耐瑞特:一种基于群体学习方法的新型硝酸盐制剂,可发挥更好的机体保护作用  

Nanonitrator:novel enhancer of inorganic nitrate’s protective effects,predicated on swarm learning approach

作　　者：潘雯 胡耿 李韶容 李国情 冯晓宇 吴志芳 张栋 秦力铮 王雪 胡亮 徐骏疾 胡磊 贾翌江 温欣 王劲松 张春梅 周建 李文斌 王晓刚 王玉记 王松灵 Wen Pan;Geng Hu;Shaorong Li;Guoqing Li;Xiaoyu Feng;Zhifang Wu;Dong Zhang;Lizheng Qin;Xue Wang;Liang Hu;Junji Xu;Lei Hu;Yijiang Jia;Xin Wen;Jinsong Wang;ChunmeZhang;Jian Zhou;Wenbin Li;Xiaogang Wang;Yuji Wang;Songlin Wang(Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction,Beijing Laboratory of Oral Health and Beijing Stomatological Hospital,Capital Medical University,Beijing 100050,China;Key Laboratory of Big Data-Based Precision Medicine,School of Engineering Medicine,Beihang University,Beijing 100191,China;Immunology Research Center for Oral and Systemic Health,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Dental Implantology,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Pediatric Dentistry,School of Stomatology,Capital Medical University,Beijing 100050,China;Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation,Beijing 100050,China;Department of Oral Maxillofacial Surgery,Capital Medical University School of Stomatology,Beijing 100050,China;School of Pharmaceutical Sciences,Capital Medical University,Beijing 100069,China;Beijing Area Major Laboratory of Peptide and Small Molecular Drugs,Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China,Beijing 100069,China;Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Laboratory for Oral and General Health Integration and Translation,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Research Units of Tooth Development and Regeneration,Chinese Academy of Medical Sciences,Beijing 100069,China)

机构地区：[1]Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction,Beijing Laboratory of Oral Health and Beijing Stomatological Hospital,Capital Medical University [2]Key Laboratory of Big Data-Based Precision Medicine,School of Engineering Medicine,Beihang University [3]Immunology Research Center for Oral and Systemic Health,Beijing Friendship Hospital,Capital Medical University [4]Department of Dental Implantology,The Affiliated Stomatological Hospital of Nanjing Medical University [5]Department of Pediatric Dentistry,School of Stomatology,Capital Medical University [6]Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation [7]Department of Oral Maxillofacial Surgery,Capital Medical University School of Stomatology [8]School of Pharmaceutical Sciences,Capital Medical University [9]Beijing Area Major Laboratory of Peptide and Small Molecular Drugs,Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China1 [10]Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Capital Medical University1 [11]Laboratory for Oral and General Health Integration and Translation,Beijing Tiantan Hospital,Capital Medical University1 [12]Research Units of Tooth Development and Regeneration,Chinese Academy of Medical Sciences

出　　处：《Science Bulletin》2023年第8期838-850,M0004,共14页科学通报（英文版）

基　　金：supported by the Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226000041);the Beijing Municipal Science and Technology Commission(Z181100001718208);the Beijing Municipal Education Commission(119207020201);the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201);the Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5031);the National Natural Science Foundation of China(92049201,82030031,81991504,and 92149301);the Beijing Advanced Innovation Center for Big Data-based Precision Medicine(PXM2021_014226_000026);the Beijing Municipal Government(Beijing Scholar Program,PXM2020_014226_000005 and PXM2021_014226_000020);the Beijing Municipal Colleges and Universities High Level Talents Introduction and Cultivate Project-Beijing Great Wall Scholar Program(CIT&TCD 20180332);the National Key Research and development Program(2022YFA1104401)。

摘　　要：硝酸盐是一种机体不可或缺的营养物质,已应用于多种疾病的预防和治疗研究.但由于半衰期短,硝酸盐的临床应用受限.为了提高硝酸盐可用性,突破传统的依赖大规模高通量生物实验的药物配伍研发瓶颈,本文报道了一种基于群体学习方法的药物配伍预测系统,该系统预测维生素C为与硝酸盐配伍的首选药物.通过采用微囊化技术,筛选并优化缓释制剂工艺,以维生素C、硝酸钠及壳聚糖3000为芯材,果胶与羧甲基纤维素钠为壁材制备硝酸盐纳米颗粒,命名为耐瑞特(Nanonitrator).耐瑞特的更长循环期显著提高了硝酸盐对放射性唾液腺损伤的疗效,同时维持了安全性.相同剂量的耐瑞特比硝酸盐(包含或不包含维生素C)可显著增强PI3K-Akt信号通路转导,更好地维持细胞内稳态,提示了其广泛的临床应用潜力.此外,本文还提供了一种将无机化合物加入缓释纳米颗粒的新方法.Inorganic nitrate is an indispensable nutrient that has been used in experimental studies for the prevention and treatment of several diseases.However,the short half-life of nitrate limits its clinical application.To increase the usability of nitrate and overcome the challenges of traditional combination drug discovery through large-scale high-throughput biological experiments,we developed a swarm learning-based combination drug prediction system that identified vitamin C as the drug of choice to be combined with nitrate.Employing microencapsulation technology,we used vitamin C,sodium nitrate,and chitosan 3000 as the core materials to prepare a nitrate nanoparticle,which we named Nanonitrator.The longcirculating delivery ability of nitrate by Nanonitrator significantly increased the efficacy and effect duration of nitrate in irradiation-induced salivary gland injury,without compromising safety.Nanonitrator at the same dose could better maintain intracellular homeostasis than nitrate(with or without vitamin C),emphasizing its potential for clinical use.More importantly,our work provides a method for incorporating inorganic compounds into sustained-release nanoparticles.

关 键 词：Inorganic nitrate Artificial intelligence NANOMEDICINE CHITOSAN Irradiation-induced submandibular gland INJURY HOMEOSTASIS 

分 类 号：TQ460.1[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程]