Delivery of Biomimetic Liposomes via Meningeal Lymphatic Vessels Route for Targeted Therapy of Parkinson’s Disease

Targeted therapy of Parkinson’s disease is an important challenge because of the blood–brain barrier limitation.Here,we propose a natural killer cell membrane biomimetic nanocomplex(named BLIPO-CUR)delivered via the meningeal lymphatic vessel(MLV)route to further the therapeutic efficacy of Parkinson’s disease.The membrane incorporation enables BLIPO-CUR to target the damaged neurons,thus improving their therapeutic efficacy through clearing reactive oxygen species,suppressing the aggregation ofα-synuclein,and inhibiting the spread of excessα-synuclein species.Compared with the conventional intravenous injection,this MLV administration can enhance the delivered efficiency of curcumin into the brain by~20 folds.The MLV route administration of BLIPO-CUR enhances the treatment efficacy of Parkinson’s disease in mouse models by improving their movement disorders and reversing neuron death.Our findings highlight the great potential of MLV route administration used as targeted delivery of drugs to the brain,holding a great promise for neurodegenerative disease therapy.

近红外二区荧光可视化超声联合吲哚菁绿微泡开放血脑屏障增强脑胶质瘤光热治疗

聚焦超声开放血脑屏障是增强胶质母细胞瘤治疗的关键,然而,缺乏一种高时空分辨率的体内成像方法用于原位同步监测血脑屏障开放过程.本文报道了使用吲哚菁绿掺杂的微泡(MBs-ICG)可视化聚焦超声开放血脑屏障和增强对抗胶质母细胞瘤的光热治疗方法.结果显示, MBs-ICG具有明亮的近红外二区荧光,超声造影成像和超声响应特性.利用其互补的成像特性, MBs-ICG可实现脑血管的高分辨率(~168.9μm)近红外二区荧光成像、大穿透深度(~7 mm)超声造影成像.通过近红外二区荧光成像, MBs-ICG联合聚焦超声可原位同步可视化血脑屏障开放,信噪比为6.2±1.2.此外,在聚焦超声辐照下, MBs-ICG转化为脂质ICG纳米颗粒,并在10 min内迅速进入肿瘤组织,成功用于增强原位胶质母细胞瘤小鼠的光热治疗.多功能MBs-ICG为监测血脑屏障开放和增强胶质母细胞瘤治疗提供了一种新的范式.

超小二维硅量子片:一种用于脑胶质瘤原位诊疗的脑部光热纳米制剂

提出了一种化学脱嵌和低温辅助剥离相结合的策略用于制备二维硅量子片(silicon quantum sheets,Si QSs),并证实了硅量子片能够用作高性能光热纳米制剂,在恶性程度极高的脑胶质瘤诊断和治疗上有很好的应用前景.本文制备的硅量子片横向尺寸约为14.0 nm,厚度约为1.6 nm,质量消光系数和光热转换效率分别为27.5 g^(-1)cm^(-1)和47.2%,光热性能优于目前所报道的其他单元素二维材料.经尾静脉注射后,硅量子片可穿透血脑肿瘤屏障,在脑胶质瘤组织中有效蓄积,显著增强肿瘤区域的光声信号,实现了近红外光驱动的脑肿瘤靶向治疗.经激光照射5 min后,实验组小鼠的脑胶质瘤能得到有效抑制,小鼠生存期延长了1倍.该项工作拓展了二维硅在脑疾病治疗中的生物医学应用.

Centimeter-Deep NIR-II Fluorescence Imaging with Nontoxic AIE Probes in Nonhuman Primates

Fluorescence probes with aggregation-induced emission(AIE)characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution.However,the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical translation.Here,we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green(ICG)during a study period of 36 days to demonstrate AIE probes are nontoxic.Furthermore,through bright and nontoxic AIE probes and fluorescence imaging in the second window(NIR-II,1,000-1,700 nm),we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates,breaking the current limitation of millimeter-deep NIR-II fluorescence imaging.Our important findings,i.e.,nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates,may facilitate successful translation of AIE probes in clinical trials.

A PIID-DTBT based semi-conducting polymer dots with broad and strong optical absorption in the visible-light region： Highly effective contrast agents for multiscale and multi-spectral photoacoustic imaging

As a hybrid imaging technique, photoacoustic imaging （PAI） can provide multiscale morphological information of tissues, and the use of multi-spectral PAI （MSPAI） can recover the spatial distribution of chromophores of interest, such as hemoglobin within tissues. Herein, we developed a contrast agent that can very effectively combine multiscale PAI with MSPAI for a more comprehensive characterization of complex biological tissues. Specifically, we developed novel PIID-DTBT based semi-conducting polymer dots （Pdots） that show broad and strong optical absorption in the visible-light region （500-700 nm）. The performances of gold nanoparticles （GNPs） and gold nanorods （GNRs）, which have been verified as excellent photoacoustic contrast agents, were compared with that of the Pdots based on the multiscale PAI system. Both ex vivo and in vivo experiments demonstrated that the Pdots have better photoacoustic conversion efficiency at 532 nm than GNPs and showed similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Photostability and toxicity tests demonstrated that the Pdots are photostable and biocompatible. More importantly, an in vivo MSPAI experiment indicated that the Pdots have better photoacoustic performance than the blood and therefore the signals can be accurately extracted from the background of vascular-rich tissues. Our work demonstrates the great potential of Pdots as highly effective contrast agents for the precise localization of lesions relative to the blood vessels based on multiscale PAI and MSPAI.