocarbons increased from 5.31% (sole pyrolysis of water hyacinth) to 13.11% (co-pyrolysis with scrap tire). With use of zeolites, the highest production of monocyclic aromatic hydrocarbons can reach up to 69.18%. Comprehensive comparison on catalytic effects of HZSM-5 and multilamellar MFI nanosheets were provided. With the material to multilamellar MFI nanosheets ratios changes from 2:1 to 1:4, the production of monocyclic aromatic hydrocarbons increases significantly from 37.15-69.18%. The average production of monocyclic aromatic hydrocarbons produced by using multilamellar MFI nanosheets were 12.07% higher than that using HZSM-5, indicating the better performance of multilamellar MFI nanosheets in producing monocyclic aromatic hydrocarbons. This work provided a reference for the reuse of water hyacinth and scrap tire over multilamellar MFI nanosheets in energy field.

Development of a novel truncated deguelin derivative possessing nitric oxide donor as a potential anti-lung cancer agent.

Lung cancer is the leading cause of cancer death in the world. Natural product deguelin and its truncated analogs have been reported to be potential therapeutic agents for lung cancer. In order to improve the potency, a novel truncated deguelin derivative (4) possessing nitric oxide (NO) donor was designed and synthesized. The biological evaluation showed that hybrid 4 exerted potent activity with an IC50 value of 0.41 µM in H1299 cells. Mechanism studies showed that it arrested the cell cycle at G2/M phase and suppressed Hsp90 function. In addition, hybrid 4 demonstrated potent inhibitory activity on the migration and invasion of lung cancer cells. Together, the promising results warrant further development of hybrid 4 as a potential anticancer agent for the treatment of lung cancer.

Tumor-Microenvironment-Activatable Nanoreactor Based on a Polyprodrug for Multimodal-Imaging-Medicated Enhanced Cancer Chemo/Phototherapy.

Anticancer nanomedicine-based multimodal imaging and synergistic therapy hold great promise in cancer diagnosis and therapy owing to their abilities to improve therapeutic efficiency and reduce unnecessary side effects, producing promising clinical prospects. Herein, we integrated chemotherapeutic drug camptothecin (CPT) and near-infrared-absorbing new indocyanine green (IR820) into a single system by charge interaction and obtained a tumor-microenvironment-activatable PCPTSS/IR820 nanoreactor to perform thermal/fluorescence/photoacoustic-imaging-guided chemotherapy and photothermal therapy simultaneously. Specifically, the generated PCPTSS/IR820 showed an excellent therapeutic agent loading content and size stability, and the trials in vitro and in vivo suggested that the smart PCPTSS/IR820 could deeply permeate into tumor tissues due to its suitable micellar size. Upon near-infrared laser irradiation, the nanoreactor further produced a terrific synergism of chemo-photo treatment for cancer therapy. Therefore, the PCPTSS/IR820 polyprodrug-based nanoreactor holds outstanding promise for multimodal imaging and combined dual therapy.

Methotrexate-based amphiphilic prodrug nanoaggregates for co-administration of multiple therapeutics and synergistic cancer therapy.

The goal of nanomedicine is to seek strategies that are more efficient to address various limitations and challenges faced by conventional medicines, including lack of target specificity, poor bioavailability, premature degradability, and undesired side effects. Self-assembling drug amphiphiles represent a prospective nanomedicine for cancer therapy owing to their favorable route of administration and therapeutic efficiency compared with pristine drug counterparts. In this work, we report a class of self-deliverable prodrug amphiphiles consisting of the hydrophilic drug methotrexate (MTX) and the hydrophobic anticancer drugs camptothecin (CPT) and doxorubicin (DOX) for targeted and combinational chemotherapy. The disulfide bond and hydrazone bond, which are subject to stimuli-triggered bond cleavage, were introduced to link these therapeutic agents and form two prodrug amphiphiles, named as MTX-CPT and MTX-DOX, respectively, which could self-assemble into stable prodrug nanoaggregates (NAs) in aqueous media. MTX molecules in the prodrug NAs facilitated NA uptake into tumor cells with high expression of folic acid receptors (FRs). This systemic study provided clear evidence of the synergistic therapeutic effect by co-administrating dual prodrug NAs on various tumor cells in vitro and a xenograft tumor model in vivo. The obtained prodrug amphiphiles provide an efficient strategy for the design of multifunctional drug delivery systems and elaborate therapeutic nanoplatforms for cancer chemotherapy. STATEMENT OF SIGNIFICANCE: This work presents two kinds of prodrug amphiphiles that are carrier free and integrate targeted drug delivery, stimuli-triggered drug release, synergistic therapy, and theranostic function into a single system. Reduction/acid active prodrug amphiphiles can self-assemble into micellar nanoaggregates (NAs) at a very low critical aggregation concentration. These NAs exhibit superior stability in physiological environment and disassemble in the presence of tumor cells expressing folic acid receptors or the high glutathione or in low pH tumoral endosomal environment. The induced disassembly of prodrug NAs can "switch on" the inherent fluorescence of the internalized camptothecin or doxorubicin for the detection of tumor cells. Compared to a single type of prodrug NA, co-administration of dual prodrug combination can produce an evident synergistic therapeutic effect against various tumor cells in vitro and inhibit xenograft tumor growth in vivo. The methotrexate-based prodrug amphiphiles may provide a potential strategy for developing multifunctional nanoplatforms and delivery of multiple therapeutics in chemotherapy.