Abstract

Single-chain polymeric nanoparticles (SCPNs) have great potential as functional nanocarriers for drug delivery and bioimaging, but synthetic challenges in terms of final yield and purification procedures limit their use. A new concept to modify and improve the synthetic procedures used to generate water-soluble SCPNs through amphiphilic interactions has been successfully exploited. We developed a new ultrahigh molecular weight amphiphilic polymer containing a hydrophobic poly(epichlorohydrin) backbone and hydrophilic poly(ethylene glycol) side chains. The polymer spontaneously self-assembles into SCPNs in aqueous solution and does not require subsequent purification. The resulting SCPNs possess a number of distinct physical properties, including a uniform hydrodynamic nanoparticle diameter of 10–15 nm, extremely low viscosity and a desirable spherical-like morphology. Concentration-dependent studies demonstrated that stable SCPNs were formed at high concentrations up to 10 mg/mL in aqueous solution, with no significant increase in solution viscosity. Importantly, the SCPNs exhibited high structural stability in media containing serum or phosphate-buffered saline and showed almost no change in hydrodynamic diameter. The combination of these characteristics within a water-soluble SCPN is highly desirable and could potentially be applied in a wide range of biomedical fields. Thus, these findings provide a path towards a new, innovative route for the development of water-soluble SCPNs.

Highlights

  • Inspiration from nature has been the principal driving force behind the emergence of new functional polymers with unique and desirable physical characteristics that hold great potential for applications in various fields [1,2]

  • Protein folding mediated by noncovalent interactions [4,5] and hierarchical self-assembly [6] have inspired polymer chemists to synthesize single-chain polymeric nanoparticles (SCPNs) via controlled intramolecular chain folding/collapse of individual polymer chains using physical or chemical crosslinking methods [7,8,9,10,11,12]

  • We boldly conjectured that the introduction of hydrophilic polyethylene glycol (PEG) chains into a high-molecular weight hydrophobic polymer backbone may significantly affect the polymer self-assembly process and effectively induce folding/collapse of the polymers into SCPNs in aqueous environments

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Summary

Introduction

Inspiration from nature has been the principal driving force behind the emergence of new functional polymers with unique and desirable physical characteristics that hold great potential for applications in various fields [1,2]. This finding inspired us to further explore a simple and highly efficient route for the synthesis of water-soluble SCPNs. we boldly conjectured that the introduction of hydrophilic PEG chains into a high-molecular weight hydrophobic polymer backbone may significantly affect the polymer self-assembly process and effectively induce folding/collapse of the polymers into SCPNs in aqueous environments.

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