Palladium Nanoplate-Based IL-6 Receptor Antagonists Ameliorate Cancer-Related Anemia and Simultaneously Inhibit Cancer Progression

Nano Lett. 2022 Jan 26;22(2):751-760. doi: 10.1021/acs.nanolett.1c04260. Epub 2022 Jan 14.

Abstract

In recent years, targeted therapies and immunotherapeutics, along with conventional chemo- and radiotherapy, have greatly improved cancer treatments. Unfortunately, in cancer patients, anemia, either as a complication of cancer progression or as the result of cancer treatment, undermines the expected therapeutic efficacy. Here, we developed a smart nanosystem based on the palladium nanoplates (PdPLs) to deliver tocilizumab (TCZ, a widely used IL-6R antibody) to the liver for specific blockade of IL-6/IL-6R signaling to correct anemia. With chemical modifications, this nanosystem delivered a large mass of TCZ and enhanced liver delivery, inducing a marked suppression of hepcidin expression as a result of diminished IL-6 signaling. Through this mechanism, significant suppression of tumor progression was realized (at least in part) because of the corrected anemia after treatment.

Keywords: IL-6 receptor antagonist; anemia of inflammation; cancer-related anemia; iron; palladium nanoplates; tocilizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia* / drug therapy
  • Anemia* / etiology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Palladium / pharmacology
  • Palladium / therapeutic use
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / metabolism

Substances

  • Interleukin-6
  • Receptors, Interleukin-6
  • Palladium