Pressureless Welding of Temperature-Invariant Multifunctionality Body Based on Hydroxyl-Functionalized Boron Nitride Nanosheets and Bifunctional Monoethanolamine Cross-linker.

Bulk hexagonal boron nitride (h-BN) ceramics with structural integrity, high-temperature resistance and low expansion rate are expected for multifunctional applications in extreme conditions. However, due to its sluggish self-diffusion and intrinsic inertness, it remains a great challenge to overcome high-energy barrier for h-BN powder sintering. Herein, a cross-linking and pressureless-welding strategy is reported to produce bulk boron nitride nanosheets (BNNSs) ceramics with well-crystalized and dense B-N covalent-welding frameworks. The essence of this synthesis strategy lies in the construction of >B─O─H2C─H2C─H2N:→B< bond bridge connection structure among hydroxyl functionalized BNNSs (BNNSs-OH) using bifunctional monoethanolamine (MEA) as cross-linker through esterification and intermolecular-coordination reactions. The prepared BNNSs-interlaced ceramics have densities not less than 1.2 g cm-3, and exhibit exceptional mechanical robustness and resiliency, excellent thermomechanical stability, ultra-low linear thermal expansion coefficient of 0.06 ppm °C-1, and high thermal diffusion coefficient of 4.76 mm2 s-1 at 25 °C and 3.72 mm2 s-1 at 450 °C. This research not only reduces the free energy barrier from h-BN particles to bulk ceramics through facile multi-step physicochemical reaction, but also stimulates further exploration of multifunctional applications for bulk h-BN ceramics over a wide temperature range.

Dual Activation of Calcium Channels Using Near-Infrared Responsive Conjugated Oligomer Nanoparticles for Precise Regulation of Blood Glucose Homeostasis.

The rarity of efficient tools with spatiotemporal resolution and biocompatibility capabilities remains a major challenge for further progress and application of signaling manipulation. Herein, biomimetic conjugated oligomeric nanoparticles (CM-CONs) were developed to precisely modulate blood glucose homeostasis via the two-pronged activation of calcium channels. Under near-infrared (NIR) laser irradiation, CM-CONs efficiently generate local heat and reactive oxygen species (ROS), thereby simultaneously activating thermosensitive transient receptor potential V1 (TRPV1) and ROS-sensitive transient receptor potential A1 (TRPA1) calcium channels in small intestinal endocrine cells. The activation of the channels mediates inward calcium flow and then promotes glucagon-like peptide (GLP-1) secretion. Both in vitro and in vivo studies indicate that CM-CONs effectively regulate glucose homeostasis in diabetic model mice upon NIR light irradiation. This work develops a two-pronged attack strategy for accurately controlling blood glucose homeostasis, holding great prospects in the treatment for diabetes.

Influence of electron donor and acceptor substituents on tuning the nonlinear optical properties of zinc phthalocyanine derivatives.

Four phthalocyanine derivatives with different electron donor and acceptor substituents (B1, B2, B3, and B4) were synthesized by a solid-phase melting method. The influence of substituent type on the nonlinear optical properties of the materials was investigated in detail. In the case of similar conjugated structures, B3, which has amino electron-donor groups, presents high intramolecular charge transfer, a low energy gap (2.05 eV), and good nonlinear optical properties. Compared with B3, B4 has a larger π-conjugated structure and its energy gap is 0.04 eV smaller. Moreover, B4 has stronger reverse saturation absorption (7 × 10-12 m/W) and optical limiting performance. The four phthalocyanine derivatives exhibit third harmonic generation (THG) characteristics. Furthermore, the third harmonic strengths of B1, B2, B3, and B4 are 4 times, 9 times, 11 times, and 21 times that of SiO2, respectively. So, B4 has the best application potential in laser protection and frequency conversion.

Synthesis of Vinylene-Linked Thiopyrylium-, Pyrylium-, and Pyridinium-Based Covalent Organic Frameworks by Acid-Catalyzed Aldol Condensation.

The development of new vinylene-linked covalent organic frameworks (COFs) with special ionic structure and high stability is challenging. Herein, we report a facile, general method for constructing ionic vinylene-linked thiopyrylium-based COFs from 2,4,6-trimethylpyrylium tetrafluoroborate and other common reagents by means of acid-catalyzed Aldol condensation. Besides, pyrylium-, and pyridinium-based COFs also can be prepared from the same monomer under slightly different reaction conditions. The COFs exhibited uniform nanofibrous morphologies with excellent crystallinities, special ionic structures, well-defined nanochannels, and high specific surface areas.

Synthesis and nonlinear optical properties of polyurethane composites containing a pyrene derivative.

The pyrene derivative (PD) was synthesized with pyrene-1-carboxaldehyde and p-aminoazobenzene by a Schiff base reaction. Then the obtained PD was dispersed in polyurethane (PU) prepolymer to prepare polyurethane/pyrene derivative PU/PD materials with good transmittance. The nonlinear optical (NLO) performances of the PD and PU/PD materials were studied by the Z-scan technique under picosecond and femtosecond laser pulses. The PD has reverse saturable absorption (RSA) properties under the excitation of 532 nm 15 ps pulses, 650 and 800 nm 180 fs pulses, and a low optical limiting (OL) threshold (0.01J/c m 2). The PU/PD has a larger RSA coefficient than that of the PD under 532 nm 15 ps pulses. With the enhanced RSA, the PU/PD materials exhibit excellent OL (OL) performance. Good NLO properties, high transparency, and easy processing performances make the PU/PD an excellent choice for use in OL and laser protection fields.

Covalent organic framework wrapped by graphene oxide as an efficient sulfur host for high performance lithium-sulfur batteries.

The practical application of lithium-sulfur battery is seriously limited by the loss of active substances and the deterioration of cycle stability caused by the 'shuttle effect' of lithium polysulfides (LiPSs). In this work, graphene oxide (GO) coated covalent organic framework (COF) compound materials were synthesized as sulfur host material in spray-drying process. The polar groups on COF can efficiently adsorb LiPSs through lithiophilic interaction, which can reduce the 'shuttle effect' caused by soluble LiPSs. Besides, GO in the outer layer can wrap discrete sulfur to reduce the loss of active substances, which further improves the cycle stability of the cathode. The COF@GO/S cathode exhibits a high initial specific capacity of 848.4 mAh g-1and retains a capacity of 601.1 mAh g-1after 500 cycles at 1 C counting with a low capacity fading of 0.058% per cycle.

The Preparation of Biomineralized PIC/HA Hybrid Composites with Strain-Stiffening and the Effect on MC3T3-E1 Cells.

The development of biomimetic extracellular matrix (ECM) with fibrous structure and complex nonlinear mechanics has been attracting intensive attention over the past decades both in material science and tissue engineering. Polyisocyanopeptide (PIC) hydrogels are a class of fully synthetic materials that can mimic biogels, such as fibrin and collagen, in nearly all aspects, particularly the micron-sized gel network and the strong strain-stiffening behavior in the biological regime. Here, a biomimetic PIC/hydroxyapatite (HA) hybrid composite through an enzymatic biomineralization strategy is constructed. HA biominerals grew on PIC bundles in situ catalyzed by the embedded alkaline phosphatase (ALP), which further crosslinked the gel networks and reinforced the mechanical property of PIC hydrogels. Significantly, PIC/HA composites exhibited ultra-responsive nonlinear mechanics with higher sensitivity to mechanical stress compared with those without biomineralization. As a consequence, the presence of HA can provide cell adhesion sites for PIC gels and induce osteogenic differentiation of pre-osteoblasts by virtue of the changes in mechanical properties. With these outstanding properties, therefore, PIC/HA composites present promising prospects in bone tissue engineering as biomimetic ECM.

Nanoscale melamine-based porous organic frameworks as host material for efficient polysulfides chemisorption in lithium-sulfur batteries.

In order to improve the electrochemical capacity of lithium-sulfur batteries (LiSBs), it is necessary to introduce the porous organic frameworks with well-defined hetero atom species in cathode. In this work, porous nanomaterials with ultra-high nitrogen containing and adjustable porosity named Schiff-based networks (SNWs) were selected as potential candidate for sulfur host in LiSBs. Two SNW samples have been constructed by reacting melamine with phenyl or biphenyl dialdehydes through microwave-assisted method, respectively. The high BET surface area provided sufficient room to impregnate sulfur and mitigated volume changes during the cycling performance. Besides, the high density and homogeneous distribution of pyridinic-N and aminic-N in SNW nanoparticles can cooperatively form lithium polysulfides (LiPSs) chemisorption via enhanced Li+-N interactions to effectively suppressed the 'shuttle effect'. Attributed to its structural superiorities, SNW/S cathode demonstrates excellent electrochemical performance in LiSBs. In particular, SNW-2/S cathode delivers an excellent cyclability with a specific capacity of 620 mAh · g-1 after 500 cycles at 0.5 C, counting with a low capacity fading of 0.0508% per cycle. This work highlights the importance of rational design for effective LiPSs chemisorption and pioneers a facile strategy for developing suitable sulfur host materials towards high-performance LiSBs.

Enhanced Thermal Conductivity of Polyimide Composites Filled with Modified h-BN and Nanodiamond Hybrid Filler.

A new thermally conductive and electrically insulative polyimide were prepared by filling different amounts of hexagonal boron nitride (h-BN) particles, and the thermal conductivity of Polyimide (PI) composites were improved with the increasing h-BN content. Based on this, two methods were applied to improve thermal conductivity furtherly at limited filler loading in this paper. One is modifying the h-BN to improve interface interaction, another is fabricating a nano-micro hybrid filler with 2-D h-BN and 0-D nano-scale nanodiamond (ND) to build more effective conductive network. Both surface modification and hybrid system have a positive effect on thermal conductivity. The composites introducing 40 wt% hybrid filler (the weight ratio of ND/modified BN was 1/10) showed the highest thermal conductivity, being up to 0.98 W/(m K) (5.2 times that of PI). In addition, the composites exhibits excellent electrical insulation, thermal stability properties etc.

Functionalization of Nanodiamond with Four Kinds of Expoxies.

In this work, a simple and effective method for the covalent functionalization of nanodiamond (ND) with four epoxies has been developed. After homogenization by mixed acids and thionyl chlorides, the surface of ND was modified with triethylenetetramine (TETA) to possess amine groups, which were used as active points to react with epoxy by ring opening reaction. Four different epoxies used are bifunctional diglycidyl ether of bisphenol-A (DGEBA), trifunctional triglycidyl p-amino phenol (TGAP), tetrafunctional tetraglycidyldiamino diphenylmethane (TGDDM) and bisphenol-A novolac epoxy resin (BAEPN). FT-IR spectra revealed that the epoxy was covalently attached to the ND (ND-g-epoxy). In addition, functionalized ND particles were characterized with WAXD and UV-Vis spectra to confirm the result. The weight gains as a result of the epoxy-functionalized ND were determined by TGA analysis. The ND-g-epoxy particles were better dispersed in common organic solvents and the average diameters were characterized. The better dispersion and of the modified ND were identified from the SEM images.

Preparation of Polyimide/MWCNT Nanocomposites via Solid State Shearing Pulverization (S3P) Processing.

Polyimide/multiwall carbon nanotube (PI/MWCNT) nanocomposite films with homogeneous MWCNTs dispersion were prepared via a solid state shearing pulverization (S3P) approach. Polyimide precursor, viz., poly(amic acid) (PAA), was synthesized from 4,4'-oxydianiline (ODA) and pyromellitic dianhydride (PMDA). Then, 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA) was mixed with the PAA powder and acid functionalized MWCNTs (acid-MWCNTs) by solid state shearing pulverization (S3P) approach. Finally, PI/MWCNT nanocomposite films were prepared by thermal imidization at elevated temperatures. Using such an approach not only the MWCNTs are well-dispersed but also the mechanical and thermal properties of PI are improved. The tensile strength of PI was enhanced by 74% and the elongation at break decreased to 10.35% with 5.0 wt% acid- MWCNT loading. And the glass transition temperature of PI was increased to 341 degrees C from 303 degrees C because of the strong interfacial bonding between PI and acid-MWCNTs. The solid state shearing pulverization (S3P) approach developed in this study provides a novel method to prepare various polymer composites with desired particle dispersion.

A gene delivery system with autophagy blockade for enhanced anti-angiogenic therapy against Fusobacterium nucleatum-associated colorectal cancer.

Anti-angiogenesis has emerged a promising strategy against colorectal cancer (CRC). However, the efficacy of anti-angiogenic therapy is greatly compromised by the up-regulated autophagy levels resulting from the evolutionary resistance mechanism and the presence of Fusobacterium nucleatum (F. nucleatum) in CRC. Herein, we report a cationic polymer capable of blocking autophagic flux to deliver plasmid DNA (pDNA) encoding soluble FMS-like tyrosine kinase-1 (sFlt-1) for enhanced anti-angiogenic therapy against F. nucleatum-associated CRC. The autophagy-inhibiting cationic polymer, referred to as PNHCQ, is synthesized by conjugating hydroxychloroquine (HCQ) into 3,3'-diaminodipropylamine-pendant poly(ß-benzyl-L-aspartate) (PAsp(Nors)), which can be assembled and electrostatically interacted with sFlt-1 plasmid to form PNHCQ/sFlt-1 polyplexes. Hydrophobic HCQ modification not only boosts transfection efficiency but confers autophagy inhibition activity to the polymer. Hyaluronic acid (HA) coating is further introduced to afford PNHCQ/sFlt-1@HA for improved tumor targeting without compromising on transfection. Consequently, PNHCQ/sFlt-1@HA demonstrates significant anti-tumor efficacy in F. nucleatum-colocalized HT29 mouse xenograft model by simultaneously exerting anti-angiogenic effects through sFlt-1 expression and down-regulating autophagy levels exacerbated by F. nucleatum challenge. The combination of anti-angiogenic gene delivery and overall autophagy blockade effectively sensitizes CRC tumors to anti-angiogenesis, providing an innovative approach for enhanced anti-angiogenic therapy against F. nucleatum-resident CRC. STATEMENT OF SIGNIFICANCE: Up-regulated autophagy level within tumors is considered responsible for the impaired efficacy of clinic antiangiogenic therapy against CRC colonized with pathogenic F. nucleatum. To tackle this problem, an autophagy-inhibiting cationic polymer is developed to enable efficient intracellular delivery of plasmid DNA encoding soluble FMS-like tyrosine kinase-1 (sFlt-1) and enhance anti-angiogenic therapy against F. nucleatum-associated CRC. HA coating that can be degraded by tumor-enriching hyaluronidase is further introduced for improved tumor targeting without compromising transfection efficiency. The well-orchestrated polyplexes achieve considerable tumor accumulation, efficient in vivo transfection, and effectively reinforce the sensitivity of CRC to the sFlt-1-derived anti-angiogenic effects by significantly blocking overall autophagy flux exacerbated by F. nucleatum challenge, thus harvesting robust antitumor outcomes against F. nucleatum-resident CRC.

Engineering lauric acid-based nanodrug delivery systems for restoring chemosensitivity and improving biocompatibility of 5-FU and OxPt against Fn-associated colorectal tumor.

Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the combination chemotherapy regimen of 5-fluorouracil (5-FU) and platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy for CRC treatment in clinical practice, chemotherapy resistance caused by tumor-resided Fusobacterium nucleatum (Fn) could result in treatment failure. To enhance the efficacy and improve the biocompatibility of combination chemotherapy, we developed an antibacterial-based nanodrug delivery system for Fn-associated CRC treatment. A tumor microenvironment-activated nanomedicine 5-FU-LA@PPL was constructed by the self-assembly of chemotherapeutic drug derivatives 5-FU-LA and polymeric drug carrier PPL. PPL is prepared by conjugating lauric acid (LA) and OxPt to hyperbranched polyglycidyl ether. In principle, LA is used to selectively combat Fn, inhibit autophagy in CRC cells, restore chemosensitivity of 5-FU as well as OxPt, and consequently enhance the combination chemotherapy effects for Fn-associated drug-resistant colorectal tumor. Both in vitro and in vivo studies exhibited that the tailored nanomedicine possessed efficient antibacterial and anti-tumor activities with improved biocompatibility and reduced non-specific toxicity. Hence, this novel anti-tumor strategy has great potential in the combination chemotherapy of CRC, which suggests a clinically relevant valuable option for bacteria-associated drug-resistant cancers.

Iron-Coordinated L-Lysine-Based Nanozymes with High Peroxidase-like Activity for Sensitive Hydrogen Peroxide and Glucose Detection.

It is crucial to develop sensitive and accurate sensing strategies to detect H2O2 and glucose in biological systems. Herein, biocompatible iron-coordinated L-lysine-based hydrogen peroxide (H2O2)-mimetic enzymes (Lys-Fe-NPs) were prepared by precipitation polymerization in aqueous solution. The coordinated Fe2+ ion acted as centers of peroxidase-like enzymes of Lys-Fe-NPs, and the catalytic activity was evaluated via the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2. Therefore, a sensitive colorimetric detection sensor for H2O2 was constructed with a linear range of 1 to 200 µM and a detection limit of 0.51 µM. The same method could also be applied to highly sensitive and selective detection of glucose, with a linear range of 0.5 to 150 µM and a detection limit of 0.32 µM. In addition, an agarose-based hydrogel biosensor colorimetric was successfully implemented for visual assessment and quantitative detection of glucose. The design provided a novel platform for constructing stable and nonprotein enzyme mimics with lysine and showed great potential applications in biorelevant assays.

Zwitterionic and Hydrophilic Vinylene-Linked Covalent Organic Frameworks for Efficient Photocatalytic Hydrogen Evolution.

Developing effective synthetic strategies as well as broadening functionalities for zwitterionic materials that comprise moieties with equimolar cationic and anionic groups still remains a huge challenge. Herein, we develop two zwitterionic vinylene-linked covalent organic frameworks (Zi-VCOF-1 and Zi-VCOF-2) that are a type of novel hydrophilic material. Zi-VCOF-1 and Zi-VCOF-2 are obtained directly through the convenient Knoevenagel condensation of new sulfonic-pyridinium zwitterionic monomers with aromatic aldehyde derivatives. This is the first report on zwitterionic COFs being constructed by the bottom-up functionalization approach from predesigned zwitterionic monomers. Both Zi-VCOFs exhibit a high photocatalytic hydrogen evolution rate (HER) because of their appropriate optical property and outstanding hydrophilicity. Specifically, Zi-VCOF-1 and Zi-VCOF-2 show photocatalytic HER of 13,547 and 5057 µmol h-1 g-1, respectively. Interestingly, the photocatalytic HER of Zi-VCOF-1 is about 2.68 times of that of Zi-VCOF-2, although they differ by only one methyl group in sulfonic-pyridinium zwitterionic pairs. The photocatalytic HER of Zi-VCOF-1 is not only the highest in the vinylene-linked COFs but also outstanding among the most reported COFs. This is the first application of zwitterionic COFs for photocatalytic hydrogen evolution, which would open a new frontier in zwitterionic COFs and be helpful for the design of other photocatalytic materials.

Multi-function hollow nanorod as an efficient sulfur host accelerates sulfur redox reactions for high-performance Li-S batteries.

The "shuttle effect" of lithium polysulfides (LiPSs) leads to loss of active materials and the deterioration of cycle stability, which seriously restricts the practical progress of lithium-sulfur (Li-S) batteries. The diffusion of soluble discharge intermediate is the root cause of the above problems. Herein, we synthesized a porous organic framework material (HUT-8) based on triazine network, the polar groups above the hollow structure can not only adsorb LiPSs through electron donating effect, but also anchored cobalt (II) ions provide a large number of binding sites for the in-situ growth of CoS2. This ensured maximized exposure of catalytic centre and improve their interactions with sulfur redox species under the confinement of mesopores, which can catalytically accelerate capture/diffusion of LiPSs and precipitation/decomposition of Li2S. Based on the synergistic effect of the composite materials, the CoS2-HUT-8/S cathode maintained a capacity of 583 mAh g-1 after 500 cycles at 1 C, and a minimum capacity fading rate of 0.046% per cycle. A freestanding CoS2-HUT-8/S cathode with sulfur loading of 5.2 mg cm-2 delivered a high areal capacity of 4.01 mAh cm-2 under a lean electrolyte, which would provide great potential for the practical progress of Li-S batteries.

Effects of Europium Complex on Thermal and Photoluminescence Properties of Polyurethane-Europium Materials.

A europium complex with double bonds was synthesized with crotonic acid as the ligand and a europium ion as the center ion. Then, the obtained europium complex was added to synthesized poly(urethane-acrylate) macromonomers to prepare the bonded polyurethane-europium materials by the polymerization of the double bonds in the complex and the poly(urethane-acrylate) macromonomers. The prepared polyurethane-europium materials had high transparency, good thermal stability and good fluorescence. The storage moduli of polyurethane-europium materials are obviously higher than those of pure polyurethane. Polyurethane-europium materials exhibit bright red light with good monochromaticity. The light transmittance of the material decreases slightly with increases in the europium complex content, but the luminescence intensity gradually increases. In particular, polyurethane-europium materials possess a long luminescence lifetime, which has potential applications for optical display instruments.

NIR-II Regulation of Mitochondrial Potassium Channel with Dual-Targeted Conjugated Oligomer Nanoparticles for Efficient Cancer Theranostics In Vivo.

Cell fate can be efficiently modulated by switching ion channels. However, the precise regulation of ion channels in cells, especially in specific organelles, remains challenging. Herein, biomimetic second near-infrared (NIR-II) responsive conjugated oligomer nanoparticles with dual-targeted properties are designed and prepared to modulate the ion channels of mitochondria to selectively kill malignant cells in vivo. Upon 1060 nm laser irradiation, the mitochondria-located nanoparticles photothermally release a specific ion inhibitor of the potassium channel via a temperature-sensitive liposome, thus altering the redox balance and pathways of mitochondria. NIR-II responsive nanoparticles can effectively regulate the potassium channels of mitochondria and fully suppress tumor growth. This work provides a new modality based on the NIR-II nanoplatform to regulate ion channels in specific organelles and proposes an effective therapeutic mechanism for malignant tumors.

Mechanical Properties and Non-Isothermal Crystallization Kinetics of Polylactic Acid Modified by Polyacrylic Elastomers and Cellulose Nanocrystals.

In this paper, a polyacrylic elastomer latex with butyl acrylate (BA) as the core and methyl methacrylate (MMA) copolymerized with glycidyl methacrylate (GMA) as the shell, named poly(BA-MMA-GMA) (PBMG), was synthesized by seeded emulsion polymerization. Cellulose nanocrystal (CNC) was dispersed in the polyacrylic latex to prepare PBMG/CNC dispersions with different CNC contents. The dried product was mixed with polylactic acid (PLA) to fabricate PLA/PBMG/CNC blends. The addition of PBMG and PBMG/CNC improved the mechanical properties of the PLA matrix. Differential scanning calorimetry (DSC) was used to investigate the non-isothermal crystallization kinetics. The Avrami equation modified by the Jeziorny, Ozawa and Mo equations was used to analyze the non-isothermal crystallization kinetics of PLA and its blends. Analysis of the crystallization halftime of non-isothermal conditions indicated that the overall rate of crystallization increased significantly at 1 wt% content of CNC. This seemed to result from the increase of nucleation density and the acceleration of segment movement in the presence of the CNC component. This phenomenon was verified by polarizing microscope observation.

Near Infrared-Activatable Methylene Blue Polypeptide Codelivery of the NO Prodrug via π-π Stacking for Cascade Reactive Oxygen Species Amplification-Mediated Photodynamic Therapy.

The application of photodynamic therapy (PDT) has attracted remarkable interest in cancer treatment because of the advantages of noninvasiveness and spatiotemporal selectivity. However, the PDT efficiency is considerably limited by photosensitizer (PS) quenching and severe hypoxia in solid tumors. Herein, a kind of near infrared (NIR)-activatable methylene blue (MB) peptide nanocarrier was developed for codelivery of nitric oxide (NO) prodrug JSK, expecting a cascade of reactive oxygen species (ROS) amplification-mediated antitumor PDT. In detail, MB was conjugated to water-soluble polyethylene glycol-polylysine (PEG-PLL) through NIR-photocleavable 10-N-carbamoyl bonds, and the subsequent amphiphilic conjugates (mPEG-PLL-MB) self-assembled into nanoparticles (NPs), which allowed JSK codelivery via π-π stacking interactions. MB in quenched state in mPEG-PLL-MB/JSK NPs could be photoactivated by NIR light locoregionally in a controlled manner due to the photocleavage of carbamoyl bonds. Apart from ROS production, assembly disturbance and even disintegration of mPEG-PLL-MB/JSK occurred along with MB activation that subsequently freed JSK, which was further triggered by intracellularly overexpressed glutathione (GSH) and glutathione S-transferase (GST) to sustain the release of NO. NO then served as a hypoxia relief agent through inhibition of cellular respiration to economize O2, cooperating with MB activation and GSH depletion, which synergistically enabled a cascade of ROS amplification to augment PDT for mitochondrial apoptosis-mediated tumor inhibition in vitro and in vivo. Therefore, this pioneering strategy of cascade amplification of ROS addressed the key issues of PS inactivation, hypoxia resistance, and ROS neutralization in a three-pronged approach, which hold great promise in efficient antitumor PDT.