Spontaneous Self-Assembly of Single-Chain Amphiphilic Polymeric Nanoparticles in Water

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.

Water-Soluble Single-Chain Polymeric Nanoparticles for Highly Selective Cancer Chemotherapy

“…Surprisingly, GPC (Figure S2b) indicated that F-PECH-PEG and PECH-PEG have similar flow curves and hydrodynamic behavior in water, demonstrating that the F-PECH-PEG polymer possesses an important characteristic for SCPNs: F-PECH-PEG had a longer retention time than PECH-PEG, lacking the hydrophilic PEG-rich segments. 45 However, F-PECH-PEG had significantly higher d H in water than the PECH-PEG polymer; we speculate that this phenomenon may be related to alterations in the surface charge of F-PECH-PEG induced by incorporation of folic acid, which promotes formation of aggregates of the SCPNs. These observations also strongly suggest that the presence of small amounts of folic acid (as pendant side chains) in the structure of F-PECH-PEG did not appreciably affect its self-assembly ability, that is, F-PECH-PEG can spontaneously assemble into isolated SCPNs in water.…”

“…Ultrahigh molecular-weight water-soluble PECH-PEGs containing pendant PEG chains (molecular-weight 4000 g/mol) and the hydrophobic PECH backbone were prepared using our previously described methods. 45 A SCPN derivative (analogue), folic acid-functionalized F-PECH-PEG, was obtained by cycloaddition of azide-grafted PECH 46 with alkynemodified folic acid 47 (4000 g/mol). The recovery yield for F-PECH-PEG was 60%.…”

“…Synthesis of Folic Acid-Functionalized PECH-PEG. PECH-PEG was prepared using a previously established route; 45 folic acidfunctionalized PECH-PEG (F-PECH-PEG) was synthesized using a similar procedure. Briefly, alkyne-modified folic acid (15 mg, 32.3 μmol), 47 PECH-azide (M W > 700,000 g/mol, degree of polymerization = ca.…”

Stimuli-Free Transcuticular Delivery of Zn Microelement Using Biopolymeric Nanovehicles: Experimental, Theoretical, and In Planta Studies

“…It is important to note that spatial structure significantly influences polymer’s retention time. Because the original CMC has no assembling abilities and CMC-8 is a self-assembled aggregate, the received M n values illustrate a difference between the two polymers but cannot be taken for precise evaluation of molecular weight …”

“…Because the original CMC has no assembling abilities and CMC-8 is a self-assembled aggregate, the received M n values illustrate a difference between the two polymers but cannot be taken for precise evaluation of molecular weight. 43 Computational Modeling Study. Three-dimensional structural modeling, continuum electrostatics calculations, and analysis of polymer chain conformational dynamics were performed to get insight into the self-assembly mechanism of CMC-8 and to understand how the introduction of hydrophobic substituents has led to the enhancement in affinity to highly hydrophilic ionic zinc.…”