Cationic poly(amino acid) surface functionalized manganese nanoparticles for nitric oxide-based immunotherapy and magnetic resonance imaging. Issue 28 (1st July 2022)

• Record Type: Journal Article
• Authors: Lim, Jong-Woo; Son, Hye Young; Huh, Yong-Min; Haam, Seungjoo
• Is Part Of: Journal of materials chemistry. Volume 10:Issue 28(2022)
• Page Start: 5402
• Page End: 5409
• Publication Date: 2022-07-01
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/d2tb00794k
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : Poly(l -arginine) and hyaluronic acid modified MnO2 nanoparticles (hpMNPs) reprogrammed M2 macrophages to M1 secreting high level of pro-inflammatory cytokines and nitric oxide, leading to apoptosis of tumor cells. 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 T 1 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.