Enhanced colloidal stability and protein resistance of layered double hydroxide nanoparticles with phosphonic acid-terminated PEG coating for drug delivery

Zhenbang Cao; Nik Nik M Adnan; Guoying Wang; Aditya Rawal; Bingyang Shi; Ruizhe Liu; Kang Liang; Lingyun Zhao; J Justin Gooding; Cyrille Boyer; Zi Gu

doi:10.1016/j.jcis.2018.03.006

Enhanced colloidal stability and protein resistance of layered double hydroxide nanoparticles with phosphonic acid-terminated PEG coating for drug delivery

J Colloid Interface Sci. 2018 Jul 1:521:242-251. doi: 10.1016/j.jcis.2018.03.006. Epub 2018 Mar 3.

Authors

Zhenbang Cao¹, Nik Nik M Adnan², Guoying Wang³, Aditya Rawal⁴, Bingyang Shi³, Ruizhe Liu², Kang Liang¹, Lingyun Zhao⁵, J Justin Gooding⁶, Cyrille Boyer⁷, Zi Gu⁸

Affiliations

¹ School of Chemical Engineering, University of New South Wales, Sydney, Australia; Australian Centre for NanoMedicine (ACN), University of New South Wales, Sydney, Australia.
² School of Chemical Engineering, University of New South Wales, Sydney, Australia.
³ Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Macquarie University, Sydney, Australia.
⁴ NMR Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia.
⁵ State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, China.
⁶ Australian Centre for NanoMedicine (ACN), University of New South Wales, Sydney, Australia; School of Chemistry and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney, Australia.
⁷ School of Chemical Engineering, University of New South Wales, Sydney, Australia; Australian Centre for NanoMedicine (ACN), University of New South Wales, Sydney, Australia. Electronic address: cboyer@unsw.edu.au.
⁸ School of Chemical Engineering, University of New South Wales, Sydney, Australia; Australian Centre for NanoMedicine (ACN), University of New South Wales, Sydney, Australia. Electronic address: zi.gu1@unsw.edu.au.

PMID: 29574343
DOI: 10.1016/j.jcis.2018.03.006

Abstract

Conjugating nanoparticles with polyethylene glycol (PEG) is a useful strategy to improve the colloidal and biological stability of nanoparticles. However, studies on PEGylation of two-dimensional layered double hydroxide (LDH) nanoparticles are very limited. The present work reported two functionalization approaches to synthesize PEG-conjugated LDH nanoparticles by introducing phosphonic acid terminated PEG before and after LDH aging. The successful PEGylation was confirmed and suggested to be via electrostatic interaction and a ligand exchange process. Different functionalization approaches resulted in different binding types of PEG on/in LDH nanoparticles. The PEG coating maintained the dispersity of LDH nanoparticles in water and saline with the feeding mass ratio of 1:1. Further colloidal stability tests of PEGylated LDHs revealed that the PEGylated LDH dispersity was affected by the feeding mass ratio of PEG/LDH, the molar weight of PEG and anions intercalated in the LDHs. In a test to determine the extent of non-specific protein adsorption, the PEGylation was effective at resisting non-specific bovine serum albumin adsorption on LDH nanoparticles with both functionalization methods investigated. Moreover, PEGylated LDH nanoparticles had no effect on cell viability up to 500 µg/mL, and demonstrated enhanced cellular uptake in a SK-MEL-28 cell culture. The results in this work indicate that conjugating phosphonic acid-terminated PEG on LDH nanoparticles is a promising strategy to improve the colloidal and biological stability of LDHs for biomedical applications.

Keywords: Layered double hydroxide; Nanoparticle; Non-specific protein adsorption; PEGylation; Stability.

MeSH terms

Adsorption
Cell Line, Tumor
Cell Survival / drug effects
Colloids
Drug Carriers / chemistry*
Drug Carriers / toxicity
Excipients / chemistry
Fluorescein-5-isothiocyanate / chemistry
Fluorescent Dyes / chemistry
Humans
Hydroxides / chemistry*
Nanoparticles / chemistry*
Nanoparticles / toxicity
Particle Size
Phosphorous Acids / chemistry*
Polyethylene Glycols / chemistry*
Serum Albumin, Bovine / chemistry
Solubility
Surface Properties
Water

Substances

Colloids
Drug Carriers
Excipients
Fluorescent Dyes
Hydroxides
Phosphorous Acids
Water
Serum Albumin, Bovine
Polyethylene Glycols
Fluorescein-5-isothiocyanate