Pentafluorophenyl-based single-chain polymer nanoparticles as a versatile platform towards protein mimicry

Abstract

Proteins are biopolymers folded into 3D-structures and are omnipresent in biological systems, where they fulfil a wide array of complex functions. Mimicking the exceptional characteristics of proteins with synthetic analogues...

Cytosolic Delivery of Single-Chain Polymer Nanoparticles

“…PFP-SCNPs were prepared by slow addition of thiol-functionalized co-polymer to a cross-linker solution as reported earlier. 43,50 GPC analysis showed an apparent size reduction of 51% after collapse into SCNPs, indicating successful intramolecular cross-linking (Figure S1). DLS measurements showed the formation of particles with a diameter of 12 nm, with no significant larger-sized clusters present (Figure S2).…”

“…We previously reported that SCNPs with 1-aminoglycerol surface functionalities do not display adverse effects on the viability of human cerebral endothelial cells (hCMEC/D3) . However, cationic charges on the NP surface induced by protonation of tertiary amine groups are known to generate cytotoxic effects. ,, Cytotoxicity of the SCNPs was therefore evaluated on a mouse endothelial cell line (bEND.3) utilizing a resazurin assay.…”

“…This combines the ability for multivalent target–ligand interactions, with the increased cellular uptake seen for rigid particles. , Furthermore, SCNPs with PTR86, a targeting ligand for pancreatic cancer, have been shown to accumulate at the tumor site in a murine model, demonstrating that SCNPs can avoid fast renal clearance . These characteristics have led to SCNPs being investigated in various biomedical applications, such as drug delivery, ,− targeting, , protein mimicry, − imaging, , sensing, and even catalysis. ,, …”

“…These results emphasize the demand of amines with high buffer capacity to enable the cytosolic release. In previous work, pentafluorophenyl-functional (PFP) SCNPs were synthesized via thiol-Michael addition displaying the ability for a variety of highly controlled functionalizations for biomedical applications. , PFP-SCNPs were functionalized with various peptides to develop protein mimics.…”

Green light enabled Staudinger–Bertozzi ligation

“…3 However, the phosphine probes have higher metabolic stability in biological environments, which affords facile and selective conjugation to the targeted biomacromolecules both in vivo and in vitro . 4 Thus, despite the emergence of new bioorthogonal coupling chemistries, 5 including the isonitrile and nitrile oxide cycloadditions, 6,7 inverse electron demand Diels–Alder reactions, 8–10 nucleophilic thiol-addition, 11,12 and pentafluorophenyl-based S N Ar reactions, 13–15 the Staudinger–Bertozzi ligation remains an indispensable tool for bioconjugation. 16 Critically, the ligation can be conducted in the presence of living cells without notable toxicity, enabling the modification and labelling of cell surfaces.…”