|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Engineering blood-brain barrier-permeable and tumor cell-ingestible pro-proteins for glioblastoma treatment显示文摘Intracellular protein therapeutics holds great potentials for the treatment of glioblastoma, which however, is greatly challenged by the unmet demands to concomitantly penetrate the blood-brain barrier(BBB) and glioblastoma cell membrane barrier with high efficiency and selectivity. Herein, a unique pro-protein platform was developed via facile green synthesis, which allowed efficient and selective delivery into glioblastoma cells in a carrier-free manner. Pro-proteins were engineered via reversible modification of native proteins in the aqueous buffer with 3,4-dihydroxy-phenylalanine, the substrate of L-type amino acid transporter(LAT1), bridged with a phenylboronic acid-containing linker. By harnessing the LAT1-mediated direct transport mechanism, the optimized pro-protein, named protein-M2-D, can efficiently penetrate BBB after i.v. injection, and subsequently enable selective and endocytosis-free delivery of various proteins including enzymes, toxins, and antibodies into glioblastoma cells, wherein intracellular H_(2)O_(2) triggered traceless restoration of the native protein structure. Systemic administration of saporin-M2-D provoked potent anti-tumor efficacy against orthotopic U87 glioblastoma in mice, without inducing systemic toxicity. Such a facile, versatile, and robust platform renders a promising paradigm for cytosolic protein delivery and glioblastoma treatment. | Xun Liu Wenting Si Ziyin Zhao Ningyu Liu Qiang Yang Renxiang Zhou Rongying Zhu Shanzhou Duan Yongbing Chen Lichen Yin | 2023 | Science China Chemistry2023，66，9： | 0 |
| 2 | The existence of a nonclassical TCA cycle in the nucleus that wires the metabolic-epigenetic circuitry显示文摘The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid(TCA)cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus.We report here the identification of a nonclassical TCA cycle in the nucleus(nTCA cycle).We found that all the TCA cycle-associated enzymes including citrate synthase(CS),aconitase 2(ACO2),isocitrate dehydrogenase 3(IDH3),oxoglutarate dehydrogenase(OGDH),succinyl-CoA synthetase(SCS),fumarate hydratase(FH),and malate dehydrogenase 2(MDH2),except for succinate dehydrogenase(SDH),a component of electron transport chain for generating ATP,exist in the nucleus.We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria.We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates,not for energy production.We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation.Together,our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation. | Xujun Liu Wenzhe Si Lin He Jianguo Yang Yani Peng Jie Ren Xiaoping Liu Tong Jin Huajing Yu Zihan Zhang Xiao Cheng Wenting Zhang Lu Xia Yunchao Huang Yue Wang Shumeng Liu Lin Shan Yu Zhang Xiaohan Yang Haixia Li Jing Liang Luyang Sun Yongfeng Shang | 2021 | Signal Transduction and Targeted Therapy2021，6，12： | 0 |
| 3 | Functionalization of in vivo tissue-engineered living biotubes enhance patency and endothelization without the requirement of systemic anticoagulant administration显示文摘Vascular regeneration and patency maintenance,without anticoagulant administration,represent key developmental trends to enhance small-diameter vascular grafts(SDVG)performance.In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties.However,mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs.Previously fabricated poly(ε-caprolactone)skeleton-reinforced biotubes(PBs)circumvented mechanical issues and achieved vascular regeneration,but orally administered anticoagulants were required.Here,highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens.The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(DMPE)-PEG-conjugated anti-coagulant bivalirudin(DPB)and DMPE-PEG-conjugated endothelial progenitor cell(EPC)-binding TPS-peptide(DPT)modifications possessed functionality conducive to promoting vascular graft patency.Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability.DPB repellent of non-specific proteins,DPB inhibition of thrombus formation,and DPB protection against functional masking of DPT’s EPC-capture by blood components,which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration.This strategy offers a safe,facile,and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs. | Hongyu Yan Quhan Cheng Jianghua Si Songdi Wang Ye Wan Xin Kong Ting Wang Wenting Zheng Muhammad Rafique Xiaofeng Li Ju He Adam C.Midgley Yi Zhu Kai Wang | 2023 | Bioactive Materials2023，，8： | 0 |
| 4 | Accelerated Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydride via Inorganic Nano-initiators显示文摘While the accelerated polymerization of N-carboxyanhydrides (NCAs) has been utilized to synthesize versatile polypeptide materials in an efficient manner with minimized side reactions, the preparation of polypeptide-based inorganic/organic hybrid materials with the acceleration strategy remained largely unexplored. Herein, we report the accelerated ring-opening polymerization (ROP) of NCAs mediated by amine-modified inorganic nano-initiators, such as mesoporous silica nanoparticles (MSN-NH2), which is driven by the cooperative effect of the neighboring α-helical polypeptide chains in a dichloromethane (DCM)/water biphasic system. Well-defined nano-hybrids were prepared within 15 min from non-purified NCA monomers, through in situ purification and subsequent ultrafast polymerization process. NCAs can be rapidly initiated by amino groups of MSN uniformly dispersed at the interface of DCM and water, and subsequently formed the well-defined polypeptides within 15 min. The prepared inorganic/organic nano-hybrid with MSN as the core and polypeptide as the shell adopted spherical morphology and uniform size distribution due to the excellent controllability of ROP. Besides, this system is also suitable for a variety of NCAs and inorganic nano-initiators. This research allows efficient and rapid preparation of inorganic/organic nano-hybrids, and further promotes the extensive application of this material in the biomedical fields. | Junliang Zhu Yunjie He Chenglong Ge Wenting Si Ziyuan Song Lichen Yin | 2023 | Chinese Journal of Chemistry2023，41，19： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员