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

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.

RAFT-mediated polymerization-induced self-assembly (RAFT-PISA): current status and future directions

“…39 In more recent reports by Stenzel et al , the anticancer drug 4-( N -( S -penicillaminylacetyl)amino)phenylarsenonous acid (PENAO) methacrylate prodrug was copolymerized with OEGMA or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) to synthesize macro-CTAs for PISA. 42,43 The prepared nanoparticles with drug covalently linked to shell block were compared in terms of cytotoxicities, cellular uptakes, spheroid penetration, and cell localization profiles.…”

“…20 Up to now, many morphologies have been realized via PISA, including spheres, rods, worms, vesicles, framboidal vesicles, 21,22 multilamellar vesicles, 23 lamellae, 24 spongosomes, [25][26][27][28][29][30][31] hexosomes, [25][26][27]32 cubosomes, 25,26,32 Janus particles, 33,34 colloidal molecules, 33,34 and many others. The synthesized particles have a broad range of applications in the areas of biomedical, [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] coating, 54,55 catalysis [56][57][58][59][60] and Pickering emulsions 22,[61]<...…”

(Bio)degradable and Biocompatible Nano-Objects from Polymerization-Induced and Crystallization-Driven Self-Assembly

“… It resulted in polymer prodrug micelles of 30–40 nm in diameter that exhibited tunable cytotoxicity as a function of the PMPC chain length: reducing the PMPC chain length from 37 to 13 repeating units led to a 5-fold increase in cytotoxicity. These nanoparticles can be postfunctionalized on their surface by triphenylphosphonium (TPP) as a mitochondria targeting agent, resulting in an improvement of tumor penetration and cytotoxicity . Interestingly, when OEGMA was used instead of MPC, the surface functionalization of resulting nanoparticles by TPP had little effect on their biological performances, likely because of a higher steric hindrance around TPP moieties caused by OEGMA side chains compared to MPC moieties.…”

“…These nanoparticles can be postfunctionalized on their surface by triphenylphosphonium (TPP) as a mitochondria targeting agent, resulting in an improvement of tumor penetration and cytotoxicity. 120 Interestingly, when OEGMA was used instead of MPC, the surface functionalization of resulting nanoparticles by TPP had little effect on their biological performances, likely because of a higher steric hindrance around TPP moieties caused by OEGMA side chains compared to MPC moieties.…”

Triphenylphosphonium-Driven Targeting of Pyrimorph Fragment Derivatives Greatly Improved Its Action on Phytopathogen Mitochondria

“…On the other hand, the mitochondrial membrane potential generally ranges between −150 and −180 mV in vivo, which is much higher than that of other cellular organelles. , These two characteristics enable TPP to be easily accumulated in mitochondria and thus be widely used in mitochondria-targeted drug design, − and the conjugation of the lipophilicphosphonium cation to pharmaceutic molecules may change its physical properties and affect its penetration through cell membranes. Cationic amphiphilic compounds have biological activities such as antibacterial, antifungal, antiprotozoal, antitumor, and immunomodulatory effects. − In our previous studies, we have shown the potential of this strategy in the novel fungicide development targeting respiratory chain complexes. , …”