Rapid Cellular Internalization of Multifunctional Star Polymers Prepared by Atom Transfer Radical Polymerization

Abstract

Poly(ethylene glycol) (PEG) star polymers containing GRGDS (Gly-Arg-Gly-Asp-Ser) peptide sequences on the star periphery were synthesized by atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA), GRGDS modified poly(ethylene glycol) acrylate (GRGDS-PEG-Acryl), fluorescein o-methacrylate (FMA), and ethylene glycol dimethacrylate (EGDMA) via an "arm-first" method. Star polymers were approximately 20 nm in diameter, as measured by dynamic light scattering and atomic force microscopy. Conjugation of FMA to the stars was confirmed by fluorescence microscopy, and successful attachment of GRGDS segments to the star periphery was confirmed by (1)H NMR spectroscopy. Both fluorescent PEG star polymers with and without peripheral GRGDS peptide segments were cultured with MC3T3-E1.4 cells. These star polymers were biocompatible with ≥ 90% cell viability after 24 h of incubation. Cellular uptake of PEG star polymers in MC3T3-E1.4 cells was observed by confocal microscopy. Rapid uptake of PEG star polymers with GRGDS peptides (∼ 100% of FITC-positive cells in 15 min measured by flow cytometry) was observed, suggesting enhanced delivery potential of these functional star polymers.

ATRP in the design of functional materials for biomedical applications

“…4a). Flow cytometry experiments showed that peptide functionalization increased cellular uptake in vitro [166,175]. FITC-Dx-loaded nanogels were also able to effectively internalize into a spheroidal co-culture of human umbilical vascular endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs), which validated cellular endocytosis into a more complex system (Fig.…”

Emerging Synthetic Strategies for Core Cross‐Linked Star (CCS) Polymers and Applications as Interfacial Stabilizers: Bridging Linear Polymers and Nanoparticles

“…The unique architecture of CCS polymers has enabled their applications in a wide array of areas, including drug delivery, imaging, catalysis, sensing, film formation, and self‐assembly . While the potential of CCS polymers in these applications has been well appreciated, their use as interfacial stabilizers has been much less studied.…”

Brush‐first and Click: Efficient Synthesis of Nanoparticles that Degrade and Release Doxorubicin in Response to Light

“…Great effort has been devoted to the synthesis of nanoparticlebased drug delivery systems for cancer therapy (1)(2)(3). Many basic parameters of ideal systems have been defined (4)(5)(6), and a myriad of materials have been reported (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21); many are nearing clinical use (22)(23)(24)(25)(26)(27). There remains room for improvement, particularly in the realm of efficient drug carrier synthesis.…”