Microwave photonic sideband selector based on thin-film lithium niobate platform

We propose and demonstrate an integrated microwave photonic sideband selector based on the thin-film lithium niobate(TFLN)platform by integrating an electro-optic Mach-Zehnder modulator(MZM)and a thermo-optic tunable flat-top microring filter.The sideband selector has two functions:electro-optic modulation of wideband RF signal and sideband selection.The microwave photonic sideband selector supports processing RF signals up to 40 GHz,with undesired sidebands effectively suppressed by more than 25 d B.The demonstrated device shows great potential for TFLN integrated technology in microwave photonic applications,such as mixing and frequency measurement.

Advances in aggregatable nanoparticles for tumor-targeted drug delivery

Recent days,aggregatable nanoparticles,which can specifically respond to certain stimulus,have shown great potential in tumor-targeted drug delivery with prolonged retention and deeper penetration.In this review,we summarize recent advances in design of aggregatable nanoparticles by different stimuli.Internal(pH and enzyme)and external(light,temperature and ROS)stimuli are introduced for a comprehensive description.Moreover,the aggregated nanoparticles usually exhibit photothermal,photoacoustic,PET and enhanced MRI contrast,which is also described.In the end,we discuss about the potential applications and challenges for the future clinical translation.

Intelligent lesion blood–brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection

The treatment of Alzheimer's disease(AD)is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier(BBB)permeability and unsatisfactory intra-brain distribution of drugs.Therefore,we established an ibuprofen and FK506 encapsulated drug co-delivery system(Ibu&FK@RNPs),which can target the receptor of advanced glycation endproducts(RAGE)and response to the high level of reactive oxygen species(ROS)in AD.RAGE is highly and specifically expressed on the lesion neurovascular unit of AD,this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain.Meanwhile,these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS.As a result,the cognition of AD mice was significantly improved and the quantity of Aβplaques was decreased.Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons.Besides,the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1βin the brain.Overall,Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion.Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.

Dual-responsive nanoparticles with transformable shape and reversible charge for amplified chemo-photodynamic therapy of breast cancer

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention,which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6(Ce6), hydrophilic chemotherapeutic drug berberrubine(BBR) and matrix metalloproteinase-2(MMP-2) response peptide(PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6(BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine(PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively,we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis

Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.

Glymphatic System and Subsidiary Pathways Drive Nanoparticles Away from the Brain

Although drug delivery systems(DDS)are efficient in brain delivery,they face failure in clinical settings due to their potential toxicity to the central nervous system.Little is known about where the DDS will go after brain delivery,and no specific elimination route that shares a passage with DDS has been verified.Hence,identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical translation.In this study,we investigated nonreactive gold nanoclusters,which can deliver into the brain,to determine the elimination route of DDS.Subsequently,nanoclusters in the brain were systemically tracked and were found to be critically drained by the glymphatic system from the blood vessel basement membrane to periphery circulations(77.8±23.2%and 43.7±23.4%contribution).Furthermore,the nanoclusters could be actively transported across the blood-brain barrier(BBB)by exosomes(30.5±27.3%and 29.2±7.1%contribution).In addition,microglia promoted glymphatic drainage and passage across the BBB.The simultaneous work of the glymphatic system,BBB,and microglia revealed the fate of gold nanoclusters for brain delivery and provided a basis for further braindelivery DDS.