Ultrasound-Chargeable Persistent Luminescence Nanoparticles to Generate Self-Propelled Motion and Photothermal/NO Therapy for Synergistic Tumor Treatment.

Cancer phototherapy indicates advantages in ease of manipulation, negligible drug resistance, and spatiotemporal control but is confronted with challenges in tumor cell accessibility and intermittent light excitation. Herein, we propose a strategy with persistent luminescence (PL)-excited photothermal therapy (PTT), concurrent thermophoresis-propelled motion, and PL-triggered NO release, where PL emission is chargeable by ultrasonication for readily applicable to deep tumors. Mechanoluminescent (ML) nanodots of SrAl2O4:Eu2+ (SAOE) and PL nanodots of ZnGa2O4:Cr3+ (ZGC) were deposited on mesoporous silicates to obtain mSZ nanoparticles (NPs), followed by partially coating with polydopamine (PDA) caps and loading NO donors to prepare Janus mSZ@PDA-NO NPs. The ML emission bands of SAOE nanodots overlap with the excitation band of ZGC, and the persistent near-infrared (NIR) emission could be repeatedly activated by ultrasonication. The PL emission acts as an internal NIR source to produce a thermophoretic force and NO gas propellers to drive the motion of Janus NPs. Compared with the commonly used intermittent NIR illumination at both 660 and 808 nm, the persistent motion of ultrasound-activated NPs enhances cellular uptake and long-lasting PTT and intracellular NO levels to combat tumor cells without the use of any chemotherapeutic drugs. The ultrasound-activated persistent motion promotes intratumoral accumulation and tumor distribution of PTT/NO therapeutics and exhibits significantly higher tumor growth inhibition, longer animal survival, and larger intratumoral NO levels than those who experience external NIR illumination. Thus, this study demonstrates a strategy to activate PL emissions and construct PL-excited nanomotors for phototherapy in deep tissues.

Pyroelectric Janus nanomotors to promote cell internalization and synergistic tumor therapy.

The tumor diffusion and cell internalization are the major obstacles to improving delivery efficacy of therapeutic agents. External electric fields have shown strong effect on the cell membrane polarization and fluidity, but usually need complicated power management circuits. Herein, in situ generation of microelectric field on nanoparticles (NPs) is proposed to overcome these delivery barriers. Janus tBT@PDA-CPT NPs were developed through partially coating of polydopamine (PDA) caps on pyroelectric tetragonal BaTiO3 (tBT) NPs and then camptothecin (CPT) conjugation via disulfide linkages. For comparison, cBT@PDA-CPT NPs were prepared from non-pyroelectric cubic BaTiO3 (cBT) as control. Near-infrared (NIR) illumination on PDA caps of the Janus NPs produces asymmetric thermophoretic force to drive NP motion for tumor accumulation, deep tissue penetration and effective cell interaction. Photothermally created temperature variations on tBT NPs build pyroelectric potentials to selectively change the membrane potential of tumor cells other than normal cells and exhibit a dominated role in enhancing tumor cell internalization and cytotoxicity. The combination index analysis confirms the synergistic effect of pyroelectric dynamic therapy (PEDT), chemotherapy and photothermal therapy (PTT), leading to full inhibition of tumor growth and noticeable extension of animal survival at significant lower CPT doses. The mild PTT/PEDT, the reduced CPT dose and the selective toxicity to tumor cells have achieved favorable treatment safety after tBT@PDA-CPT/NIR treatment. Therefore, in response to the differences in membrane potentials and glutathione levels between tumor and normal cells, we have demonstrated a concise design to achieve thermophoresis-driven motion, pyroelectric potential-enhanced cell internalization and PTT/PEDT/chemotherapy-synergized antitumor treatment.

Pyroelectric Janus nanomotors for synergistic electrodynamic-photothermal-antibiotic therapies of bacterial infections.

Antibacterial electrotherapy is currently activated by external electric field or self-powered generators, but usually needs complicated power management circuits. Herein, near-infrared illumination (NIR) of pyroelectric nanoparticles (NPs) produces a built-in electric field to address the effectiveness and safety concerns in the antibacterial treatment. Janus tBT@PDA NPs were obtained by capping polydopamine (PDA) on tetragonal BaTiO3 (tBT) NPs through defining the polymerization time, followed by ciprofloxacin (CIP) loading on the PDA caps to fabricate Janus tBT@PDA-Cip NPs. NIR illumination of PDA caps creates temperature variations on tBT NPs to generate photothermal and pyroelectric effects. Finite element simulation reveals a pyroelectric potential of over 1 V and sufficient reactive oxygen species (ROS) are produced to exhibit pyroelectric dynamic therapy (PEDT). The elevated temperature on one side of the Janus NPs produces thermophoretic force to drive NP motion, which enhances interactions with bacteria and overcomes limitations in the short action distance and lifespan of ROS. The pyroelectric field accelerates CIP release through weakening the π-π stacking and electrostatic interaction with PDA and also interrupts membrane potentials of bacteria to enhance CIP invasion into bacteria. The synergistic antibacterial effect of pyroelectric tBT@PDA-Cip NPs causes the fully recovery of S. aureus-infected skin wounds and regeneration of intact epidermis, blood vessels and hair follicles, while no obvious pathological change or inflammatory lesion is detected in the major organs. Thus, the pyroelectric Janus nanomotors demonstrate synergistic PEDT/photothermal/antibiotic effects to enhance antibacterial efficacy while avoiding the necessity of excessive heat, ROS and antibiotic doses. STATEMENT OF SIGNIFICANCE: Antibacterial treatment is challenged by antibiotics-derived side effects and the evolution of resistant strains. Phototherapy is commonly associated with excessive heat and oxidative stress, and their combinations with other agents are especially encouraged to strengthen antibacterial efficacy while alleviating the associated side effects. Electric field is another activator to generate antibacterial abilities, but usually requires complicated power management and bulk electrodes, making it inconvenient in a biological setup. To address these challenges, we propose a strategy to generate microelectric field on nanoparticles themselves and achieve synergistic electrodynamic-photothermal-antibiotic therapies. The pyroelectric effect weakens interactions between nanoparticles and antibiotics to accelerate drug release, and the built-in pyroelectric field increases membrane fluidity to enhance bacterial uptake of antibiotics.

Surface decoration of black phosphorus nanosheets to generate oxygen and release 1O2 for photodynamic killing of bacteria.

Photodynamic therapy (PDT) has evolved as an essential method for infection control, but is confronted with challenges in terms of low oxygen supply, possible toxicity during light irradiation, and nonpersistent action. Herein, to address these limitations, black phosphorus (BP) is used as a photosensitizer and decorated with Pt nanoparticles and aminobenzyl-2-pyridone (APy) moieties to obtain BP@APy-Pt. The stability of BP is improved through the capture and occupation of lone-pair electrons after reductive deposition of Pt nanoparticles and covalent conjugation of APy. Pt nanoparticles on BP@APy-Pt catalyze the decomposition of endogenous H2O2 to produce oxygen for consecutive cycles with a stable production capacity. The light exposure to BP@APy-Pt generates significantly higher 1O2 levels than those of BP/light, and the generated 1O2 is partially captured by APy moieties. The captured 1O2 during 20 min of illumination shows a constant release for 24 h in the dark. The cycled storage and release feature eliminates the toxicity of 1O2 at high levels during illumination and leads to efficient destruction of S. aureus and P. aeruginosa. Compared to the healing rates after treatment with BP/light (57.6%), BP@Pt/light (64.8%), BP@APy/light (77.8%), and BP@APy-Pt (48.5%), the skin wounds with infected S. aureus are fully healed after BP@APy-Pt/light treatment. Blood vessels and hair follicles are regenerated to resemble those of normal skin. Thus, this study expands the PDT strategy through integration with oxygen generation, 1O2 storage, and persistent release to promote bactericidal efficacy and eliminate side effects.

Metabolite Profiling and Transcriptome Analyses Provide Insights into the Flavonoid Biosynthesis in the Developing Seed of Tartary Buckwheat (Fagopyrum tataricum).

Tartary buckwheat (Fagopyrum tataricum) seeds are rich in flavonoids. However, the detailed flavonoid compositions and the molecular basis of flavonoid biosynthesis in tartary buckwheat seeds remain largely unclear. Here, we performed a combined metabolite profiling and transcriptome analysis to identify flavonoid compositions and characterize genes involved in flavonoid biosynthesis in the developing tartary buckwheat seeds. In total, 234 flavonoids, including 10 isoflavones, were identified. Of these, 80 flavonoids were significantly differential accumulation during seed development. Transcriptome analysis indicated that most structural genes and some potential regulatory genes of flavonoid biosynthesis were significantly differentially expressed in the course of seed development. Correlation analysis between transcriptome and metabolite profiling shown that the expression patterns of some differentially expressed structural genes and regulatory genes were more consistent with the changes in flavonoids profiles during seed development and promoted one SG7 subgroup R2R3-MYB transcription factors (FtPinG0009153900.01) was identified as the key regulatory gene of flavonoid biosynthesis. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in tartary buckwheat seeds and the further development of tartary buckwheat health products.

Traditional Chinese medicine health management guidance to the community of puerperal women’s breast-feeding / 国际中医中药杂志

Objective By combining the traditional Chinese medicine(TCM) health care service and the current community puerperal women's health management, to explore the feasibility of TCM health management in the grass-roots community on puerperal women’s breast-feeding. Methods 440 patients meeting the inclusion criteria of puerperal women according to the neighborhood of residence were recruited into a non TCM intervention group of 225 people, and a TCM intervention group of 215 people. The non TCM intervention group was given health guidance on puerperal women. On such basis, the TCM intervention group was further cooperated with appropriate technical guidance of TCM. Puerperal women breastfeeding before and after the intervention was studied. Results After the intervention, the milk shortage of puerperal women breastfeeding rate of TCM intervention group was higher than the non TCM intervention group, 76.9% (60/78) vs. 56.9% (41/72), and mixed feeding rate was lower 21.8% (17/78) vs. 40.3%(29/72), the difference was statistically significant (χ2=5.916, 5.178; P < 0.05). The rate of breast feeding and mixed feeding rate were also statistically different between the TCM intervention group and the non TCM intervention group 78.1%(168/215) and 17.2% (37/215) vs. 62.7% (141/225) and 33.3% (75/225), (χ2=11.860, 14.226; P<0.01). Conclusion TCM health management guidance on puerperal women in the community can effectively improve the hypogalactia puerperal women's breastfeeding rate.