Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

Janina-Miriam Noy; Fan Chen; Martina Stenzel

doi:10.3762/bjoc.17.148

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

Beilstein J Org Chem. 2021 Sep 3:17:2302-2314. doi: 10.3762/bjoc.17.148. eCollection 2021.

Authors

Janina-Miriam Noy¹, Fan Chen¹, Martina Stenzel¹

Affiliation

¹ School of Chemistry, University of New South Wales, Sydney NSW 2052, Australia.

Abstract

Herein, the postfunctionalization of different non-fouling PISA particles, prepared from either poly(oligo ethylene glycol methyl ether methacrylate) (pPEGMA) and the anticancer drug PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsenonous acid) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and PENAO were reported. Both PISA particles were reacted with triphenylphosphonium (TPP) as mitochondria targeting units in order to evaluate the changes in cellular uptake or the toxicity of the conjugated arsenic drug. Attachment of TPP onto the PISA particles however was found not to enhance the mitochondrial accumulation, but it did influence overall the biological activity of pMPC-based particles in 2D and 3D cultured sarcoma SW982 cells. When TPP was conjugated to the pMPC PISA particles more cellular uptake as well as better spheroid penetration were observed, while TPP on PEG-based PISA had only little effect. It was hypothesized that TPP on the micelle surface may not be accessible enough to allow mitochondria targeting, but more structural investigations are required to elucidate this.

Keywords: PISA; micelle; mitochondria; phosphorylcholine; polymerization-induced self-assembly.

Grants and funding

The authors would also like to thank the Australian Government and the Australian Research Council for funding.