Proteins Conjugated with Sulfoxide-Containing Polymers Show Reduced Macrophage Cellular Uptake and Improved Pharmacokinetics

Yu, Yanmin; Xu, Weizhi; Huang, Xumin; Xu, Xin; Qiao, Ruirui; Li, Yuhuan; Han, Felicity Y.; Peng, Hui; Davis, Thomas P.; Fu, Changkui; Whittaker, Andrew K.

doi:10.1021/acsmacrolett.0c00291

Cited by 36 publications

(38 citation statements)

References 51 publications

(71 reference statements)

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“…However, the difference between the wetting of PSO and PSO2 was limited. The increased hydrophilicity of the oxidized derivatives was due to dipolar interactions between the polymer chains and the solvent and could potentially be harnessed in the design of biomaterials for in vivo applications. ,− …”

Section: Resultsmentioning

confidence: 99%

Selective Oxidation of Polysulfide Latexes to Produce Polysulfoxide and Polysulfone in a Waterborne Environment

2021

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Polymers containing sulfur centers with high oxidation states in the main chain, polysulfoxide and polysulfone, display desirable properties such as thermomechanical and chemical stability. To circumvent their challenging direct synthesis, methods based on the oxidation of a parent polysulfide have been developed but are plagued by uncontrolled reactions, leading either to ill-defined mixtures of polysulfoxides and polysulfones or to polysulfones with reduced degrees of polymerization due to overoxidation of the polymer. We developed an alternative method to produce well-defined polysulfoxide and polysulfone in a waterborne colloidal emulsion using different oxidants to control the oxidation state of sulfur in the final materials. The direct oxidation of water-based polysulfide latexes avoided the use of volatile organic solvents and allowed for the control of the oxidation state of the sulfur atoms. Oxidation of parent polysulfides by tert -butyl hydroperoxide led to the production of pure polysulfoxides, even after 70 days of reaction time. Additionally, hydrogen peroxide produced both species through the course of the reaction but yielded fully converted polysulfones after 24 h. By employing mild oxidants, our approach controlled the oxidation state of the sulfur atoms in the final sulfur-containing polymer and prevented any overoxidation, thus ensuring the integrity of the polymer chains and colloidal stability of the system. We also verified the selectivity, versatility, and robustness of the method by applying it to polysulfides of different chemical compositions and structures. The universality demonstrated by this method makes it a powerful yet simple platform for the design of sulfur-containing polymers and nanoparticles.

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Section: Resultsmentioning

confidence: 99%

Selective Oxidation of Polysulfide Latexes to Produce Polysulfoxide and Polysulfone in a Waterborne Environment

2021

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“…As a highly biocompatible polymer, PEG has gained significant reputation for conferring low-fouling property in many biomedical applications. − However, PEG has amphiphilic character and has been reported to interact with certain proteins to form weak complexes through hydrophobic interactions, − potentially limiting its antifouling capability. This has led to the development of alternative candidate polymers such as zwitterionic polymers, − poly(2-oxazoline)s, − and peptides and peptoids. − Recently, sulfoxide polymers have emerged as a new class of low-fouling polymer. − As a result of the presence of a large number of highly polar sulfoxide groups, sulfoxide polymers demonstrate exceptional solubility in water and are able to impart superior low-fouling behavior to a variety of entities such as nanoparticles and biomolecules. ,− For instance, our recent research has revealed that iron oxide nanoparticles coated with sulfoxide polymers circulate longer in the bloodstream of mice and resist being rapidly captured by the mononuclear phagocyte system . In addition, these nanoparticles show reduced adsorption of proteins, which mitigates the formation of the so-called protein corona.…”

Section: Introductionmentioning

confidence: 99%

Antifouling Surfaces Enabled by Surface Grafting of Highly Hydrophilic Sulfoxide Polymer Brushes

Huang

Chang

et al. 2020

Biomacromolecules

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Antifouling surfaces are important in a broad range of applications. An effective approach to antifouling surfaces is to covalently attach antifouling polymer brushes. This work reports the synthesis of a new class of antifouling polymer brushes based on highly hydrophilic sulfoxide polymers by surface-initiated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The sulfoxide polymer brushes are able to effectively reduce nonspecific adsorption of proteins and cells, demonstrating remarkable antifouling properties. Given the outstanding antifouling behavior of the sulfoxide polymers and versatility of surface-initiated PET-RAFT technology, this work presents a useful and general approach to engineering various material surfaces with antifouling properties, for potential biomedical applications in areas such as tissue engineering, medical implants, and regenerative medicine.

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“…Zwitterionic polymers are nonfouling in nature and offer higher chemical diversity for exosome-based materials (51). A recent report that a pMSEA polymer can reduce macrophage uptake of a protein polymer hybrid provides another example of a polymer enhancing the biochemical profile in a polymer biohybrid (31,52). Grafting of cationic polymers such as pDMAEMA onto the exosome surface can also offer a wide variety of responsive hybrids and therapeutic materials.…”

Section: Discussionmentioning

confidence: 99%

Engineering exosome polymer hybrids by atom transfer radical polymerization

Lathwal

Yerneni

Boye

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Exosomes are emerging as ideal drug delivery vehicles due to their biological origin and ability to transfer cargo between cells. However, rapid clearance of exogenous exosomes from the circulation as well as aggregation of exosomes and shedding of surface proteins during storage limit their clinical translation. Here, we demonstrate highly controlled and reversible functionalization of exosome surfaces with well-defined polymers that modulate the exosome’s physiochemical and pharmacokinetic properties. Using cholesterol-modified DNA tethers and complementary DNA block copolymers, exosome surfaces were engineered with different biocompatible polymers. Additionally, polymers were directly grafted from the exosome surface using biocompatible photo-mediated atom transfer radical polymerization (ATRP). These exosome polymer hybrids (EPHs) exhibited enhanced stability under various storage conditions and in the presence of proteolytic enzymes. Tuning of the polymer length and surface loading allowed precise control over exosome surface interactions, cellular uptake, and preserved bioactivity. EPHs show fourfold higher blood circulation time without altering tissue distribution profiles. Our results highlight the potential of precise nanoengineering of exosomes toward developing advanced drug and therapeutic delivery systems using modern ATRP methods.

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Proteins Conjugated with Sulfoxide-Containing Polymers Show Reduced Macrophage Cellular Uptake and Improved Pharmacokinetics

Cited by 36 publications

References 51 publications

Selective Oxidation of Polysulfide Latexes to Produce Polysulfoxide and Polysulfone in a Waterborne Environment

Selective Oxidation of Polysulfide Latexes to Produce Polysulfoxide and Polysulfone in a Waterborne Environment

Antifouling Surfaces Enabled by Surface Grafting of Highly Hydrophilic Sulfoxide Polymer Brushes

Engineering exosome polymer hybrids by atom transfer radical polymerization

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