Poly(ε-caprolactone)-block-polysarcosine by Ring-Opening Polymerization of Sarcosine N-Thiocarboxyanhydride: Synthesis and Thermoresponsive Self-Assembly

Abstract

Biocompatible amphiphilic block copolymers composed of polysarcosine (PSar) and poly(ε-caprolactone) (PCL) were synthesized using ring-opening polymerization of sarcosine N-thiocarboxyanhydride initiated by oxyamine-ended PCL and characterized by NMR, SEC, and DSC. Self-assembling of two triblock copolymers PSar8-b-PCL28-b-PSar8 (CS7) and PSar16-b-PCL40-b-PSar16 (CS10) in dilute solution was studied in detail toward polymersome formation using thin-film hydration and nanoprecipitation techniques. A few giant vesicles were obtained by thin-film hydration from both copolymers and visualized by confocal laser scanning microscope. Unilamellar sheets and nanofibers (with 8-10 nm thickness or diameter) were obtained by nanoprecipitation at room temperature and observed by Cryo-TEM. These lamellae and fibrous structures were transformed into worm-like cylinders and spheres (D∼30-100 nm) after heating to 65 °C (>Tm,PCL). Heating CS10 suspensions to 90 °C led eventually to multilamellar polymersomes (D∼100-500 nm). Mechanism II, where micelles expand to vesicles through water diffusion and hydrophilic core forming, was proposed for polymersome formation. A cell viability test confirmed the self-assemblies were not cytotoxic.

Poly(sarcosine)-Based Nano-Objects with Multi-Protease Resistance by Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA)

“…10 However, PEG is known to be a non-bio-based and non-biodegradable polymer with limited functionality, while studies have also shown oxidative activity of PEG in physiological cellular environments, immune response of patients and accelerated blood clearance phenomena caused by anti-PEG antibodies. [11][12][13][14] Consequently, in recent years there is a growing demand for finding alternatives to overcome these limitations of PEG. 15 A broad variety of hydrophilic polymers including poly(glycerols), 16 poly(oxazolines), 17 poly(peptides) 18 and poly(peptoids) 19 with comparable physicochemical properties to PEG have been currently explored and proposed as promising alternatives.…”

“…23 Over the last years, studies on the synthesis and self-assembly behavior of PSar-based block copolymers for the development of nanostructures of biotechnological interest have been presented, although they involve the use of conventional self-assembly procedures in dilute aqueous solutions. 13,23,[27][28][29][30][31][32] Recently, polymerization-induced self-assembly (PISA) has been established as an efficient methodology for facile one-pot fabrication of polymeric nano-objects with predictable morphologies at high solids concentrations (10-50% w/w). [33][34][35][36] Existing limitations of traditional self-assembly strategies (i.e.…”

Aqueous Self‐Assembly of Y‐Shaped Amphiphilic Block Copolymers into Giant Vesicles

“…GUVs, which under consideration here were polymer based, can be achieved with several methods, including electroformation in sucrose or buffer solutions, swelling in solution, emulsion centrifugation, drying–rehydration, microfluidics, and thin‐film hydration based on using conventional structure amphiphilic block molecules . For example, Discher et al have previously found that the linear amphiphilic diblock copolymers, polyethyleneoxide–polyethylethylene (EO 40 –EE 37 ), can be used to prepare GUVs by electroformation in aqueous solution.…”

Amphiphilic block copolymer poly(lactic acid)‐block‐(glycidylazide polymer)‐block‐polystyrene: synthesis and self‐assembly

“…When dissolved in appropriate solvents, amphiphilic block copolymers show characteristic behavior and form micelles of spherical, vesicular, worm‐like and tubular structures through self‐assembly . Existing research has mainly focused on using water, instead of organic solvents, to initiate the self‐assembly of amphiphilic block copolymers . Compared with diblock copolymers, triblock copolymers possess additional morphological features and can serve as templates for the synthesis of nanoporous materials through selective removal of etchable components.…”