Advances in pharmacology最新文献_第2页

Chemically enhanced brain shuttle peptides. 化学增强脑穿梭肽。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-02-25 DOI: 10.1016/bs.apha.2026.02.003

Cristina Díaz-Perlas

{"title":"Chemically enhanced brain shuttle peptides.","authors":"Cristina Díaz-Perlas","doi":"10.1016/bs.apha.2026.02.003","DOIUrl":"10.1016/bs.apha.2026.02.003","url":null,"abstract":"The blood-brain barrier (BBB) constitutes a major impediment to central nervous system pharmacotherapy due to its highly selective permeability and enzymatic defense mechanisms. Brain shuttle peptides have emerged as a promising modality for overcoming this barrier, primarily via receptor-mediated transcytosis. To enhance their pharmacokinetic properties and transcytosis efficiency, several structural and chemical optimization strategies have been employed. Cyclization and retro-enantio modifications confer proteolytic resistance while preserving receptor affinity, as demonstrated by engineered peptides such as retro-D-THR, retro-D-T7, and BB4. Venom-derived scaffolds, including MiniAp-4 and MiniCTX3, further exemplify the potential of naturally occurring peptides for BBB penetration. Multivalent presentation, achieved through branched architectures or nanoparticle surface functionalization, significantly increases avidity and cellular uptake, thereby improving transcytosis. Dual-ligand systems, such as THR-TAT conjugates, have shown synergistic effects in glioma models, enhancing both BBB crossing and tumor targeting. While PEGylation is widely utilized in drug delivery to prolong circulation and reduce immunogenicity, its application in brain shuttle systems remains limited due to potential interference with receptor-mediated uptake. Collectively, these advances underscore the versatility of protease-resssistant brain shuttle peptides as targeted delivery vehicles for CNS therapeutics and provide a strong foundation for their translation into clinical applications.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"105 ","pages":"133-170"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain shuttle peptides derived from phage display. 来自噬菌体展示的脑穿梭肽。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-03-09 DOI: 10.1016/bs.apha.2026.02.001

Alexander M Ille, Fenny H F Tang, Ethan R Chen, Wadih Arap, Renata Pasqualini

引用次数: 0

Brain shuttle peptides: From permeability assay toolbox to data-driven discovery. 脑穿梭肽：从渗透性分析工具箱到数据驱动的发现。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-03-14 DOI: 10.1016/bs.apha.2026.02.002

Nikolina Mohović, Marko Njirjak, Ena Dražić, Patrizia Janković Bevandić, Daniela Kalafatovic

{"title":"Brain shuttle peptides: From permeability assay toolbox to data-driven discovery.","authors":"Nikolina Mohović, Marko Njirjak, Ena Dražić, Patrizia Janković Bevandić, Daniela Kalafatovic","doi":"10.1016/bs.apha.2026.02.002","DOIUrl":"10.1016/bs.apha.2026.02.002","url":null,"abstract":"The blood-brain barrier (BBB) is a highly selective transport interface that protects the central nervous system (CNS), but its complex cellular and molecular architecture presents a major challenge for drug delivery to the brain. Peptides have emerged as promising brain shuttles due to their selectivity, ease of synthesis, and ability to engage endogenous transport mechanisms such as receptor- or adsorptive-mediated transcytosis. We provide an overview of in vitro and in vivo models, ranging from artificial membranes, dynamic BBB-on-a-chip systems and mass-based quantification techniques to brain perfusion and molecular imaging. Particular emphasis is placed on how these approaches are selected and combined to assess BBB permeability, transport mechanisms, and brain distribution of peptide shuttles. Recently, machine learning methods have been increasingly used to identify peptide sequences with BBB-crossing potential. By highlighting recent examples and key methodological considerations, this chapter aims to guide researchers in selecting appropriate tools and strategies for studying peptide transport across the BBB.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"105 ","pages":"99-131"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T Cell subsets for therapy-unconventional CD1d-restricted natural killer T cells. 用于治疗的T细胞亚群——非常规cd1限制性自然杀伤T细胞。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-05-21 DOI: 10.1016/bs.apha.2026.05.006

Monika Holubová, Valentina Sofia Caputo Galarce, Miroslava Čedíková

{"title":"T Cell subsets for therapy-unconventional CD1d-restricted natural killer T cells.","authors":"Monika Holubová, Valentina Sofia Caputo Galarce, Miroslava Čedíková","doi":"10.1016/bs.apha.2026.05.006","DOIUrl":"https://doi.org/10.1016/bs.apha.2026.05.006","url":null,"abstract":"Unconventional T cells, including gamma delta (γδ) T cells, mucosal-associated invariant T (MAIT) cells, and CD1d-restricted natural killer T (NKT) cells, comprise a unique component of the immune system. These cells play critical roles in host defense, immune regulation, and disease pathogenesis. In particular, invariant NKT (iNKT) cells have emerged as key immunological orchestrators that bridge innate and adaptive immunity by rapidly recognizing lipid antigens presented by CD1d molecules. This chapter provides a comprehensive overview of iNKT cell biology, including their development, phenotypic and functional heterogeneity, and activation mechanisms. It discusses the role of iNKT cells in pathological conditions in detail. Their ability to directly kill tumor cells, as well as their potential to orchestrate the immune response, opens up new possibilities for anti-cancer therapy. Their contribution to immune response regulation and tolerance highlights their critical role in infectious diseases and transplantation. The chapter summarizes current clinical approaches aimed at harnessing iNKT cells, including in vivo activation strategies, adoptive transfer of ex vivo-expanded cells, and developing chimeric antigen receptor (CAR)-engineered iNKT cells. These emerging therapies have advantages over conventional CAR-T approaches, such as reduced toxicity and the potential for allogeneic use. Finally, the chapter discusses the role of type II NKT cells and their cross-regulatory interactions with iNKT cells. Overall, CD1d-restricted NKT cells are a promising target for next-generation immunotherapies. However, further mechanistic and clinical studies are needed to realize their full therapeutic potential.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"106 ","pages":"65-99"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preface. 前言。

Advances in pharmacology Pub Date : 2026-01-01 DOI: 10.1016/S1054-3589(26)00065-7

引用次数: 0

Functionalization of inorganic nanoparticles with peptides to cross the blood brain barrier: In vivo evaluation. 带肽的无机纳米颗粒功能化以穿越血脑屏障：体内评价。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-03-12 DOI: 10.1016/bs.apha.2026.02.004

Blanca Isart, Aurora J Araya-Vergara, Ana Riveros, Marcelo J Kogan

引用次数: 0

Polymeric nanoparticles functionalized with peptides: Advanced strategies for crossing the blood-brain barrier. 多肽功能化聚合纳米颗粒：跨越血脑屏障的先进策略。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-04-24 DOI: 10.1016/bs.apha.2026.03.002

X Llorente, G Esteruelas, M L García, E B Souto, E Sánchez-López

{"title":"Polymeric nanoparticles functionalized with peptides: Advanced strategies for crossing the blood-brain barrier.","authors":"X Llorente, G Esteruelas, M L García, E B Souto, E Sánchez-López","doi":"10.1016/bs.apha.2026.03.002","DOIUrl":"10.1016/bs.apha.2026.03.002","url":null,"abstract":"Targeted drug delivery to the central nervous system (CNS) to tackle brain disorders is hindered by the blood-brain barrier (BBB) which, due to its unique physiology, severely restricts the entry of drugs into the brain. Among the different strategies proposed to overcome the BBB, nanotechnology-based approaches, particularly polymeric nanoparticles (PNPs), have emerged as promising tools. These carriers can protect therapeutic payloads, modulate release profiles, and enhance drug concentration in the CNS. Furthermore, their surfaces can be functionalized with brain shuttle peptides for active targeting strategies. Peptide shuttles recognize specific receptors on the cerebral endothelium, thereby promoting transcytosis and facilitating selective transport into the brain. Peptides functionalizing the surface of PNPs may also increase the interactions between these PNPs and lipid bilayers thereby improving their penetration across the BBB. This chapter discusses the properties and design of peptide-functionalized PNPs, emphasizing how particle size, surface and biodegradability critically influence their performance. Chemical conjugation methods enabling the stable attachment of peptide shuttles are discussed, with particular attention to translational studies addressing major CNS pathologies, including brain tumors, neurodegenerative diseases, and ischemic injuries. Current challenges that determine clinical application, such as variability in synthesis, toxicity, and enzymatic instability, are also critically analysed with the aim of outlining future directions for peptide-mediated drug delivery to the brain.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"105 ","pages":"325-363"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain delivery of lipid nanoparticles with shuttle peptides. 带穿梭肽的脂质纳米颗粒的脑递送。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-03-07 DOI: 10.1016/bs.apha.2026.02.005

Noelia Martinez-Martinez, Laura Carrera-Rodríguez, Ronny Vargas, Cristina Hernández-Munain, Marc Suñé-Pou, Carles Suñé

{"title":"Brain delivery of lipid nanoparticles with shuttle peptides.","authors":"Noelia Martinez-Martinez, Laura Carrera-Rodríguez, Ronny Vargas, Cristina Hernández-Munain, Marc Suñé-Pou, Carles Suñé","doi":"10.1016/bs.apha.2026.02.005","DOIUrl":"10.1016/bs.apha.2026.02.005","url":null,"abstract":"Lipid nanoparticles (LNPs) have gained growing attention as advanced drug delivery systems capable of addressing major challenges in the development of innovative therapies. They have been widely investigated to overcome the challenges of development delivery strategies for the Central Nervous System (CNS). Their small size, biomimetic lipid composition, and modifiable surface properties make them promising candidates for targeting the Blood Brain Barrier (BBB), leading to improved therapeutic interventions. This chapter provides an integrative overview of the main classes of LNPs and their manufacturing methods, offering insights into their design, characterization, and optimization for brain delivery. We first discuss the key physicochemical parameters -particle size, polydispersity index, surface charge, shape, crystallinity, and encapsulation efficiency- and their impact on biodistribution, stability, and BBB penetration. Formulation and manufacturing strategies are examined, from conventional approaches to microfluidic mixing. Special attention is given to surface modification strategies, including ligand conjugation and the technological variables influencing receptor-specific transport that determine brain targeting. We place particular emphasis on brain-shuttle peptides, which constitute the most widely employed approach for functionalizing LNPs. Finally, we summarize representative preclinical studies, emerging clinical trials, and key translational challenges -such as neurotoxicity, batch-to-batch reproducibility, and regulatory hurdles-, but also highlight the proved potential of LNPs to achieve successful clinical translation in other therapeutic areas. These advances provide valuable insights and technical precedents that may benefit the development of LNP-based therapeutics for CNS disorders, supporting future strategies targeting neurological and psychiatric disorders as well as brain tumors.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"105 ","pages":"257-323"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing the persistence of therapeutic T cells. 增强治疗性T细胞的持久性。

Advances in pharmacology Pub Date : 2026-01-01 Epub Date: 2026-06-08 DOI: 10.1016/bs.apha.2026.05.008

Gregory M Chen, Joseph A Fraietta

引用次数: 0

Preface. 前言。

Advances in pharmacology Pub Date : 2026-01-01 DOI: 10.1016/S1054-3589(26)00045-1

Macarena Sánchez-Navarro, Benjamí Oller-Salvia

引用次数: 0