• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

重新思考脑靶向药物递送的 CRITID 程序：循环、血脑屏障识别、细胞内转运、病变细胞靶向、内化和药物释放。

Rethinking CRITID Procedure of Brain Targeting Drug Delivery: Circulation, Blood Brain Barrier Recognition, Intracellular Transport, Diseased Cell Targeting, Internalization, and Drug Release.

机构信息

Key laboratory of Drug Targeting and Drug Delivery Systems of the Education Ministry Sichuan Engineering Laboratory for Plant-sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University Chengdu 610041 China.

Department of Pharmaceutics College of Pharmacy University of Florida Gainesville Florida 32610 USA.

出版信息

Adv Sci (Weinh). 2021 Feb 24;8(9):2004025. doi: 10.1002/advs.202004025. eCollection 2021 May.

DOI:10.1002/advs.202004025
PMID:33977060
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8097396/
Abstract

The past decades have witnessed great progress in nanoparticle (NP)-based brain-targeting drug delivery systems, while their therapeutic potentials are yet to be fully exploited given that the majority of them are lost during the delivery process. Rational design of brain-targeting drug delivery systems requires a deep understanding of the entire delivery process along with the issues that they may encounter. Herein, this review first analyzes the typical delivery process of a systemically administrated NPs-based brain-targeting drug delivery system and proposes a six-step CRITID delivery cascade: circulation in systemic blood, recognizing receptor on blood-brain barrier (BBB), intracellular transport, diseased cell targeting after entering into parenchyma, internalization by diseased cells, and finally intracellular drug release. By dissecting the entire delivery process into six steps, this review seeks to provide a deep understanding of the issues that may restrict the delivery efficiency of brain-targeting drug delivery systems as well as the specific requirements that may guarantee minimal loss at each step. Currently developed strategies used for troubleshooting these issues are reviewed and some state-of-the-art design features meeting these requirements are highlighted. The CRITID delivery cascade can serve as a guideline for designing more efficient and specific brain-targeting drug delivery systems.

摘要

过去几十年见证了基于纳米颗粒 (NP) 的脑靶向药物传递系统的巨大进展，但由于大多数 NP 在传递过程中丢失，它们的治疗潜力尚未得到充分利用。脑靶向药物传递系统的合理设计需要深入了解整个传递过程以及它们可能遇到的问题。在此，本文首先分析了系统给药的 NPs 基脑靶向药物传递系统的典型传递过程，并提出了一个六步 CRITID 传递级联：系统血液中的循环、血脑屏障 (BBB) 上的识别受体、细胞内转运、进入实质后的病变细胞靶向、病变细胞的内化，以及最终的细胞内药物释放。通过将整个传递过程分解成六个步骤，本文旨在深入了解可能限制脑靶向药物传递系统传递效率的问题以及可能保证每个步骤最小损失的具体要求。目前用于解决这些问题的开发策略进行了回顾，并突出了满足这些要求的一些最先进的设计特点。CRITID 传递级联可作为设计更高效和更具特异性的脑靶向药物传递系统的指南。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/9625a6c5ba52/ADVS-8-2004025-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/1844c372dab2/ADVS-8-2004025-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/840d713b068b/ADVS-8-2004025-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/852ef57b2855/ADVS-8-2004025-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/107859b6f27c/ADVS-8-2004025-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/ca08ac28c1b4/ADVS-8-2004025-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/488ff3436a61/ADVS-8-2004025-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/71dec3d6d5fe/ADVS-8-2004025-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/602cc3de8828/ADVS-8-2004025-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/c8fe42d62ab4/ADVS-8-2004025-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/5e1d62c65bd4/ADVS-8-2004025-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/051497210eae/ADVS-8-2004025-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/9625a6c5ba52/ADVS-8-2004025-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/1844c372dab2/ADVS-8-2004025-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/840d713b068b/ADVS-8-2004025-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/852ef57b2855/ADVS-8-2004025-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/107859b6f27c/ADVS-8-2004025-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/ca08ac28c1b4/ADVS-8-2004025-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/488ff3436a61/ADVS-8-2004025-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/71dec3d6d5fe/ADVS-8-2004025-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/602cc3de8828/ADVS-8-2004025-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/c8fe42d62ab4/ADVS-8-2004025-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/5e1d62c65bd4/ADVS-8-2004025-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/051497210eae/ADVS-8-2004025-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e7/8097396/9625a6c5ba52/ADVS-8-2004025-g005.jpg

相似文献

1
Rethinking CRITID Procedure of Brain Targeting Drug Delivery: Circulation, Blood Brain Barrier Recognition, Intracellular Transport, Diseased Cell Targeting, Internalization, and Drug Release.重新思考脑靶向药物递送的 CRITID 程序：循环、血脑屏障识别、细胞内转运、病变细胞靶向、内化和药物释放。
Adv Sci (Weinh). 2021 Feb 24;8(9):2004025. doi: 10.1002/advs.202004025. eCollection 2021 May.
2
Perspectives on Dual Targeting Delivery Systems for Brain Tumors.脑肿瘤双重靶向递药系统的研究进展。
J Neuroimmune Pharmacol. 2017 Mar;12(1):6-16. doi: 10.1007/s11481-016-9687-4. Epub 2016 Jun 8.
3
Recent expansions of novel strategies towards the drug targeting into the brain.新型药物靶向脑部策略的最新进展。
Int J Nanomedicine. 2019 Jul 30;14:5895-5909. doi: 10.2147/IJN.S210876. eCollection 2019.
4
Strategies to improve drug delivery across the blood-brain barrier.改善药物透过血脑屏障递送的策略。
Clin Pharmacokinet. 2007;46(7):553-76. doi: 10.2165/00003088-200746070-00002.
5
Nanoparticle technology for drug delivery across the blood-brain barrier.用于跨越血脑屏障进行药物递送的纳米颗粒技术
Drug Dev Ind Pharm. 2002 Jan;28(1):1-13. doi: 10.1081/ddc-120001481.
6
Central nervous system delivery of molecules across the blood-brain barrier.分子经血脑屏障的中枢神经系统递释。
Neurochem Int. 2021 Mar;144:104952. doi: 10.1016/j.neuint.2020.104952. Epub 2021 Jan 2.
7
Targeting the transferrin receptor for brain drug delivery.针对脑内药物递送的转铁蛋白受体。
Prog Neurobiol. 2019 Oct;181:101665. doi: 10.1016/j.pneurobio.2019.101665. Epub 2019 Jul 31.
8
Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection.用于中枢神经系统感染治疗药物递送的可生物降解纳米颗粒
J Neuroimmune Pharmacol. 2017 Mar;12(1):31-50. doi: 10.1007/s11481-016-9692-7. Epub 2016 Jul 2.
9
Designing peptide nanoparticles for efficient brain delivery.设计用于高效脑递送的肽纳米粒。
Adv Drug Deliv Rev. 2020;160:52-77. doi: 10.1016/j.addr.2020.10.001. Epub 2020 Oct 5.
10
Recent progress of drug nanoformulations targeting to brain.针对脑部的药物纳米制剂的最新进展。
J Control Release. 2018 Dec 10;291:37-64. doi: 10.1016/j.jconrel.2018.10.004. Epub 2018 Oct 9.

引用本文的文献

1
Stimuli-Responsive, Cell-Mediated Drug Delivery Systems: Engineering Smart Cellular Vehicles for Precision Therapeutics.刺激响应型细胞介导药物递送系统：构建用于精准治疗的智能细胞载体
Pharmaceutics. 2025 Aug 21;17(8):1082. doi: 10.3390/pharmaceutics17081082.
2
Lipid nanoparticles for mRNA delivery in brain via systemic administration.通过全身给药用于脑内mRNA递送的脂质纳米颗粒。
Sci Adv. 2025 Aug 15;11(33):eadw0730. doi: 10.1126/sciadv.adw0730. Epub 2025 Aug 13.
3
All-in-one peptide with sequential pH gradient sensing capabilities for the targeted delivery and deep penetration of nanomicelles against breast cancer.

本文引用的文献

1
Dual-targeting nanovesicles enhance specificity to dynamic tumor cells and manipulation of v3-ligand binding.双靶向纳米囊泡增强了对动态肿瘤细胞的特异性以及对v3配体结合的操控。
Acta Pharm Sin B. 2020 Nov;10(11):2183-2197. doi: 10.1016/j.apsb.2020.07.012. Epub 2020 Jul 25.
2
The progress and perspective of nanoparticle-enabled tumor metastasis treatment.纳米颗粒介导的肿瘤转移治疗的进展与展望
Acta Pharm Sin B. 2020 Nov;10(11):2037-2053. doi: 10.1016/j.apsb.2020.07.013. Epub 2020 Jul 26.
3
Charge Conversional Biomimetic Nanocomplexes as a Multifunctional Platform for Boosting Orthotopic Glioblastoma RNAi Therapy.
具有连续pH梯度传感能力的一体化肽，用于纳米胶束对乳腺癌的靶向递送和深度渗透。
Asian J Pharm Sci. 2025 Aug;20(4):101056. doi: 10.1016/j.ajps.2025.101056. Epub 2025 Apr 18.
4
Nanoparticles for Glioblastoma Treatment.用于治疗胶质母细胞瘤的纳米颗粒
Pharmaceutics. 2025 May 23;17(6):688. doi: 10.3390/pharmaceutics17060688.
5
Carbon Dots Extracted from the Plant Ameliorates Ischemia-Reperfusion Injury.从植物中提取的碳点可改善缺血再灌注损伤。
Pharmaceuticals (Basel). 2025 Jun 11;18(6):870. doi: 10.3390/ph18060870.
6
Engineered brain-targeting exosome for reprogramming immunosuppressive microenvironment of glioblastoma.工程化脑靶向外泌体用于重编程胶质母细胞瘤的免疫抑制微环境
Exploration (Beijing). 2024 Jun 26;5(2):20240039. doi: 10.1002/EXP.20240039. eCollection 2025 Apr.
7
Nano-Encapsulated Taro Lectin Can Cross an in vitro Blood-Brain Barrier, Induce Apoptosis and Autophagy and Inhibit the Migration of Human U-87 MG Glioblastoma Cells.纳米封装的芋头凝集素可穿过体外血脑屏障，诱导细胞凋亡和自噬，并抑制人U-87 MG胶质母细胞瘤细胞的迁移。
Int J Nanomedicine. 2025 Apr 29;20:5573-5591. doi: 10.2147/IJN.S511506. eCollection 2025.
8
Trojan Horse Delivery Strategies of Natural Medicine Monomers: Challenges and Limitations in Improving Brain Targeting.天然药物单体的“特洛伊木马”递送策略：改善脑靶向性面临的挑战与局限
Pharmaceutics. 2025 Feb 20;17(3):280. doi: 10.3390/pharmaceutics17030280.
9
Novel AP39-Loaded Liposomes Sustain the Release of Hydrogen Sulphide, Enhance Blood-Brain Barrier Permeation, and Abrogate Oxidative Stress-Induced Mitochondrial Dysfunction in Brain Cells.新型载有AP39的脂质体可维持硫化氢的释放，增强血脑屏障通透性，并消除氧化应激诱导的脑细胞线粒体功能障碍。
Drug Des Devel Ther. 2025 Mar 19;19:2067-2079. doi: 10.2147/DDDT.S507697. eCollection 2025.
10
Nebulized seabuckthorn seed oil inhalation attenuates Alzheimer's disease progression in APP/PS1 mice.雾化沙棘籽油吸入可减缓APP/PS1小鼠的阿尔茨海默病进展。
Sci Rep. 2025 Feb 21;15(1):6368. doi: 10.1038/s41598-025-89747-x.
电荷转换仿生纳米复合物作为一种多功能平台，用于增强原位脑胶质瘤 RNAi 治疗。
Nano Lett. 2020 Mar 11;20(3):1637-1646. doi: 10.1021/acs.nanolett.9b04683. Epub 2020 Feb 7.
4
Enhanced in Vivo Blood-Brain Barrier Penetration by Circular Tau-Transferrin Receptor Bifunctional Aptamer for Tauopathy Therapy.环状 Tau-转铁蛋白受体双功能适体增强 Tau 病治疗的血脑屏障穿透性。
J Am Chem Soc. 2020 Feb 26;142(8):3862-3872. doi: 10.1021/jacs.9b11490. Epub 2020 Feb 11.
5
Bioinspired Nanosponge for Salvaging Ischemic Stroke via Free Radical Scavenging and Self-Adapted Oxygen Regulating.用于通过自由基清除和自适应氧调节挽救缺血性中风的仿生纳米海绵
Nano Lett. 2020 Jan 8;20(1):780-789. doi: 10.1021/acs.nanolett.9b04974. Epub 2019 Dec 16.
6
Dual and multi-targeted nanoparticles for site-specific brain drug delivery.用于特定部位脑内药物递送的双靶和多靶纳米粒
J Control Release. 2020 Jan 10;317:195-215. doi: 10.1016/j.jconrel.2019.11.037. Epub 2019 Nov 30.
7
First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound.人血液脑屏障开放在肌萎缩侧索硬化症的初步临床试验使用磁共振引导聚焦超声。
Nat Commun. 2019 Sep 26;10(1):4373. doi: 10.1038/s41467-019-12426-9.
8
Tumor-Derived Extracellular Vesicles Breach the Intact Blood-Brain Barrier Transcytosis.肿瘤细胞外囊泡穿透完整的血脑屏障 胞吞作用。
ACS Nano. 2019 Dec 24;13(12):13853-13865. doi: 10.1021/acsnano.9b04397. Epub 2019 Sep 10.
9
Brain-targeted drug delivery by manipulating protein corona functions.通过操纵蛋白冠功能实现脑靶向药物递送。
Nat Commun. 2019 Aug 8;10(1):3561. doi: 10.1038/s41467-019-11593-z.
10
CAR T cells for brain tumors: Lessons learned and road ahead.嵌合抗原受体 T 细胞治疗脑肿瘤：经验教训与未来展望。
Immunol Rev. 2019 Jul;290(1):60-84. doi: 10.1111/imr.12773.