Bottlebrush polymers with flexible enantiomeric side chains display differential biological properties

Nguyen, Hung V.-T.; Jiang, Yivan; Mohapatra, Somesh; Wang, Wencong; Barnes, Jonathan C.; Oldenhuis, Nathan J.; Chen, Kathleen K.; Axelrod, Simon; Huang, Zhihao; Chen, Qixian; Golder, Matthew R.; Young, Katherine; Suvlu, Dylan; Yizhi, Shen,; Willard, Adam P.; Hore, Michael J. A.; Gómez‐Bombarelli, Rafael; Johnson, Jeremiah A.

doi:10.1038/s41557-021-00826-8

Cited by 47 publications

(54 citation statements)

References 49 publications

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“…Most recently, Johnson et al reported polymers with enantiomeric side chains displaying changed cellular uptakes and pharmacokinetic properties due to their different chiral recognition. 15 Our group also observed significant changes in the protein delivery efficiency from modified guanidine groups. Using various carbamoylated guanidine (CG) derivatives, we demonstrated the importance of the newly developed functional group for complex serum stability, cellular entry, and cytosolic availability of proteins.…”

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confidence: 64%

Effects of sidechain isomerism on polymer-based non-covalent protein delivery

et al. 2022

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confidence: 64%

Effects of sidechain isomerism on polymer-based non-covalent protein delivery

et al. 2022

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“…Overall, the effect of the polymer chirality of drug (chiral or achiral) solubilization was found to be minor, if existent. Considering the work of Nguyen et al, 9 we posit that this may be due to the rather limited mobility of the polymer chains at the chiral centers. We hypothesize that the fact that the chiral centers are in the backbone, the surrounding molecules and the environment cannot properly interact with this part of the polymer; therefore the effect of the chirality beyond the secondary structure formation is minute.…”

Section: Macromolecules Pubsacsorg/macromolecules Articlementioning

confidence: 91%

“…Nguyen et al developed sets of chiral bottlebrush polymers (CBPs) based on unimolecular norbornene-terminated macromonomers (MMs) with different stereochemistry and rigidity. 9 The stereoregularity influenced the CBPs with flexible chiral side chains remarkably in cytotoxicity, cell uptake, blood pharmacokinetics, and liver clearance. However, the CBPs with a comparably rigid chiral side chain did not show an obvious difference between isomers.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Investigation of Chiral Poly(2,4-disubstituted-2-oxazoline)-Based Triblock Copolymers, Their Self-Assembly, and Formulation with Chiral and Achiral Drugs

Yang¹,

Haider²,

Forster³

et al. 2022

Macromolecules

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Considering the largely chiral nature of biological systems, there is interest in chiral drug delivery systems. Here, we investigate for the first time polymer micelles based on poly(2-oxazoline) (POx) ABA-type triblock copolymers with chiral and racemic hydrophobic blocks for the formulation of chiral and achiral drugs. Specifically, poly(2-ethyl-4-ethyl-2oxazoline) (pEtEtOx) and poly(2-propyl-4-methyl-2-oxazoline) (pPrMeOx) were used as hydrophobic block B and poly(2-methyl-2-oxazoline) (pMeOx) as hydrophilic block A. Using these triblock copolymers, nanoformulations of curcumin (CUR), paclitaxel (PTX), and chiral (R and S) and racemic ibuprofen were prepared. For CUR and PTX, the maximum drug loading was significantly dependent on the structure of the hydrophobic repeat units, but not the chirality. In contrast, the maximum drug loading with chiral/racemic ibuprofen was affected neither by the polymer structure nor by chirality, but minor effects were observed with respect to the size and size distribution of the drug-loaded micelles.

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“…[17][18][19]240,241 Cylindrical structures of BBPs can increase the retention of drug molecules and cell-or tissue-selective targeting. 17,242 The high functionality of BBPs affords a large loading of drug molecules, as they can be readily attached to the end groups of sidechains 18 or coupled to the backbone. 240,241 These advantages have led to rigorous research into applying BBPs in the drug delivery field.…”

Section: Solution Assembly and Drug Deliverymentioning

confidence: 99%