A drug delivery system constructed by a fusion peptide capturing exosomes targets to titanium implants accurately resulting the enhancement of osseointegration peri-implant

Li Xuewen,Liu Zihao,Xu Shendan,Ma Xinying,Zhao Zhezhe,Hu Han,Deng Jiayin,Peng Cheng,Wang Yonglan,Ma Shiqing 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs, but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient’s body and expected to find a method to treat implant with BMSC-exos in vivo directly.A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface.Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy.This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.

Microstructural Characterization and Softening Mechanism of Ultra-Low Carbon Steel and the Control Strategy in Compact Strip Production Process

Bo Jiang,Xuewen Hu,Guoning He,Huan Peng,Haibo Wang,Yazheng Liu 대한금속·재료학회 2020 METALS AND MATERIALS International Vol.26 No.9

In this paper, the microstructures and properties of hot rolled ultra-low carbon steel sheet produced by different compact stripproduction (CSP) processes were investigated. The softening mechanism was also discussed and the control strategy wasproposed in order to obtain optimum properties. Result showed that the average ferrite grain sizes of austenite rolling sheetand multiphase rolling sheet were 31.0 μm and 74.6 μm, respectively. The sheet after austenite rolling had a slightly higheryield and tensile strength while had a 6.3% higher elongation than that of the sheet after multiphase rolling. The higher dislocationin the sheet after multiphase rolling increased the strength while decreased the elongation. The softening mechanismof the sheet after multiphase rolling was the coarsening of ferrite grain. The combined role of {001} and {111} orientationresulted in a slight increase of the r and ̄rvalue in the sheet after multiphase rolling. It was a wise choice to conduct rollingat the Ac1temperature in CSP process to increase the grain size and decrease the dislocation density. Then, the strength ofthe sheets could be further reduced and the elongation could also be improved.

Effect of Transformation Temperature on the Ferrite–Bainite Microstructures, Mechanical Properties and the Deformation Behavior in a Hot-Rolled Dual Phase Steel

Bo Jiang,Xuewen Hu,Leyu Zhou,Haibo Wang,Yazheng Liu,Fugang Gou 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.2

The ferrite–bainite microstructures and mechanical properties in a hot-rolled dual phase steel with different transformationtemperatures were investigated in this paper. The deformation behavior of bainite and ferrite was analyzed by using in situscanning electron microscope. The results showed that the ferrite and bainite can be refined and the volume fraction of bainitecan be slightly increased by 5% by decreasing the ferrite transformation temperature from 690 to 635 °C and increasing thebainite transformation temperature from 400 to 450 °C. The strengthening mechanism was dislocation difference in polygonaland acicular ferrite and then the grain size difference of ferrite. The hole expansion ratio increased from 52.9 to 83.7% withthe ferrite transformation temperature decreasing. The cracks or voids were smaller in size and also the number in steel withthe lower ferrite transformation temperature after expanding. The microstructure separation along the boundary betweenbainite and ferrite and the slip band in the ferrite appeared at the non-uniform deformation stage. However, fewer appearedin the microstructure of steel with lower ferrite transformation temperature. Cooperative deformation of ferrite and bainiteand finer microstructure in steel with lower ferrite transformation temperature were the mechanisms why the cracks couldnot easily nucleated and propagated, respectively. Thus this was also why there was a better hole expansion ratio.

Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

Xiang Wei,Peng Yongbo,Zeng Hongliang,Yu Chunping,Zhang Qun,Liu Biao,Liu Jiahao,Hu Xing,Wei Wensu,Deng Minhua,Wang Ning,Liu Xuewen,Xie Jianfei,Hou Weibin,Tang Jin,Long Zhi,Wang Long,Liu Jianye 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA

Chunping Yu,Yi Zhang,Ning Wang,Wensu Wei,Ke Cao,Qun Zhang,Peiying Ma,Dan Xie,Pei Wu,Biao Liu,Jiahao Liu,Wei Xiang,Xing Hu,Xuewen Liu,Jianfei Xie,Jin Tang,Zhi Long,Long Wang,Hongliang Zeng,Jianye Liu 한국생체재료학회 2022 생체재료학회지 Vol.26 No.1

Background: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. Methods: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. Results: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5’s half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/sicircPRMT5 regulated the miR-30c/SNAIL1/E-adherin axis, inhibiting bladder cancer growth and progression. Conclusion: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.