A Bioactive Disintegrable Polymer Nanoparticle for Synergistic Vascular Anticalcification

Hossein Adelnia; Shehzahdi Shebbrin Moonshi; Yuao Wu; Andrew C Bulmer; Ryan Mckinnon; Jarred William Fastier-Wooller; Idriss Blakey; Hang Thu Ta

doi:10.1021/acsnano.3c03041

A Bioactive Disintegrable Polymer Nanoparticle for Synergistic Vascular Anticalcification

ACS Nano. 2023 Oct 10;17(19):18775-18791. doi: 10.1021/acsnano.3c03041. Epub 2023 Aug 31.

Authors

Hossein Adelnia^{1

2}, Shehzahdi Shebbrin Moonshi¹, Yuao Wu¹, Andrew C Bulmer³, Ryan Mckinnon³, Jarred William Fastier-Wooller⁴, Idriss Blakey², Hang Thu Ta^{1

2

5}

Affiliations

¹ Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, Queensland 4111, Australia.
² Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, Queensland 4072, Australia.
³ School of Pharmacy and Medical Sciences, Griffith University, Southport, Queensland 4222, Australia.
⁴ Department Precision Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
⁵ Bioscience Discipline, School of Environment and Science, Griffith University, Nathan, Queensland 4111, Australia.

PMID: 37650798
DOI: 10.1021/acsnano.3c03041

Abstract

Although poly(aspartic acid) (PASP), a strong calcium chelating agent, may be potentially effective in inhibition of vascular calcification, its direct administration may lead to side effects. In this study, we employed polysuccinimide, a precursor of PASP, to prepare targeted polysuccinimide-based nanoparticles (PSI NPs) that not only acted as a prodrug but also functioned as a carrier of additional therapeutics to provide powerful synergistic vascular anticalcification effect. This paper shows that chemically modified PSI-NPs can serve as effective nanocarriers for loading of hydrophobic drugs, in addition to anticalcification and antireactive oxygen species (anti-ROS) activities. Curcumin (Cur), with high loading efficiency, was encapsulated into the NPs. The NPs were stable for 16 h in physiological conditions and then slowly dissolved/hydrolyzed to release the therapeutic PASP and the encapsulated drug. The drug release profile was found to be in good agreement with the NP dissolution profile such that complete release occurred after 48 h at physiological conditions. However, under acidic conditions, the NPs were stable, and Cur cumulative release reached only 30% after 1 week. Though highly effective in the prevention of calcium deposition, PSI NPs could not prevent the osteogenic trans-differentiation of vascular smooth muscle cells (VSMCs). The presence of Cur addressed this problem. It not only further reduced ROS level in macrophages but also prevented osteogenic differentiation of VSMCs in vitro. The NPs were examined in vivo in a rat model of vascular calcification induced by kidney failure through an adenine diet. The inclusion of Cur and PSI NPs combined the therapeutic effects of both. Cur-loaded NPs significantly reduced calcium deposition in the aorta without adversely affecting bone integrity or noticeable side effects/toxicity as examined by organ histological and serum biochemistry analyses.

Keywords: anticalcification; antioxidant; chronic kidney disease; curcumin; polysuccinimide; vascular calcification.