Modulation of Heterotypic and Homotypic Interactions to Visualize the Evolution of Organic Aggregates in a Fluorescence Turn-on Manner.

The abnormal evolution of membrane-less organelles into amyloid fibrils is a causative factor in many neurodegenerative diseases. Fundamental research on evolving organic aggregates is thus instructive for understanding the root causes of these diseases. In-situ monitoring of evolving molecular aggregates with built-in fluorescence properties is a reliable approach to reflect their subtle structural variation. To increase the sensitivity of real-time monitoring, we presented organic aggregates assembled by TPAN-2MeO, which is a triphenyl acrylonitrile derivative. TPAN-2MeO showed a morphological evolution with distinct turn-on emission. Upon rapid nanoaggregation, it formed non-emissive spherical aggregates in the kinetically metastable state. Experimental and simulation results revealed that the weak homotypic interactions between the TPAN-2MeO molecules liberated their molecular motion for efficient non-radiative decay, and the strong heterotypic interactions between TPAN-2MeO and water stabilized the molecular geometry favorable for the non-fluorescent state. After ultrasonication, the decreased heterotypic interactions and increased homotypic interactions acted synergistically to allow access to the emissive thermodynamic equilibrium state with a decent photoluminescence quantum yield (PLQY). The spherical aggregates were eventually transformed into micrometer-sized blocklike particles. Under mechanical stirring, the co-assembly of TPAN-2MeO and Pluronic F-127 formed uniform fluorescent platelets, inducing a significant enhancement in PLQY. These results decipher the stimuli-triggered structural variation of organic aggregates with concurrent sensitive fluorescence response and pave the way for a deep understanding of the evolutionary events of biogenic aggregates.

BF2-Bridged Azafulvene Dimer-Based 1064 nm Laser-Driven Superior Photothermal Agent for Deep-Seated Tumor Therapy.

Small organic photothermal reagents (PTAs) with absorption bands located in the second near-infrared (NIR-II, 1000-1700 nm) window are highly desirable for effectively combating deep-seated tumors. However, the rarely reported NIR-II absorbing PTAs still suffer from a low molar extinction coefficient (MEC, ε), inadequate chemostability and photostability, as well as the high light power density required during the therapeutic process. Herein, we developed a series of boron difluoride bridged azafulvene dimer acceptor-integrated small organic PTAs. The B-N coordination bonds in the π-conjugated azafulvene dimer backbone endow it the strong electron-withdrawing ability, facilitating the vigorous donor-acceptor-donor (D-A-D) structure PTAs with NIR-II absorption. Notably, the PTAs namely OTTBF shows high MEC (7.21× 104 M-1 cm-1), ultrahigh chemo- and photo-stability. After encapsulated into water-dispersible nanoparticles, OTTBF NPs can achieve remarkable photothermal conversion effect under 1064 nm irradiation with a light density as low as 0.7 W cm-2, which is the lowest reported NIR-II light power used in PTT process as we know. Furthermore, OTTBF NPs have been successfully applied for in vitro and in vivo deep-seated cancer treatments under 1064 nm laser. This study provides an insight into the future exploration of versatile D-A-D structured NIR-II absorption organic PTAs for biomedical applications.

More Is Better: Dual-Acceptor Engineering for Constructing Second Near-Infrared Aggregation-Induced Emission Luminogens to Boost Multimodal Phototheranostics.

The manipulation of electron donor/acceptor (D/A) shows an endless impetus for innovating optical materials. Currently, there is booming development in electron donor design, while research on electron acceptor engineering has received limited attention. Inspired by the philosophical idea of "more is different", two systems with D'-D-A-D-D' (1A system) and D'-D-A-A-D-D' (2A system) structures based on acceptor engineering were designed and studied. It was demonstrated that the 1A system presented a weak aggregation-induced emission (AIE) to aggregation-caused quenching (ACQ) phenomenon, along with the increased acceptor electrophilicity and planarity. In sharp contrast, the 2A system with one more acceptor exhibited an opposite ACQ-to-AIE transformation. Interestingly, the fluorophore with a more electron-deficient A-A moiety in the 2A system displayed superior AIE activity. More importantly, all compounds in the 2A system showed significantly higher molar absorptivity (ε) in comparison to their counterparts in the 1A system. Thanks to the highest ε, near-infrared-II (NIR-II, 1000-1700 nm) emission, desirable AIE property, favorable reactive oxygen species (ROS) generation, and high photothermal conversion efficiency, a representative member of the 2A system handily performed in fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal collaborative therapy for efficient tumor elimination. Meanwhile, the NIR-II fluorescence imaging of blood vessels and lymph nodes in living mice was also accomplished. This study provides the first evidence that the dual-connected acceptor tactic could be a new molecular design direction for the AIE effect, resulting in high ε, aggregation-intensified NIR-II fluorescence emission, and improved ROS and heat generation capacities of phototheranostic agents.

A Photoactivatable Luminescent Motif through Ring-Flipping Isomerization for Multiple Photopatterning.

Photoactivatable luminescent materials have garnered enormous attention in the field of intelligent responsive materials, yet their design and applications remain challenging due to the limited variety of photoactivatable motifs. In the work described herein, we discovered a new photoactivatable luminescent motif that underwent ring-flipping isomerization under UV irradiation. The emission of this motif exhibited a rapid transformation from dark yellow to bright green, accompanied by a significant enhancement of quantum yield from 1.9% to 34.2%. Experimental and theoretical studies revealed that the effective intramolecular motion (EIM) was crucial to the distinct luminescence performance between two isomers. In addition, polymers containing this motif were achieved through a one-pot alkyne polymerization, exhibiting both photofluorochromic and photo-cross-linking properties. Furthermore, multiple types of photopatterning, including luminescent encryption, fluorescent grayscale imaging, and high-resolution photolithographic patterns, were realized. This work developed a new photoactivatable luminescent motif and demonstrated its potential applications in both small molecules and macromolecules, which will help in the future design of photoactivatable luminescent materials.

Sulfone-Modified Covalent Organic Frameworks Enabling Efficient Photocatalytic Hydrogen Peroxide Generation via One-Step Two-Electron O2 Reduction.

Photocatalytic oxygen reduction reaction (ORR) offers a promising hydrogen peroxide (H2 O2 ) synthetic strategy, especially the one-step two-electron (2e- ) ORR route holds great potential in achieving highly efficient and selectivity. However, efficient one-step 2e- ORR is rarely harvested and the underlying mechanism for regulating the ORR pathways remains greatly obscure. Here, by loading sulfone units into covalent organic frameworks (FS-COFs), we present an efficient photocatalyst for H2 O2 generation via one-step 2e- ORR from pure water and air. Under visible light irradiation, FS-COFs exert a superb H2 O2 yield of 3904.2 µmol h-1 g-1 , outperforming most reported metal-free catalysts under similar conditions. Experimental and theoretical investigation reveals that the sulfone units accelerate the separation of photoinduced electron-hole (e- -h+ ) pairs, enhance the protonation of COFs, and promote O2 adsorption in the Yeager-type, which jointly alters the reaction process from two-step 2e- ORR to the one-step one, thereby achieving efficient H2 O2 generation with high selectivity.

Site Engineering of Covalent Organic Frameworks for Regulating Peroxymonosulfate Activation to Generate Singlet Oxygen with 100 % Selectivity.

Singlet oxygen (1 O2 ) is an excellent reactive oxygen species (ROSs) for the selective conversion of organic matter, especially in advanced oxidation processes (AOPs). However, due to the huge dilemma in synthesizing single-site type catalysts, the control and regulation of 1 O2 generation in AOPs is still challenging and the underlying mechanism remains largely obscure. Here, taking advantage of the well-defined and flexibly tunable sites of covalent organic frameworks (COFs), we report the first achievement in precisely regulating ROSs generation in peroxymonosulfate (PMS)-based AOPs by site engineering of COFs. Remarkably, COFs with bipyridine units (BPY-COFs) facilitate PMS activation via a nonradical pathway with 100 % 1 O2 , whereas biphenyl-based COFs (BPD-COFs) with almost identical structures activate PMS to produce radicals (⋅OH and SO4 .- ). The BPY-COFs/PMS system delivers boosted performance for selective degradation of target pollutants from water, which is ca. 9.4 times that of its BPD-COFs counterpart, surpassing most reported PMS-based AOPs systems. Mechanism analysis indicated that highly electronegative pyridine-N atoms on BPY-COFs provide extra sites to adsorb the terminal H atoms of PMS, resulting in simultaneous adsorption of O and H atoms of PMS on one pyridine ring, which facilitates the cleavage of its S-O bond to generate 1 O2 .

Rational Design of NIR-II AIEgens with Ultrahigh Quantum Yields for Photo- and Chemiluminescence Imaging.

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) using small-molecule dyes has high potential for clinical use. However, many NIR-II dyes suffer from the emission quenching effect and extremely low quantum yields (QYs) in the practical usage forms. The AIE strategy has been successfully utilized to develop NIR-II dyes with donor-acceptor (D-A) structures with acceptable QYs in the aggregate state, but there is still large room for QY improvement. Here, we rationally designed a NIR-II emissive dye named TPE-BBT and its derivative (TPEO-BBT) by changing the electron-donating triphenylamine unit to tetraphenylethylene (TPE). Their nanoparticles exhibited ultrahigh relative QYs of 31.5% and 23.9% in water, respectively. By using an integrating sphere, the absolute QY of TPE-BBT nanoparticles was measured to be 1.8% in water. Its crystals showed an absolute QY of 10.4%, which is the highest value among organic small molecules reported so far. The optimized D-A interaction and the higher rigidity of TPE-BBT in the aggregate state are believed to be the two key factors for its ultrahigh QY. Finally, we utilized TPE-BBT for NIR-II photoluminescence (PL) and chemiluminescence (CL) bioimaging through successive CL resonance energy transfer and Förster resonance energy transfer processes. The ultrahigh QY of TPE-BBT realized an excellent PL imaging quality in mouse blood vessels and an excellent CL imaging quality in the local arthrosis inflammation in mice with a high signal-to-background ratio of 130. Thus, the design strategy presented here brings new possibilities for the development of bright NIR-II dyes and NIR-II bioimaging technologies.

Interfacial Interactions within Amyloid Protein Corona Based on 2D MoS2 Nanosheets.

The interfacial interaction within the amyloid protein corona based on MoS2 nanomaterial is crucial, both for understanding the biological effects of MoS2 nanomaterial and the evolution of amyloid diseases. The specific nano-bio interface phenomenon of human islet amyloid peptide (hIAPP) and MoS2 nanosheet was investigated by using theoretical and experimental methods. The MoS2 nanosheet enables the attraction of hIAPP monomer, dimer, and oligomer on its surface through van der Waals forces. Especially, the means of interaction between two hIAPP peptides might be changed by MoS2 nanosheet. In addition, it is interesting to find that the hIAPP oligomer can stably interact with the MoS2 nanosheet in one unique "standing" binding mode with an entire exposed ß-sheet surface. All the interaction modes on the surface of MoS2 nanosheet can be the essence of amyloid protein corona that may provide the venue to facilitate the fibrillation of hIAPP proteins. Further, it was verified experimentally that MoS2 nanosheets could accelerate the fibrillation of hIAPP at a certain concentration mainly based on the newly formed nano-bio interface. In general, our results provide insight into the molecular interaction mechanism of the nano-bio interface within the amyloid protein corona, and shed light on the pathway of amyloid protein aggregation that is related to the evolution of amyloid diseases.

Electric Field Effect on Inhibiting the Co-fibrillation of Amyloid Peptides by Modulating the Aggregation Pathway.

With the revelation of the close link between Alzheimer's disease (AD) and type II diabetes (T2D) and the possible assembly of multiple amyloid peptides therein, it is critical to understand and regulate the co-fibrillation pathway between related amyloid peptides. Here, we show experimentally and theoretically that electric field (EF) inhibited hybrid amyloid fibrillation of ß-amyloid peptide (Aß) and human islet amyloid peptide (hIAPP) by modulating the hetero-aggregation pathway. Experimental results confirm that the ß-sheet secondary structure of amyloid peptides would be disrupted under small static EF and accompanied by transforming fibril aggregates into amorphous particles in vitro. Molecular dynamics simulations further demonstrate that even with the transformation of the secondary structure from ß-sheet to random coil, the strong interaction between Aß and hIAPP peptides would remain largely unaffected under the small static EF, leading to the formation of amorphous nanoparticles observed in the experiments. This inhibitory effect of EF on the co-fibrillation of multiple amyloid peptides might contribute to reducing the mutual deterioration of different degenerative diseases and show great potential for the noninvasive treatment of amyloid-related diseases.

Spontaneous desorption of protein from self-assembled monolayer (SAM)-coated gold nanoparticles induced by high temperature.

The nonspecific binding of proteins with nanomaterials (NMs) is a dynamic reversible process including both protein adsorption and desorption parts, which is crucial for controlled release of protein drug loaded by nanocarriers. The nonspecific binding of proteins is susceptible to high temperature, whereas its underlying mechanism still remains elusive. Here, the binding behavior of human serum albumin (HSA) with an amino-terminated self-assembled monolayer (SAM)-coated gold (111) surface was investigated by using molecular dynamics (MD) simulations. HSA binds to the SAM surface through salt bridges at 300 K. As the temperature increases to 350 K, HSA maintains its native structure, while the salt bridges largely diminish owing to the considerable lateral diffusion of HSA on the SAM. Moreover, the interfacial water located between HSA and the SAM gets increased and prevents the reformation of the salt bridges of HSA with the SAM, which reduces the binding affinity of HSA. And HSA eventually desorbs from the SAM. The depiction of thermally induced spontaneous protein desorption enriches our understanding of reversible binding behavior of protein with NMs, and may provide new insights into the controlled release of protein drugs delivered by using nanocarriers under the regulation of high temperature.

Distinct lipid membrane interaction and uptake of differentially charged nanoplastics in bacteria.

BACKGROUND: Nanoplastics have been recently found widely distributed in our natural environment where ubiquitously bacteria are major participants in various material cycles. Understanding how nanoplastics interact with bacterial cell membrane is critical to grasp their uptake processes as well as to analyze their associated risks in ecosystems and human microflora. However, little is known about the detailed interaction of differentially charged nanoplastics with bacteria. The present work experimentally and theoretically demonstrated that nanoplastics enter into bacteria depending on the surface charges and cell envelope structural features, and proved the shielding role of membrane lipids against nanoplastics. RESULTS: Positively charged polystyrene nanoplastics (PS-NH2, 80 nm) can efficiently translocate across cell membranes, while negatively charged PS (PS-COOH) and neutral PS show almost no or much less efficacy in translocation. Molecular dynamics simulations revealed that the PS-NH2 displayed more favourable electrostatic interactions with bacterial membranes and was subjected to internalisation through membrane penetration. The positively charged nanoplastics destroy cell envelope of Gram-positive B. subtilis by forming membrane pore, while enter into the Gram-negative E. coli with a relatively intact envelope. The accumulated positively charged nanoplastics conveyed more cell stress by inducing a higher level of reactive oxygen species (ROS). However, the subsequently released membrane lipid-coated nanoplastics were nearly nontoxic to cells, and like wise, stealthy bacteria wrapped up with artifical lipid layers became less sensitive to the positively charged nanoplastics, thereby illustrating that the membrane lipid can shield the strong interaction between the positively charged nanoplastics and cells. CONCLUSIONS: Our findings elucidated the molecular mechanism of nanoplastics' interaction and accumulation within bacteria, and implied the shielding and internalization effect of membrane lipid on toxic nanoplastics could promote bacteria for potential plastic bioremediation.

Inverse Boltzmann Iterative Multi-Scale Molecular Dynamics Study between Carbon Nanotubes and Amino Acids.

Our work uses Iterative Boltzmann Inversion (IBI) to study the coarse-grained interaction between 20 amino acids and the representative carbon nanotube CNT55L3. IBI is a multi-scale simulation method that has attracted the attention of many researchers in recent years. It can effectively modify the coarse-grained model derived from the Potential of Mean Force (PMF). IBI is based on the distribution result obtained by All-Atom molecular dynamics simulation; that is, the target distribution function and the PMF potential energy are extracted, and then, the initial potential energy extracted by the PMF is used to perform simulation iterations using IBI. Our research results have been through more than 100 iterations, and finally, the distribution obtained by coarse-grained molecular simulation (CGMD) can effectively overlap with the results of all-atom molecular dynamics simulation (AAMD). In addition, our work lays the foundation for the study of force fields for the simulation of the coarse-graining of super-large proteins and other important nanoparticles.

An Overlooked Natural Hydrogen Evolution Pathway: Ni2+ Boosting H2 O Reduction by Fe(OH)2 Oxidation during Low-Temperature Serpentinization.

Natural hydrogen (H2 ) has gained considerable attentions as a renewable energy resource to mitigate the globally increasing environmental concerns. Low-temperature serpentinization (<200 °C) as a typical water-rock reaction is a major source of the natural H2 . However, the reaction mechanism and the controlling step to product H2 remained unclear, which hinders the further utilization of natural H2 . Herein, we demonstrated that the H2 production rate could be determined by the Fe(OH)2 oxidation during low-temperature serpentinization. Moreover, the co-existence of Ni2+ could largely enhance the H2 production kinetics. With the addition of only 1 % Ni2+ , the H2 production rate was remarkably enhanced by about two orders of magnitude at 90 °C. D2 O isotopic experiment and theoretical calculations revealed that the enhanced H2 production kinetics could be attributed to the catalytic role of Ni2+ to promote the reduction of H2 O.

Rational Design of FeNi Bimetal Modified Covalent Organic Frameworks for Photoconversion of Anthropogenic CO2 into Widely Tunable Syngas.

Direct photoconversion of low-concentration CO2 into a widely tunable syngas (i.e., CO/H2 mixture) provides a feasible outlet for the high value-added utilization of anthropogenic CO2 . However, in the low-concentration CO2 photoreduction system, it remains a huge challenge to screen appropriate catalysts for efficient CO and H2 production, respectively, and provide a facile parameter to tune the CO/H2 ratio in a wide range. Herein, by engineering the metal sites on the covalent organic frameworks matrix, low-concentration CO2 can be efficiently photoconverted into tunable syngas, whose CO/H2 ratio (1:19-9:1) is obviously wider than reported systems. Experiments and density functional theory calculations indicate that Fe sites serve as the H2 evolution sites due to the much stronger binding affinity to H2 O, while Ni sites act as the CO production sites for the higher affinity to CO2 . Notably, the widely tunable syngas can also be produced over other Fe/Ni-based bimetal catalysts, regardless of their structures and supporting materials, confirming the significant role of the metal sites in regulating the selectivity of CO2 photoreduction and providing a modular design strategy for syngas production.

Dynamic behaviors of interfacial water on the self-assembly monolayer (SAM) heterogeneous surface.

Dynamic behaviors of water molecules near the surface with mixed hydrophobic and hydrophilic areas are studied by molecular dynamics simulation. More specifically, the diffusion coefficient and hydrogen bond lifetime of interfacial water on the self-assembly monolayer composed of hydrophobic and hydrophilic groups and their dependence on the mixing ratio are studied. The diffusion dramatically slows down, and the hydrogen bond lifetime considerably increases when a few hydrophilic groups are added to the hydrophobic surface. When the percentage of hydrophilic groups increases to 25%, the behavior of interfacial water is similar to the case of the pure hydrophilic surface. The sensitivity to the hydrophilic group can be attributed to the fact that the grafted hydrophilic groups can not only retard the directly bound water molecules but also affect indirectly bound water by stabilizing hydrogen bonds among interfacial water molecules.

Effective Extraction of Cr(VI) from Hazardous Gypsum Sludge via Controlling the Phase Transformation and Chromium Species.

Through controlling the phase transformation and chromium species under hydrothermal condition, the Cr(VI) was extracted fully from hazardous Cr(VI)-containing gypsum sludge, with a very high efficiency of more than 99.5%. Scanning transmission electron microscopy, X-ray absorption fine structure, and density functional theory calculation results revealed that the dissolution-recrystallization of CaSO4·2H2O into CaSO4 was the key factor to fully release the encapsulated Cr(VI). Moreover, the mineralizer (persulfate salt) provided H+ and SO42- ions, the former made an acidic condition to transform the released CrO42- into the specie (Cr2O72-) with less similarity to SO42-, which further prevented the recombination of the released Cr(VI) with gypsum; and the latter was essential to accelerate crystal growth of calcium sulfate so as to enhance Cr(VI) extraction. This work would provide an instructive guidance to fully extract heavy metals from hazardous solid wastes via the control of crystal transformation and the pollutant species.

Enhanced Adsorption of p-Arsanilic Acid from Water by Amine-Modified UiO-67 as Examined Using Extended X-ray Absorption Fine Structure, X-ray Photoelectron Spectroscopy, and Density Functional Theory Calculations.

p-Arsanilic acid ( p-ASA) is an emerging organoarsenic pollutant comprising both inorganic and organic moieties. For the efficient removal of p-ASA, adsorbents with high adsorption affinity are urgently needed. Herein, amine-modified UiO-67 (UiO-67-NH2) metal-organic frameworks (MOFs) were synthesized, and their adsorption affinities toward p-ASA were 2 times higher than that of the pristine UiO-67. Extended X-ray absorption fine structure (EXAFS), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculation results revealed adsorption through a combination of As-O-Zr coordination, hydrogen bonding, and π-π stacking, among which As-O-Zr coordination was the dominant force. Amine groups played a significant role in enhancing the adsorption affinity through strengthening the As-O-Zr coordination and π-π stacking, as well as forming new adsorption sites via hydrogen bonding. UiO-67-NH2s could remove p-ASA at low concentrations (<5 mg L-1) in simulated natural and wastewaters to an arsenic level lower than that of the drinking water standard of World Health Organization (WHO) and the surface water standard of China, respectively. This work provided an emerging and promising method to increase the adsorption affinity of MOFs toward pollutants containing both organic and inorganic moieties, via modifying functional groups based on the pollutant structure to achieve synergistic adsorption effect.

Nickel Metal-Organic Framework Monolayers for Photoreduction of Diluted CO2 : Metal-Node-Dependent Activity and Selectivity.

Photocatalytic conversion of diluted CO2 into solar fuel is highly appealing yet still in its infancy. Herein, we demonstrate the metal-node-dependent performance for photoreduction of diluted CO2 by constructing Ni metal-organic framework (MOF) monolayers (Ni MOLs). In diluted CO2 (10 %), Ni MOLs exhibit a highest apparent quantum yield of 1.96 % with a CO selectivity of 96.8 %, which not only exceeds reported systems in diluted CO2 but also is superior to most catalysts in pure CO2 . Whereas isostructural Co MOLs is almost inactive in diluted CO2 , indicating the performance is dependent on the metal nodes. Experimental and theoretical investigations show that strong CO2 binding affinity of Ni MOLs is the crucial factor, which stabilizes the Ni-CO2 adducts and facilitates CO2 -to-CO conversion.

The impacts of surface polarity on the solubility of nanoparticle.

In order to study the dependence of water solubility and hydration behavior of nanoparticles on their surface polarity, we designed polar nanoparticles with varying surface polarity by assigning atomic partial charge to the surface of C60. The water solubility of the nanoparticle is enhanced by several orders of magnitude after the introduction of surface polarity. Nevertheless, when the atomic partial charge grows beyond a certain value (qM), the solubility continuously decreases to the level of nonpolar nanoparticle. It should be noted that such qM is comparable with atomic partial charge of a variety of functional groups. The hydration behaviors of nanoparticles were then studied to investigate the non-monotonic dependence of solubility on the surface polarity. The interaction between the polar nanoparticle and the hydration water is stronger than the nonpolar counterpart, which should facilitate the dissolution of the nanoparticles. On the other hand, the surface polarity also reduces the interaction of hydration water with the other water molecules and enhances the interaction between the nanoparticles which may hinder their dispersion. Besides, the introduction of surface polarity disturbs and even rearranges the hydration structure of nonpolar nanoparticle. Interestingly, the polar nanoparticle with less ordered hydration structure tends to have higher water solubility.

Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy.

Ultrahigh dose-rate (FLASH) radiotherapy is an emerging technology with excellent therapeutic effects and low biological toxicity. However, tumor recurrence largely impede the effectiveness of FLASH therapy. Overcoming tumor recurrence is crucial for practical FLASH applications. Here, we prepared an agarose-based thermosensitive hydrogel containing a mild photothermal agent (TPE-BBT) and a glutaminase inhibitor (CB-839). Within nanoparticles, TPE-BBT exhibits aggregation-induced emission peaked at 900 nm, while the unrestricted molecular motions endow TPE-BBT with a mild photothermy generation ability. The balanced photothermal effect and photoluminescence are ideal for phototheranostics. Upon 660-nm laser irradiation, the temperature-rising effect softens and hydrolyzes the hydrogel to release TPE-BBT and CB-839 into the tumor site for concurrent mild photothermal therapy and chemotherapy, jointly inhibiting homologous recombination repair of DNA. The enhanced FLASH radiotherapy efficiently kills the tumor tissue without recurrence and obvious systematic toxicity. This work deciphers the unrestricted molecular motions in bright organic fluorophores as a source of photothermy, and provides novel recurrence-resistant radiotherapy without adverse side effects.