Poly(sarcosine)
(PSar) is a non-ionic hydrophilic polypeptoid with
numerous biologically relevant properties, making it an appealing
candidate for the development of amphiphilic block copolymer nanostructures.
In this work, the fabrication of poly(sarcosine)-based diblock copolymer
nano-objects with various morphologies via aqueous reversible addition–fragmentation
chain-transfer (RAFT)-mediated photoinitiated polymerization-induced
self-assembly (photo-PISA) is reported. Poly(sarcosine) was first
synthesized via ring-opening polymerization (ROP) of sarcosine N-carboxyanhydride, using high-vacuum techniques. A small
molecule chain transfer agent (CTA) was then coupled to the active
ω-amino chain end of the telechelic polymer for the synthesis
of a poly(sarcosine)-based macro-CTA. Controlled chain-extensions
of a commercially available water-miscible methacrylate monomer (2-hydroxypropyl
methacrylate) were achieved via photo-PISA under mild reaction conditions,
using PSar macro-CTA. Upon varying the degree of polymerization and
concentration of the core-forming monomer, morphologies evolving from
spherical micelles to worm-like micelles and vesicles were accessed,
as determined by dynamic light scattering and transmission electron
microscopy, resulting in the construction of a detailed phase diagram.
The resistance of both colloidally stable empty vesicles and enzyme-loaded
nanoreactors against degradation by a series of proteases was finally
assessed. Overall, our findings underline the potential of poly(sarcosine)
as an alternative corona-forming polymer to poly(ethylene glycol)-based
analogues of PISA assemblies for use in various pharmaceutical and
biomedical applications