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Cited by 108Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsMonoclonal and Polyclonal Antibodies Research

Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice

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Wen, Jing, Wu, Di, Qin, Meng, Liu, Chaoyong, Wang, Lan, Xu, Duo, Vinters, Harry V., Liu, Yang +10 more·2019·Nature Biomedical Engineering
DOI 10.1038/s41551-019-0434-zPMC PMC6736720
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Abstract

Approximately 15-40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13-the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma-a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow-liver-thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases.

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  • Complicated modifications are always needed to ensure that nanoparticles produced are blood-brain barrier-permeable.

    “Crossing the BBB with various nanoparticles, such as liposomes, cationic polymers, inorganic nanoparticles, and nanocapsules, has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable (15, 18, 19).”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [19]

    The Abstract (page unavailable) describes difficulties with existing CNS delivery vehicles and says substantial improvements are needed, while Results and discussion, “Nanocapsules facilitate CNS penetration” (page unavailable), describes an engineered nanocapsule designed for brain delivery. Neither passage establishes that complicated modifications are always necessary for every nanoparticle to cross the BBB; that universal requirement overstates the paper. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Crossing the BBB with various nanoparticles has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable.

    “Among a number of approaches, crossing the BBB with various nanoparticles has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable (15, 18, 19).”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [19]

    The opening background passage (labeled Abstract in our copy; page unavailable) says several carrier approaches, including nanoparticles, have shown promise for CNS delivery but need improvement. It describes ligand-conjugated polymer nanoparticles and their limitations, but does not say complicated modifications are always necessary to make nanoparticles BBB-permeable. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Crossing the blood-brain barrier with nanoparticles such as liposomes, cationic polymers, inorganic nanoparticles, and nanocapsules has shown promise in delivery of various cargos into the CNS.

    “Crossing the BBB with various nanoparticles, such as liposomes, cationic polymers, inorganic nanoparticles, and nanocapsules, has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable (15, 18, 19).”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [19]

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Cited by

Sorted by citations

Authors
Wen, J., Wu, D., Qin, M., Liu, C., Wang, L., Xu, D., Vinters, H. V., Liu, Y., Kranz, E., Guan, X., Sun, G., Sun, X., Lee, Y., Martinez-Maza, O., Widney, D., Lu, Y., Chen, I. S. Y., & Kamata, M.
Affiliations
  • University of California, Los Angeles (US)
  • Nankai University (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
  • Lu, Yunfeng
  • Chen, Irvin S. Y.
  • Kamata, Masakazu
ORCID
Venue
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Published
2019-08-05
Volume
3
Issue
9
Pages
706-716
ISSN
2157-846X (ISSN-L)
DOI
10.1038/s41551-019-0434-z
PMC
PMC6736720
OpenAlex
W2966474758
Cited by
108
References
3
Citations by year
2026: 8 · 2025: 18 · 2024: 11 · 2023: 18 · 2022: 17 · 2021: 21 · 2020: 13 · 2019: 2
FWCI
3.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Biomedical Engineering (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Cancer Institute (R01CA232015, R01CA253215, P50CA211015, P30CA016042)
  • National Institute of Allergy and Infectious Diseases (U19AI117941, R21AI114433, P30AI028697, R01AI110200)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords
rituximab, central nervous system metastasis, sustained drug release, zwitterionic polymers, polymer encapsulation, CXCL13, CXCR5, chemokine receptor targeting, non-Hodgkin lymphoma, B-cell lymphoma, antibody drug delivery, humanized mice, tumor targeting
MeSH terms
Rituximab, Animals, Antibodies, Monoclonal, Brain, Central Nervous System, Disease Models, Animal, Lymphatic Metastasis, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Drug Delivery Systems, Xenograft Model Antitumor Assays, Mice, Nanocapsules, Receptors, CXCR5, Chemokine CXCL13, Molecular Targeted Therapy

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