Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier

Abstract The blood-brain barrier (BBB) poses a major challenge to the effective delivery of therapeutic agents for the treatment of central nervous system (CNS) disorders. The integration of cell membrane engineering with nanotechnology has recently enabled the development of membrane-engineered nan...

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Main Authors: Shengnan Yuan, Dehong Hu, Duyang Gao, Christopher J. Butch, Yiqing Wang, Hairong Zheng, Zonghai Sheng
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Nanobiotechnology
Online Access:https://doi.org/10.1186/s12951-025-03572-y
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author Shengnan Yuan
Dehong Hu
Duyang Gao
Christopher J. Butch
Yiqing Wang
Hairong Zheng
Zonghai Sheng
author_facet Shengnan Yuan
Dehong Hu
Duyang Gao
Christopher J. Butch
Yiqing Wang
Hairong Zheng
Zonghai Sheng
author_sort Shengnan Yuan
collection DOAJ
description Abstract The blood-brain barrier (BBB) poses a major challenge to the effective delivery of therapeutic agents for the treatment of central nervous system (CNS) disorders. The integration of cell membrane engineering with nanotechnology has recently enabled the development of membrane-engineered nanoparticles (CNPs). These nanocarriers exhibit enhanced BBB penetration and improved CNS targeting. This review systematically summarizes the latest advances in the development and application of CNPs, emphasizing how different cellular sources—such as erythrocytes, platelets, tumor cells, and leukocytes—impact delivery efficiency and therapeutic outcomes. We also examine the molecular mechanisms underlying nanoparticle-BBB interactions and highlight the importance of biosafety evaluations. Moreover, critical barriers to clinical translation, including large-scale manufacturing challenges, batch-to-batch variability, and regulatory complexities, are discussed. Finally, we explore emerging strategies—particularly the integration of artificial intelligence (AI)—that hold potential for overcoming existing clinical gaps, enabling the rational design and optimized development of CNP-based therapeutics for CNS disorders. By integrating mechanistic insights with translational perspectives, this review provides a clear conceptual and technological foundation for the development of next-generation CNS-targeted nanotherapeutics.
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publisher BMC
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spelling doaj-art-7788e58905dd4de3a8ffd381df80aad12025-08-20T04:03:07ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123112210.1186/s12951-025-03572-yRecent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrierShengnan Yuan0Dehong Hu1Duyang Gao2Christopher J. Butch3Yiqing Wang4Hairong Zheng5Zonghai Sheng6Research Center for Advanced Detection Materials and Medical Imaging Devices, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesResearch Center for Advanced Detection Materials and Medical Imaging Devices, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesResearch Center for Advanced Detection Materials and Medical Imaging Devices, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesDepartment of Biomedical Engineering, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing UniversityDepartment of Biomedical Engineering, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing UniversityResearch Center for Advanced Detection Materials and Medical Imaging Devices, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesResearch Center for Advanced Detection Materials and Medical Imaging Devices, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesAbstract The blood-brain barrier (BBB) poses a major challenge to the effective delivery of therapeutic agents for the treatment of central nervous system (CNS) disorders. The integration of cell membrane engineering with nanotechnology has recently enabled the development of membrane-engineered nanoparticles (CNPs). These nanocarriers exhibit enhanced BBB penetration and improved CNS targeting. This review systematically summarizes the latest advances in the development and application of CNPs, emphasizing how different cellular sources—such as erythrocytes, platelets, tumor cells, and leukocytes—impact delivery efficiency and therapeutic outcomes. We also examine the molecular mechanisms underlying nanoparticle-BBB interactions and highlight the importance of biosafety evaluations. Moreover, critical barriers to clinical translation, including large-scale manufacturing challenges, batch-to-batch variability, and regulatory complexities, are discussed. Finally, we explore emerging strategies—particularly the integration of artificial intelligence (AI)—that hold potential for overcoming existing clinical gaps, enabling the rational design and optimized development of CNP-based therapeutics for CNS disorders. By integrating mechanistic insights with translational perspectives, this review provides a clear conceptual and technological foundation for the development of next-generation CNS-targeted nanotherapeutics.https://doi.org/10.1186/s12951-025-03572-y
spellingShingle Shengnan Yuan
Dehong Hu
Duyang Gao
Christopher J. Butch
Yiqing Wang
Hairong Zheng
Zonghai Sheng
Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier
Journal of Nanobiotechnology
title Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier
title_full Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier
title_fullStr Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier
title_full_unstemmed Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier
title_short Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier
title_sort recent advances of engineering cell membranes for nanomedicine delivery across the blood brain barrier
url https://doi.org/10.1186/s12951-025-03572-y
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