Fluorescence-enhanced covalent organic framework nanosystem for tumor imaging and photothermal therapy.

Fluorescent dyes, as a key factor in fluorescence imaging, usually exhibit a low signal-to-noise ratio (SNR) due to the limited loading capacities of delivery systems (usually less than 10.0 wt%) and their uncontrolled release. Herein, we developed a type of pH-responsive nanoplatform (MnO2/ZnCOF@Au&BSA) based on a zinc porphyrin covalent organic framework (COF), in which the zinc porphyrin (ZnPor) loading rate is 22.5 wt%. At pH = 7.4, the interlinked ZnPor in the assembly state did not show a fluorescence signal ("off" state). Together with the pH-triggered disintegration of ZnCOF in tumor cells (pH = 5.5), the scattered ZnPor displayed an obvious fluorescence signal recovery ("on" state). Simultaneously, the shed BSA-coated gold nanoparticles ingeniously caused the fluorescence signal to be further amplified through the metal-enhanced fluorescence effect, which was about 3.0-fold higher in vivo than in the free ZnPor group. Combined with the excellent photothermal therapy effect by the nanoplatform itself with the tumor inhibition rate of 79.5%, this nanosystem effectively solves the problem of low loading capacities and imaging SNR by traditional delivery systems, and successfully develops the potential of COFs for fluorescence imaging, achieving the purpose of integration of diagnosis and treatment.

Near-infrared-light induced nanoparticles with enhanced tumor tissue penetration and intelligent drug release.

Tumor tissue presents much denser and stiffer extracellular matrix (ECM), which can hinder the penetration of most nanoparticles (NPs) and contribute to the tumor cell proliferation. Here, NIR-activated losartan was encapsulated in hollow mesoporous prussian blue nanoparticles (HMPBs) to degrade ECM. The results showed that losartan enhanced the penetration of DOX, 1.47% of the injected dose (ID) of DOX reached the tumor tissues, which was 3.00-fold higher than the control group (0.49%). In addition, as the existence of thermo-sensitive lauric acid, (Losartan + DOX)@HMPBs could achieve near "zero drug leakage" during blood circulation, so as to reduce the damage of DOX to normal tissues. Furthermore, the animal experiments proved tumor inhibition ability of (Losartan + DOX)@HMPBs in synergistic of photothermal/chemotherapy, with the tumor growth inhibition rate of 81.3%. Taken together, these findings can be a candidate for developing vectors with enhanced tumor penetration and therapeutic effect in future clinical application. STATEMENT OF SIGNIFICANCE: Due to the existence of denser extracellular matrices (ECM), only 0.7% of the administered nanoparticles dose is delivered to tumor, which will limit the tumors' therapeutic effect. Degradation of ECM can improve the penetration of nanoparticles in tumors. However, no researchers has encapsulated losartan in nanoparticles to degrade ECM. Herein, we developed a NIR induced losartan and DOX co-delivery system based on hollow mesoporous prussian blue nanoparticles (HMPBs) to degrade ECM and improve the penetration of nanoparticles in tumors. The prepared nanoparticles can also acheive near "zero drug leakage" during blood circulation and "fixed-point drug release" in tumor, so as to reduce the damage of DOX to normal tissues. We believe the prepared nanoparticles provide a new platform for cancer treatment.

Valproic acid attenuates inflammation of optic nerve and apoptosis of retinal ganglion cells in a rat model of optic neuritis.

AIMS: Optic neuritis (ON) is an inflammatory disease of the optic nerve, which often occurs in patients with multiple sclerosis (MS) and leads to retinal ganglion cell (RGC) death and even severe visual loss. Valproic acid (VPA) is a short-chain branched fatty acid with anti-epileptic, neuro-protective and anti-inflammatory effects. Here, we examined the effects of VPA in experimental autoimmune encephalomyelitis (EAE) rats and explored the underlying mechanisms. MAIN METHODS: EAE was induced by subcutaneous injection with myelin basic protein, emulsified with complete Freund's adjuvant and Mycobacterium tuberculosis H37Ra into the Lewis rats. Subsequently, animals in the VPA groups were treated orally with VPA (250 or 500 mg/kg) once a day for 13 days. KEY FINDINGS: VPA treatment significantly attenuated inflammation and microgliosis in optic nerve in EAE-ON rats, as evidenced by the decrease in the mRNA levels of interferon (INF)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-17, and inducible nitric oxide synthase (iNOS), the suppression in nuclear factor (NF)-κB signal pathway as well as the down-regulation of CD11b expression in optic nerve. Additionally, the apoptotic RGCs were remarkably increased in the EAE retina, which was inhibited by VPA treatment. Consistent with the TUNEL staining, VPA administration also obviously suppressed the ratio of Bax: Bcl-2 and the expression of cleaved caspase-3 and PARP in optic nerve in EAE rats. SIGNIFICANCE: Our findings demonstrated that VPA treatment could prevent inflammation responses and RGC apoptosis in optic nerve in EAE-ON rats, suggesting that VPA may be available for optic nerve protection during ON.