The recent progress of novel polypeptoid materials and biomedical applications

Polypeptoids are a type of novel biomedicine polymer materials with excellent biocompatibility. Polypeptoids have backbones similar to that of polypeptides, except that their pendant chains are attached to the nitrogen atoms. Thus, polypeptoids lack chiral centers and –NH···O=C– hydrogen bonding along the backbone. Polypeptoids can be synthesized using two typical approaches, the solid-phase submonomer synthesis method and the ring-opening polymerization (ROP). In contrast to the former that offers sequence specificity, near-absolute monodispersity, but with short chain length and low yield, controlled ROP offers polypeptoids with high molecular weights and high yields. Lately, stimuli-responsive polypeptoids have received increasing attention because of their promising applications in biotechnology owing to their biocompatibility, biodegradability, and bioactivity. The properties of polypeptoids are mainly dominated by the sidechain identity, which offers a unique and facile way to tailor the properties of the polymers by structural design of the side chains. A few types of stimuli-responsive polypeptoids, such as thermoresponsive, photoresponsive, and redox-responsive polypeptoid-based polymers, were typically prepared by ROP of functional monomers and post-modification of the well-defined precursors. Thermoresponsive polypeptoids are capable to exhibit a reversible phase transition in a controlled manner to temperature. They have great potential for biomedical applications, such as drug carriers, smart hydrogels and stimuli-responsive surfaces. The thermoresponsive polypeptoid containing oligo(ethylene glycol) (OEG), amino and carboxyl group was synthesized using post-modification. Photoresponsive polypeptoids have received considerable attention as a class of promising smart materials. Due to their high selectivity and efficiency, photoresponsive polypeptoids offer excellent potential in drug delivery, polymer therapeutics, and smart surfaces. The o -nitrobenzyl group has received increasing attention due to its good stability under acidic and basic conditions and highly controllable photochemical properties. The photoresponsive polypeptoid with o -nitrobenzyl group was prepared using ROP of functional monomers. The redox-responsive polypeptoids have drawn considerable attention recently due to their potential applications in drug and gene delivery, especially for cancer therapy. The most extensively investigated redox-responsive groups are based on thiol chemistry, such as the disulfide bond and the thioether group. The nanostructured polypeptoids show great potential for biological and chemical applications. The diblock copolypeptoids can self-assemble to form a variety of nanostructures due to their capacity of microphase separation and crystallization. For example, the poly(ethylene glycol)- block -poly( N -octylglycine) (PEG- b -PNOG) could form a 2D nanosheet structure, which is driven by the crystallization of PNOG block in a selective solvent. In addition, the poly(ethyl glycol)- block -poly(L-glutamic acid)- block -poly( N -octylglycine) (PEG- b -PGA- b -PNOG) triblock copolymers could form the nanodisks and nanosheets at different pH, which is driven by the hydrophobicity of the PNOG blocks. Further, the amphiphilic poly( N -allylglycine)- b -poly( N -octylglycine) (PNAG- b -PNOG) conjugated with thiol-terminated triethylene glycol monomethyl ethers ((PNAG- g -EG3)- b -PNOG) in aqueous solution could assemble different nanostructures. Specifically, the thermoresponsive property of PNAG- g -EG3 initiates the assembly process, promoted by subsequent crystallization of PNOG and physically locks the morphology eventually. The peptoid prepared using the solid-phase submonomer synthesis method results in the formation of giant, free-floating sheets with thickness of only 2.7 nm in aqueous solution. Polypeptoids possess substantial flexibility of the main chain, good solubility, and enzymatic stability, showing great potential in biomedical applications, such as antimicrobial, antifouling, gene transfection, drug delivery and therapeutics. In this article, we will discuss the recent progress of polypeptoids and their biomedical applications. The polypeptoid possess substantial flexibility of the main chain, good solubility, and enzymatic stability, which show great potential for the biomedical applications, such as antimicrobial, antifouling, gene transfection, drug delivery and therapeutics. In this review, we will discuss the recent progress of the polypeptoid and biomedical applications.