ArticleProceedings of the National Academy of Sciences of the United States of America2015
Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
120 citing papers in PubMed, 269 citations in OpenAlex.
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- PLGA Nanoparticle-based Anti-TLR2 scFv Gene Delivery for the Treatment of Alzheimer's Disease.Experimental neurobiology · 2026Article
- Dichotomous role of CD47-SIRPActa pharmaceutica Sinica. B · 2026Article
- Peptide-functionalized nanoparticles for brain-targeted therapeutics.Drug delivery and translational research · 2026Review
- Crossing the Blood-Brain Barrier with Molecularly Imprinted Polymeric Nanocarriers: An Emerging Frontier in Brain Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Diversity and function of tumor-associated macrophages in brain metastases: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Nanoparticle-Mediated Transcytosis in Tumor Drug Delivery: Mechanisms, Categories, and Novel Applications.Current drug delivery · 2026Review
- Recent advances in potential drug nanocarriers for CNS disorders: a review.Biomedical engineering online · 2025Review
- Mapping research hotspots and trends in hepatocellular carcinoma nanomedicine: a bibliometric analysis.Discover oncology · 2025Article
- Responsive mesoporous silica nanocarriers in glioma therapy: A step forward in overcoming biological barriers.World journal of clinical oncology · 2025Review
- Visualising sub-second dynamics of nanoparticle extravasationbioRxiv : the preprint server for biology · 2025Article
- Developments in nanotechnology approaches for the treatment of solid tumors.Experimental hematology & oncology · 2025Review
- Engineered brain-targeting exosome for reprogramming immunosuppressive microenvironment of glioblastoma.Exploration (Beijing, China) · 2025Article
- Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.Translational neurodegeneration · 2025Review
- Human Embryonic Kidney HEK293 Cells as a Model to Study SMVT-Independent Transport of Biotin and Biotin-Furnished Nanoparticles in Targeted Therapy.International journal of molecular sciences · 2025Article
- Functional Monomers Equipped Microgel System for Managing Parkinson's Disease by Intervening Chemokine Axis-mediated Nerve Cell Communications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inorganic Nanoparticles-based Drug Delivery Systems for Neurodegenerative Diseases Therapy.Current pharmaceutical design · 2025Review
- Nanoparticles in CNS Therapeutics: Pioneering Drug Delivery Advancements.Current pharmaceutical design · 2025Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.