Ring opening polymerization of α-amino acids: advances in synthesis, architecture and applications of polypeptides and their hybrids

Author(s): Alicia Rasines Mazo ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Stephanie Allison-Logan ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Fatemeh Karimi ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Nicholas Jun-An Chan ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Wenlian Qiu ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Wei Duan ⁶ ^, ⁷ ^, ⁸ ^, ⁵ , Neil M. O’Brien-Simpson ⁹ ^, ¹⁰ ^, ³ ^, ⁴ ^, ⁵ , Greg G. Qiao ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵

Publication date (Electronic): 2020

Journal: Chemical Society Reviews

Publisher: Royal Society of Chemistry (RSC)

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Abstract

This review provides a comprehensive overview of the latest advances in the synthesis, architectural design and biomedical applications of polypeptides and their hybrids.

Abstract

Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and tunable cytocompatibility. Macromolecular design in conjunction with rational monomer composition can direct architecture, self-assembly and chemical behavior, ultimately guiding the choice of appropriate application within the biomedical field. This review focuses on the applications of polypeptides alongside the synthetic advances in the ring opening polymerization of α-amino acid N-carboxyanhydrides achieved in the past five years. Key architectures obtained through NCA ROP or in combination with other polymerization methods are reviewed, as these play an important role in the wide range of applications towards which polypeptides have been applied.

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Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a

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Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.

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Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.