4.8 Article

Modular design of Bi-specific nanoplatform engaged in malignant lymphoma immunotherapy

Journal

NANOSCALE
Volume 12, Issue 35, Pages 18418-18428

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d0nr04450d

Keywords

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Funding

  1. National Key Research and Development Program of China [2017YFA0205502]
  2. National Natural Science Foundation of China [81571806, 81671820]
  3. Science and Technology Support Project of Jiangsu Province [BE2017763]
  4. Medical Research Project of Jiangsu Province Health Committee [K2019020]
  5. Basic Research Program of Jiangsu Province (Natural Science Foundation) [BK 20181086]
  6. Fundamental Research Funds for the Central Universities

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Nanocarrier systems play an important role in cancer immunotherapy. In this article, biotinylated CD20 and CD3 antibodies were conjugated onto the surface of streptavidin modified ultra-small Fe(3)O(4)nanoparticlesviaspecific binding between streptavidin and biotin to construct a bi-specific nanoplatform (BSNP). The synthesized BSNP with 30 nm hydrodynamic size provides a better magnetic resonance imaging ability than the clinical Gd-chelated contrast agents (r(1)value is 5.27 mM(-1)s(-1)and 4.52 mM(-1)s(-1)for BSNP and Magnevist, respectively). This nanoplatform can target CD20-positive Raji cells and enhance the T cell mediated cell killing effectin vitro. Further, it can also inhibit tumor growth and prolong the survival time of non-Hodgkin's lymphoma (NHL) xenograft modelin vivo. The probable mechanism is that while BSNP can directly induce the apoptosis of Raji cellviaaggregation of CD20, T cells are recruited around tumor cells by the BSNP leading to T cell-mediated tumor cell lysis. In addition, the enhanced dual-modal MRI-fluorescence images can be acquired. In summary, the modular designed BSNP provides an efficient immune-related cancer theranostic strategy, which is of great potential as a simple and universal nanoplatform by combining different antibodies to enhance the cancer theranostic efficacy.

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