As a relatively new class of materials, single-chain polymer nanoparticles (SCNPs) just entered the field of (biomedical) applications, with recent advances in polymer science enabling the formation of bio-inspired nanosized architectures. Exclusive intramolecular collapse of individual polymer chains results in individual nanoparticles. With sizes an order of magnitude smaller than conventional polymer nanoparticles, SCNPs are in the size regime of many proteins and viruses (1-20 nm). Multifaceted syntheses and design strategies give access to a wide set of highly modular SCNP materials. This review describes how SCNPs have been rendered water-soluble and highlights ongoing research efforts towards biocompatible SCNPs with tunable properties for controlled drug delivery, targeted imaging and protein mimicry.
Single-chain
polymer nanoparticles (SCNPs) are protein-inspired
materials based on intramolecularly cross-linked polymer chains. We
report here the development of SCNPs as uniquely sized nanocarriers
that are capable of drug encapsulation independent of the polarity
of the employed medium. Synthetic routes are presented for SCNP preparation
in both organic and aqueous environments. Importantly, the SCNPs in
organic media were successfully rendered water soluble, resulting
in two complementary pathways toward water-soluble SCNPs with comparable
resultant physicochemical characteristics. The solvatochromic dye
Nile red was successfully encapsulated inside the SCNPs following
both pathways, enabling probing of the SCNP interior. Moreover, the
antibiotic rifampicin was encapsulated in organic medium, the loaded
nanocarriers were rendered water soluble, and a controlled release
of rifampicin was evidenced. The absence of discernible cytotoxic
effects and promising cellular uptake behavior bode well for the application
of SCNPs in controlled therapeutics delivery.
Naturally occurring glycoconjugates
possess carbohydrate moieties
that fulfill essential roles in many biological functions. Through
conjugation of carbohydrates to therapeutics or imaging agents, naturally
occurring glycoconjugates are mimicked and efficient targeting or
increased cellular uptake of glycoconjugated macromolecules is achieved.
In this work, linear and cyclic glucose moieties were functionalized
with methacrylates via enzymatic synthesis and used as building blocks
for intramolecular cross-linked single-chain glycopolymer nanoparticles
(glyco-SCNPs). A set of water-soluble sub-10 nm-sized glyco-SCNPs
was prepared by thiol-Michael addition cross-linking in water. Bioactivity
of various glucose-conjugated glycopolymers and glyco-SCNPs was evaluated
in binding studies with the glucose-specific lectin Concanavalin A
and by comparing their cellular uptake efficiency in HeLa cells. Cytotoxicity
studies did not reveal discernible cytotoxic effects, making these
SCNPs promising candidates for ligand-based targeted imaging and drug
delivery.
Proteins are biopolymers folded into 3D-structures and are omnipresent in biological systems, where they fulfil a wide array of complex functions. Mimicking the exceptional characteristics of proteins with synthetic analogues...
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