A facile approach to functionalizing cell membrane-coated nanoparticles with neurotoxin-derived peptide for brain-targeted drug delivery
Abstract
The blood brain barrier separates the circulating blood from the extracellular fluid in the central nervous system and thus presents an essential obstacle to brain transport of therapeutics. Herein, we report on an effective brain-targeted drug delivery system that combines a robust red blood cell membrane-coated nanoparticle (RBCNP) with a unique neurotoxin-derived targeting moiety. The RBCNPs retain the complex biological functions of natural cell membranes while exhibiting physicochemical properties that are suitable for effective drug delivery. CDX peptide is derived from candoxin and shows high binding affinity with nicotinic acetylcholine receptors (nAChRs) expressed on the surface of brain endothelial cells. Through a facile yet robust approach, we successfully incorporate D CDX peptides onto the surface of RBCNPs without compromising the peptide's brain targeting ability. The resulting D CDX-RBCNPs show promising brain targeting efficiency both in vitro and in vivo. Using a glioma mouse model, we demonstrate that doxorubicin-loaded D CDX-RBCNPs have superior therapeutic efficacy and markedly reduced toxicity as compared to the nontargeted drug formulations. While RBCNPs are used as a model system to evaluate the surface modification approach, the reported method can be readily generalized to various types of cell membrane-derived nanocarriers for broad medical applications.
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Red blood cell membrane-peptide-coated systems can traverse BBB, display brain targeting, release DOX, and prolong survival of mice.
“red blood cell membrane-peptide-coated systems not only had the capability to traverse the BBB, displaying exceptional brain targeting effect, but also could release DOX and prolong the survival of mice.”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [197]
Red cell membrane coating improves circulation time and locates systems close to tumor vessels.
“they verified the red cell membrane coating could improve the circulation time of the systems and locate them close to tumor vessels.”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [197]
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- Authors
- Chai, Z., Hu, X., Wei, X., Zhan, C., Lu, L., Jiang, K., Su, B., Ruan, H., Ran, D., Fang, R. H., Zhang, L., & Lu, W.
- Affiliations
- Fudan University (CN)
- Shanghai Medical College of Fudan University (CN)
- University of California San Diego (US)
- Corresponding author
- Zhang, Liangfang
- Lu, Weiyue
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 264
- Pages
- 102-111
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2746191133
- Cited by
- 253
- References
- 44
- Citations by year
- 2026: 13 · 2025: 32 · 2024: 36 · 2023: 40 · 2022: 29 · 2021: 26 · 2020: 36 · 2019: 23 · 2018: 18
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Basic Research Program of China (2013CB932500)
- National Natural Science Foundation of China (81690263, 81473149)
- International Science & Technology Cooperation Foundation of Shanghai (16430723800)
- National Institutes of Health (R01CA200574)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- brain drug delivery, blood-brain barrier, nicotinic acetylcholine receptors, brain endothelial cells, doxorubicin, glioma, surface functionalization
- MeSH terms
- Animals, Antineoplastic Agents, Biotin, Brain, Brain Neoplasms, Cells, Cultured, Doxorubicin, Erythrocyte Membrane, Glioma, Gold, Humans, Male, Mice, Inbred ICR, Mice, Nude, Peptides, Polyethylene Glycols, Receptors, Nicotinic, Snake Venoms, Drug Delivery Systems, Rats, Wistar, Streptavidin, Endothelial Cells, Cell Line, Tumor, Metal Nanoparticles, Drug Liberation
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