Programmable Singlet Oxygen Battery for Automated Photodynamic Therapy Enabled by Pyridone-Pyridine Tautomer Engineering.

The efficacy of photodynamic therapy is hindered by the hypoxic environment in tumors and limited light penetration depth. The singlet oxygen battery (SOB) has emerged as a promising solution, enabling oxygen- and light-independent 1O2 release. However, conventional SOB systems typically exhibit an "always-ON" 1O2 release, leading to potential 1O2 leakage before and after treatment. This not only compromises therapeutic outcomes but also raises substantial biosafety concerns. In this work, we introduce a programmable singlet oxygen battery, engineered to address all the issues discussed above. The concept is illustrated through the development of a tumor-microenvironment-responsive pyridone-pyridine switch, PyAce, which exists in two tautomeric forms: PyAce-0 (pyridine) and PyAce (pyridone) with different 1O2 storage half-lives. In its native state, PyAce remains in the pyridone form, capable of storing 1O2 (t1/2 = 18.5 h). Upon reaching the tumor microenvironment, PyAce is switched to the pyridine form, facilitating rapid and thorough 1O2 release (t1/2 = 16 min), followed by quenched 1O2 release post-therapy. This mechanism ensures suppressed 1O2 production pre- and post-therapy with selective and rapid 1O2 release at the tumor site, maximizing therapeutic efficacy while minimizing side effects. The achieved "OFF-ON-OFF" 1O2 therapy showed high spatiotemporal selectivity and was independent of the oxygen supply and light illumination.

Unraveling the Transformation from Type-II to Z-Scheme in Perovskite-Based Heterostructures for Enhanced Photocatalytic CO2 Reduction.

The ability to create perovskite-based heterostructures with desirable charge transfer characteristics represents an important endeavor to render a set of perovskite materials and devices with tunable optoelectronic properties. However, due to similar material selection and band alignment in type-II and Z-scheme heterostructures, it remains challenging to obtain perovskite-based heterostructures with a favorable electron transfer pathway for photocatalysis. Herein, we report a robust tailoring of effective charge transfer pathway in perovskite-based heterostructures via a type-II to Z-scheme transformation for highly efficient and selective photocatalytic CO2 reduction. Specifically, CsPbBr3/TiO2 and CsPbBr3/Au/TiO2 heterostructures are synthesized and then investigated by ultrafast spectroscopy. Moreover, taking CsPbBr3/TiO2 and CsPbBr3/Au/TiO2 as examples, operando experiments and theoretical calculations confirm that the type-II heterostructure could be readily transformed into a Z-scheme heterostructure through establishing a low-resistance Ohmic contact, which indicates that a fast electron transfer pathway is crucial in Z-scheme construction, as further demonstrated by CsPbBr3/Ag/TiO2 and CsPbBr3/MoS2 heterostructures. In contrast to pristine CsPbBr3 and CsPbBr3/TiO2, the CsPbBr3/Au/TiO2 heterostructure exhibits 5.4- and 3.0-fold enhancement of electron consumption rate in photocatalytic CO2 reduction. DFT calculations and in situ diffuse reflectance infrared Fourier transform spectroscopy unveil that the superior CO selectivity is attributed to the lower energy of *CO desorption than that of hydrogenation to *HCO. This meticulous design sheds light on the modification of perovskite-based multifunctional materials and enlightens conscious optimization of semiconductor-based heterostructures with desirable charge transfer for catalysis and optoelectronic applications.

Farrerol suppresses osteoclast differentiation and postmenopausal osteoporosis by inhibiting the nuclear factor kappa B signaling pathway.

Excessive bone resorption caused by upregulated osteoclast activity is a key factor in osteoporosis pathogenesis. Farrerol is a typical natural flavanone and exhibits various pharmacological actions. However, the role and mechanism of action of farrerol in osteoclast differentiation regulation remain unclear. This study aimed to evaluate the effects and mechanism of farrerol on the inhibition of osteoclastogenesis. Tartrate-resistant acid phosphatase staining, F-actin staining, and the pit formation assay were performed to examine the differentiation and functions of osteoclasts in vitro. The expression of proteins associated with the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways was analyzed by western blotting. Dual X-ray absorptiometry, microcomputed tomography, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of farrerol in vivo bone loss prevention. The effects of farrerol on osteoblastic bone formation were assessed using alkaline phosphatase, alizarin red S staining, and calcein-alizarin red S double labeling. Farrerol inhibited osteoclastogenesis and bone resorption in osteoclasts by suppressing nuclear factor kappa B signaling rather than mitogen-activated protein kinase signaling in vitro. Farrerol protected mice against ovariectomy-induced bone loss by inhibiting osteoclast-mediated bone resorption, instead of promoting osteoblast-mediated bone formation in vivo. The findings of the current study revealed that farrerol is a potential therapeutic agent for osteoporosis.

Capsule Shedding and Membrane Binding Enhanced Photodynamic Killing of Gram-Negative Bacteria by a Unimolecular Conjugated Polyelectrolyte.

The development of new antimicrobial agents to treat infections caused by Gram-negative bacteria is of paramount importance due to increased antibiotic resistance worldwide. Herein, we show that a water-soluble porphyrin-cored hyperbranched conjugated polyelectrolyte (PorHP) exhibits high photodynamic bactericidal activity against the Gram-negative bacteria tested, including a multidrug-resistant (MDR) pathogen, while demonstrating low cytotoxicity toward mammalian cells. Comprehensive analyses reveal that the antimicrobial activity of PorHP proceeds via a multimodal mechanism by effective bacterial capsule shedding, strong bacterial outer membrane binding, and singlet oxygen generation. Through this multimodal antimicrobial mechanism, PorHP displays significant performance for Gram-negative bacteria with >99.9% photodynamic killing efficacy. Overall, PorHP shows great potential as an antimicrobial agent in fighting the growing threat of Gram-negative bacteria.

Enhanced Aquathermolysis of Water-Heavy Oil-Ethanol Catalyzed by B@Zn(II)L at Low Temperature.

In order to study the synergistic effects of exogenous catalysts and in situ minerals in the reservoir during heavy oil aquathermolysis, in this paper, a series of simple supported transition metal complexes were prepared using sodium citrate, chloride salts and bentonite, and their catalytic viscosity reduction performances for heavy oil were investigated. Bentonite complex catalyst marked as B@Zn(II)L appears to be the most effective complex. B@Zn(II)L was characterized by scanning electron microscopy (SEM), Fourier-Transform Infrared (FTIR) spectroscopy, thermo-gravimetric analysis (TGA) and N2 adsorption-desorption isotherms. Under optimized conditions, the viscosity of the heavy oil was decreased by 88.3%. The reaction temperature was reduced by about 70 °C compared with the traditional reaction. The results of the group composition analysis and the elemental content of the heavy oil indicate that the resin and asphaltene content decreases, and the saturated and aromatic HC content increases. The results of TGA and DSC of the heavy oil show that the macromolecular substances in the heavy oil were cracked into small molecules with low boiling points by the reaction. GC-MS examination of water-soluble polar compounds post-reaction indicates that B@Zn(II)L can diminish the quantity of polar substances in heavy oil and lower the aromatic nature of these compounds. Thiophene and quinoline were utilized as model compounds to investigate the reaction mechanism. GC-MS analysis revealed that C-C, C-N and C-S bonds were cleaved during the reaction, leading to a decrease in the viscosity of heavy oil.

Exosomes derived from bone marrow mesenchymal stem cells pretreated with decellularized extracellular matrix enhance the alleviation of osteoarthritis through miR-3473b/phosphatase and tensin homolog axis.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative articular disease for which there is no effective treatment. Progress has been made in mesenchymal stem cell (MSC)-based therapy in OA, and the efficacy has been demonstrated to be a result of paracrine exosomes from MSCs. Decellularized extracellular matrix (dECM) provides an optimum microenvironment for the expansion of MSCs. In the present study, we aimed to investigate whether exosomes isolated from bone marrow mesenchymal stem cells (BMSCs) with dECM pretreatment (dECM-BMSC-Exos) enhance the amelioration of OA. METHODS: Exosomes from BMSCs with or without dECM pretreatment were isolated. We measured and compared the effect of the BMSC-Exo and dECM-BMSC-Exo on interleukin (IL)-1ß-induced chondrocytes by analyzing proliferation, anabolism and catabolism, migration and apoptosis in vitro. The in vivo experiment was performed by articular injection of exosomes into DMM mice, followed by histological evaluation of cartilage. MicroRNA sequencing of exosomes was performed on BMSC-Exo and dECM-BMSC-Exo to investigate the underlying mechanism. The function of miR-3473b was validated by rescue studies in vitro and in vivo using antagomir-3473b. RESULTS: IL-1ß-treated chondrocytes treated with dECM-BMSC-Exos showed enhanced proliferation, anabolism, migration and anti-apoptosis properties compared to BMSC-Exos. DMM mice injected with dECM-BMSC-Exo showed better cartilage regeneration than those injected with BMSC-Exo. Interestingly, miR-3473b was significantly elevated in dECM-BMSC-Exos and was found to mediate the protective effect in chondrocytes by targeting phosphatase and tensin homolog (PTEN), which activated the PTEN/AKT signaling pathway. CONCLUSIONS: dECM-BMSC-Exo can enhance the alleviation of osteoarthritis via promoting migration, improving anabolism and inhibiting apoptosis of chondrocytes by upregulating miR-3473b, which targets PTEN.

Oil-Soluble Exogenous Catalysts and Reservoir Minerals Synergistically Catalyze the Aquathermolysis of Heavy Oil.

Oil is the "blood" and economic lifeblood of modern industry, but traditional light crude oil has been over-consumed, and it has been difficult to meet human demand for energy, so the exploitation of heavy oil is particularly important. In this paper, an oil-soluble catalyst was synthesized to catalyze the pyrolysis reaction of heavy oil in collaboration with reservoir minerals, so as to achieve efficient viscosity reduction of heavy oil and reduce production costs. The experimental results showed that Zn(II)O + K had the best synergistic viscosity reduction effect after the aquathermolysis of No. 1 oil sample under the reaction conditions of 180 °C, 4 h, 30% of water, and 0.2% of catalyst, respectively, and the viscosity reduction rate was 61.74%. Under the catalysis of the isopropanol system, the viscosity reduction rate was increased to 91.22%. A series of characterizations such as freezing point, thermogravimetric analysis, DSC analysis, component analysis, gas chromatography, wax crystal morphology analysis, and GC-MS analysis of aqueous organic matter were carried out on heavy oil after reaction by different reaction systems, and it could be verified that the viscosity of heavy oil was reduced. Finally, through the study of the reaction mechanism of the model compound, combined with the aqueous phase analysis, it can be clearly found that the depolymerization between macromolecules, the breaking of heteroatom chains, hydrogenation, ring opening, and other effects mainly occur during the reaction, thereby weakening the van der Waals force and hydrogen bond of the recombinant interval, inhibiting the formation of grid structure in heavy oil and effectively reducing the viscosity of heavy oil.

Encapsulation of Dual-Passivated Perovskite Quantum Dots for Bio-Imaging.

Due to their marvelous electrical and optical properties, perovskite nanocrystals have reached remarkable landmarks in solar cells, light-emitting diodes, and photodetectors. However, the intrinsic instability of ionic perovskites, which would undergo an undesirable phase transition and decompose rapidly in ambient humidity, limits their long-term practical deployment. To address this challenge, halogenated trimethoxysilane as the passivation additive is chosen, which utilizes simultaneous halide and silica passivation to enhance the stability of perovskite nanoparticles via a dual-passivation mechanism. The processable nanoparticles show high photoluminescence quantum yield, tunable fluorescence wavelength, and excellent resistance against air and water, highlighting great potential as green to deep-red bio-labels after further phospholipid encapsulation. This work demonstrates that the dual-passivation mechanism could be used to maintain the long-term stability of ionic crystals, which sheds light on the opportunity of halide perovskite nanoparticles for usage in a humid environment.

Iron overload-induced ferroptosis of osteoblasts inhibits osteogenesis and promotes osteoporosis: An in vitro and in vivo study.

Growing evidence indicates that iron overload is an independent risk factor for osteoporosis. However, the mechanisms are not fully understood. The purpose of our study was to determine whether iron overload could lead to ferroptosis in osteoblasts and to explore whether ferroptosis of osteoblasts is involved in iron overload-induced osteoporosis in vitro and in vivo. Ferric ammonium citrate was used to mimic iron overload conditions, while deferoxamine and ferrostatin-1 were used to inhibit ferroptosis of MC3T3-E1 cells in vitro. The ferroptosis, osteogenic differentiation and mineralization of MC3T3-E1 cells were assessed in vitro. A mouse iron overload model was established using iron dextran. Immunohistochemical analysis was performed to determine ferroptosis of osteoblasts in vivo. Enzyme-linked immunosorbent assays and calcein-alizarin red S labelling were used to assess new bone formation. Dual x-ray absorptiometry, micro-computed tomography and histopathological analysis were conducted to evaluate osteoporosis. The results showed that iron overload reduced cell viability, superoxide dismutase and glutathione levels, increased reactive oxygen species generation, lipid peroxidation, malondialdehyde levels and ferroptosis-related protein expression, and induced ultrastructural changes in mitochondria. Iron overload could also inhibit osteogenic differentiation and mineralization in vitro. Inhibiting ferroptosis reversed the changes described above. Iron overload inhibited osteogenesis, promoted the ferroptosis of osteoblasts and induced osteoporosis in vivo, which could also be improved by deferoxamine and ferrostatin-1. These results demonstrate that ferroptosis of osteoblasts plays a crucial role in iron overload-induced osteoporosis. Maintaining iron homeostasis and targeting ferroptosis of osteoblasts might be potential measures of treating or preventing iron overload-induced osteoporosis.

Development and validation of a prediction model for glucocorticoid-associated osteonecrosis of the femoral head by targeted sequencing.

OBJECTIVE: To develop and validate a prediction model based on targeted sequencing for glucocorticoid (GC)-associated osteonecrosis of the femoral head (GA-ONFH) in GC-treated adults. METHODS: This two-centre retrospective study was conducted between July 2015 and April 2019 at Zhongshan Hospital (training set) and the Sixth People's Hospital (test set) in Shanghai, China. All patients had a history of GC therapy, with a dose exceeding 2000 mg equivalent prednisone within 6 weeks. Patients were divided into two groups according to whether they were diagnosed with GA-ONFH within 2 years after GC initiation. Blood or saliva samples were collected for targeted sequencing of 358 single nucleotide polymorphisms and genetic risk score (GRS) calculating for developing GA-ONFH prediction model. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate and validate the model. RESULTS: . The training set comprised 117 patients, while the test set comprised 30 patients for external validation. Logistic regression analysis showed that GRS was significantly associated with GA-ONFH (OR 1.87, 95% CI: 1.48, 2.37). The ROC and DCA curves showed that the multivariate model considering GRS, age at GC initial, sex and underlying diseases had a discrimination with area under the ROC curve (AUC) of 0.98 (95% CI: 0.96, 1.00). This model was further externally validated using the test set with an AUC of 0.91 (95% CI: 0.81, 1.00). CONCLUSION: Our prediction model comprising GRS, age, sex and underlying diseases yields valid predictions of GA-ONFH incidence. It may facilitate effective screening and prevention strategies of GA-ONFH.

Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

Engineering Living Mitochondria with AIE Photosensitizer for Synergistic Cancer Cell Ablation.

Photodynamic therapy (PDT) has been increasingly studied in cancer treatment, and several factors have been identified to limit the PDT therapeutic efficiency. Taking Bcl-2 protein as an example, its overexpressing in cancer cells could strengthen the antioxidant and antiapoptotic capability of the cells, making PDT less effective in cancer cell treatment. To address this issue, we developed an engineered living system by integrating an aggregation-induced emission photosensitizer (AIE PS) with bioactive mitochondria (Mito-AIEgen-lipid) for enhanced PDT. The AIE PS engineered mitochondria could not only change the energetic metabolism of cancer cells from aerobic glycolysis to normal oxide phosphorylation for cancer cell growth inhibition but also activate the apoptotic pathway and reduce the expression of antiapoptotic protein Bcl-2. This specific organelle-based living system holds great promise to enhance the therapeutic efficiency of PDT by integrating the advantages of synthetic organic small molecules with biological components.

Cancer-Cell-Activated in situ Synthesis of Mitochondria-Targeting AIE Photosensitizer for Precise Photodynamic Therapy.

Maximization of phototoxic damage on tumor with minimized side effect on normal tissue is essential for effective anticancer photodynamic therapy (PDT). This requires highly cancer-cell-specific or even cancer-cell-organelle-specific synthesis or delivery of efficient photosensitizers (PSs) in vitro and in vivo, which is difficult to achieve. Herein, we report a strategy of cancer-cell-activated PS synthesis, by which an efficient mitochondria-targeting photosensitizer with aggregation-induced-emission (AIE) feature can be selectively synthesized as an efficient image-guided PDT agent inside cancer cells. MOF-199, a CuII -based metal-organic framework, was selected as an inert carrier to load the PS precursors for efficient delivery and served as a CuI catalyst source for in situ click reaction to form PSs exclusively in cancer cells. The in situ synthesized PS showed mitochondria-targeting capability, allowing potent cancer-cell-specific ablation under light irradiation. The high specificity of PSs produced in cancer cells also makes it safer post-treatment.

Fast and High-Throughput Evaluation of Photodynamic Effect by Monitoring Specific Protein Oxidation with MALDI-TOF Mass Spectrometry.

In antibacterial practices by photodynamic treatment, bacteria are incubated with photosensitizers and then oxidized to death by generating reactive oxygen species (ROS) under light irradiation. Generally, Luria-Bertani (LB) agar colony is a conventional method to evaluate the photodynamic effect. However, this method is time consuming, easily disturbed by pollutants, and limited to the analysis of a pure bacteria sample. Herein, we introduce a novel method of photodynamic effect evaluation through in situ detection of specific protein oxidation by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) with only 1 µL of sample in a fast (less than 1 min per sample) and high-throughput (up to 384 samples per run) way. The oxidation rates of specific proteins stayed highly consistent with bactericidal rates and thus MALDI-TOF MS might be able to replace the LB agar colony to evaluate the photodynamic effect. With the present method, several experimental conditions including different photosensitizer types, dosage controls, and different illumination times were easily screened to optimize photodynamic effect. Photodynamic effects of various bacteria species, cancer cells, and even mixture samples were also evaluated. The results demonstrate the promising application of MALDI-TOF MS in evaluating the photodynamic effect of each component in a mixture sample without any separation or purification, which could not be achieved by the traditional LB agar colony method.

Visualization and In†Situ Ablation of Intracellular Bacterial Pathogens through Metabolic Labeling.

Protected by the host cells, the hidden intracellular bacteria are typically difficult to kill by common antibiotics and cannot be visualized without complex cellular pretreatments. Herein, we successfully developed a bacteria-metabolizable dual-functional probe TPEPy-d-Ala, which is based on d-alanine and a photosensitizer with aggregation-induced emission for fluorescence turn-on imaging of intracellular bacteria in living host cells and photodynamic ablation in situ. Once metabolically incorporated into bacterial peptidoglycan, the intramolecular motions of TPEPy-d-Ala are inhibited, leading to an enhanced fluorescent signal, which allows the clear visualization of the intracellular bacteria. Moreover, TPEPy-d-Ala can effectively ablate the labeled intracellular bacteria in situ owing to covalent ligation to peptidoglycan, yielding a low intracellular minimum inhibitory concentration (MIC) of 20±0.5 µg mL-1 , much more efficient than that of a commonly used antibiotic, vancomycin.

Near-Infrared Laser-Driven in Situ Self-Assembly as a General Strategy for Deep Tumor Therapy.

Nanotherapeutics have encountered some bottleneck problems in cancer therapy, such as poor penetration and inefficient accumulation in tumor site. We herein developed a novel strategy for deep tissue penetration in molecular level and near-infrared (NIR) laser guided in situ self-assembly to solve these challenges. For the proof-of-concept study, we synthesized the polymer-peptide conjugates (PPCs) composed of (i) poly(ß-thioester) as thermoresponsive backbone, (ii) functional peptides (cytotoxic peptide and cell-penetrating peptide), and (iii) the NIR molecule with photothermal property. The PPCs in the molecular level with small size (<10 nm) can penetrate deeply into the interior of the tumor at body temperature. Under the irradiation of NIR laser, the temperature rise induced by photothermal molecules led to the intratumoral self-assembly of thermoresponsive PPCs. The resultant spherical nanoparticles can accumulate in tumor and enter cells effectively, inducing cell apoptosis by destroying mitochondria membrane. Through the site-specific size control, a variety of merits of PPCs are realized including deep tumor penetration, enhanced accumulation, and cellular internalization in vivo. Taking advantage of the NIR guided in situ assembly strategy, numerous polymeric or nanoscaled therapeutics with high anticancer activity can be exploited.

An AIEgen-Peptide Conjugate as a Phototheranostic Agent for Phagosome-Entrapped Bacteria.

The detection and elimination of intracellular bacteria remain a major challenge. In this work, we report an aggregation-induced emission (AIE) bioprobe that can detect bacterial infection and kill bacteria surviving inside macrophages through a dynamic process, notably specific molecular tailoring of the probe by caspase-1 activation in infected macrophages and accumulation of the residue on phagosomes containing bacteria, leading to light-up fluorescent signals. Moreover, the AIEgen can serve as a photosensitizer for generation of reactive oxygen species (ROS); and the average ROS indicator fluorescent signal intensity per unit area in the bacterial phagosomes is approximately 2.7-fold higher than that in the cytoplasm. This, in turn, induces bacteria killing with high efficiency and minimal cytotoxicity towards macrophages. We envision that this specific light-up bioprobe may provide a new approach for selective and sensitive detection and eradication of intracellular bacterial infections.

A Cross-linked Conjugated Polymer Photosensitizer Enables Efficient Sunlight-Induced Photooxidation.

Photooxidation under sunlight has potential in organic synthesis, bacterial killing, and organic waste treatment. Photosensitizers (PSs) can play an important role in this process. High 1 O2 generation efficiency and excellent photostability under sunlight, as well as easy recyclability are ideal properties for PSs, but are not easy to achieve simultaneously. Herein, a pure organic porous conjugated polymer PS, CPTF, shows great photostability, large specific surface area, and high 1 O2 generation efficiency under sunlight for photooxidation. For the oxidation of aromatic aldehyde to aromatic acid, the PS catalyst shows excellent recyclability, and enables solvent-free reactions in high yields both under direct sunlight and simulated AM 1.5G irradiation. In addition, the successful application of CPTF as an antibacterial agent and organic waste decomposition under simulated AM 1.5G irradiation indicates the potential of CPTF in sunlight-induced waste water treatment.

In Situ Monitoring Intracellular Structural Change of Nanovehicles through Photoacoustic Signals Based on Phenylboronate-Linked RGD-Dextran/Purpurin 18 Conjugates.

The stimuli-responsive polymeric nanocarriers have been studied extensively, and their structural changes in cells are important for the controlled intracellular drug release. The present work reported RGD-dextran/purpurin 18 conjugates with pH-responsive phenylboronate as spacer for monitoring the structural change of nanovehicles through ratiometric photoacoustic (PA) signal. Phenylboronic acid modified purpurin 18 (NPBA-P18) could attach onto the RGD-decorated dextran (RGD-Dex), and the resulting RGD-Dex/NPBA-P18 (RDNP) conjugates with different molar ratios of RGD-Dex and NPBA-P18 were prepared. When the moles of NPBA-P18 were equivalent to more than triple of RGD-Dex, the single-stranded RDNP conjugates could self-assemble into nanoparticles in aqueous solution due to the fairly strong hydrophobicity of NPBA-P18. The pH-responsive aggregations of NPBA-P18 were investigated by UV-vis, fluorescence, and circular dichroism spectra, as well as transmission electron microscope. Based on distinct PA signals between monomeric and aggregated state, ratiometric PA signal of I750/I710 could be presented to trace the structural change progress. Compared with RDNP single chains, the nanoparticles exhibited effective cellular internalization through endocytosis pathway. Furthermore, the nanoparticles could form well-ordered aggregates responding to intracellular acidic environment, and the resulting structural change was also monitored by ratiometric PA signal. Therefore, the noninvasive PA approach could provide a deep insight into monitoring the intracellular structural change process of stimuli-responsive nanocarriers.

NIR Light Propulsive Janus-like Nanohybrids for Enhanced Photothermal Tumor Therapy.

Au-BP7@SP nanohybrids with active motion under NIR laser irradiation can effectively enhance the temperature of tumor potentially by converting the kinetic energy to thermal energy, enhancing the killing efficiency of the tumor cells compared with Au@SP. The study provides an insight of nanohybrids' effect on photothermal treatment and opens a new avenue to cancer treatment by using self-propulsion Janus nanohybrids.