Cationic poly(amino acid) surface functionalized manganese nanoparticles for nitric oxide-based immunotherapy and magnetic resonance imaging

Jong Woo Lim, Hye Young Son, Yong Min Huh, Seungjoo Haam

Research output: Contribution to journalArticlepeer-review

Abstract

The low therapeutic efficacy of conventional cancer chemotherapy has been associated with an immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs), which display an M2-like phenotype, are abundant in many tumors and facilitate tumor growth and resistance to therapy. Here, we show that poly(l-arginine) (PLR), a cationic poly(amino acid) can induce the polarization of macrophages into the tumor-suppressive M1 phenotype, in vitro. Further, we demonstrate that hyaluronic acid (HA) and PLR-coated manganese dioxide (MnO2) nanoparticles (hpMNPs) display efficient anti-cancer effects by upregulating nitric oxide (NO) production. Surface modification with biocompatible HA reduced the cytotoxicity of the cationic PLR. Additionally, manganese ions released from these nanoparticles by the high concentrations of glutathione (GSH) in the TME increased iNOS expression level in macrophages and enhanced the performance of T1 weighted magnetic resonance imaging. Particularly, our results illustrate the therapeutic effects, such as growth inhibition and apoptosis of tumor cells, of hpMNP treated macrophages. Therefore, the newly designed multifunctional PLR-assisted MNPs may facilitate the polarization of M2 macrophages into the M1 phenotype, which can mediate NO-dependent anticancer immunotherapy.

Original languageEnglish
Pages (from-to)5402-5409
Number of pages8
JournalJournal of Materials Chemistry B
Volume10
Issue number28
DOIs
Publication statusPublished - 2022 Jun 29

Bibliographical note

Funding Information:
This research was supported by National R&D Programs of the National Research Foundation (NRF) funded by the Ministry of Science & ICT(NRF-2018M3A9E2022819, NRF-2017M3A9G508332, NRF-2021M3E5E3080565)

Publisher Copyright:
© 2022 The Royal Society of Chemistry.

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

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