Molecular polymer bottlebrushes in nanomedicine: therapeutic and diagnostic applications

Müllner, Markus

doi:10.1039/d2cc01601j

Cited by 31 publications

(19 citation statements)

References 210 publications

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“…This causes an undesired accumulation of the drug in other healthy organs with serious side effects. To solve this critical issue, polymer-based nanoparticles such as drug-conjugated polymer chains, polymeric micelles, polymersomes, and molecular bottlebrushes , have been proposed as drug carriers and studied for decades. Nanoparticles in the appropriate size range are expected to accumulate at tumor sites by leaking from underdeveloped endothelial blood vessels around the tumor tissue and be retained for days .…”

Section: Introductionmentioning

confidence: 99%

Zwitterionic Amino Acid Polymer-Grafted Core-Crosslinked Particle toward Tumor Delivery

Fujii

Sakurai

2022

Biomacromolecules

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Zwitterionic amino acid polymers (ZAPs) exhibit biocompatibility and recognition capability for amino acid transporters (AATs) overexpressed on cancer cells. They are potential cancer-targeting ligands in nanoparticle-based nanomedicines utilized in cancer chemotherapy. Here, a poly(glutamine methacrylate) (pGlnMA)-grafted core-crosslinked particle (pGlnMA-CCP) is prepared through the formation of nanoemulsions stabilized using amphiphilic block copolymers comprising pGlnMA as the hydrophilic block. The chain conformation of the grafted polymer and the particle structure of pGlnMA-CCP are precisely elucidated by dynamic light scattering, X-ray scattering, and transmission electron microscopy. pGlnMA-CCP demonstrates active cellular uptake and deep penetration behaviors for cancer cells and spheroids, respectively, via an AAT-mediated mechanism. The in vivo pharmacokinetics of pGlnMA-CCP is practically comparable to those of a CCP covered with poly(polyethylene glycol methacrylate) (pPEGMA), which inhibits protein adsorption and prolongs blood retention, implying that the biocompatible properties of pGlnMA are similar to those of pPEGMA. Furthermore, pGlnMA-CCP accumulates in cancer tissues at a higher level than that of pPEGMA systems. The results demonstrate that the properties of cancer targetability, tumor permeability, efficient tumor accumulation, and biocompatibility can be obtained by grafting pGlnMA onto nanoparticles, suggesting a high potential of pGlnMA as a ligand for cancer-targeting nanomedicines.

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Section: Introductionmentioning

confidence: 99%

Zwitterionic Amino Acid Polymer-Grafted Core-Crosslinked Particle toward Tumor Delivery

Fujii

Sakurai

2022

Biomacromolecules

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“…Bottlebrush polymers (BBPs) possess distinct physical properties derived from oligomeric or polymeric side chains which are densely attached to their linear polymer backbone. [1][2][3] In particular, bottlebrush block copolymers (BBCPs) have recently attracted attention as macromolecular building blocks for the creation of nanostructures with large chemically distinct domains that are promising candidates for use in photonics, [4][5][6][7][8][9][10] coatings, 11,12 drug delivery, [13][14][15] imaging, [16][17][18] patterning, 19,20 and antifouling [21][22][23][24] applications.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of discrete bottlebrush polymers via the iterative convergent growth technique and post-functionalization

Jisu

et al. 2022

Polym. Chem.

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“…Because MB length, thickness, and rigidity can be easily tuned, they found use in a wide range of biomedical applications . MBs can serve as effective carriers of therapeutic cargo, − scaffolds for injectable hydrogels, − effective lubricants, − and antifouling agents. ,, Currently, polyethylene glycol (PEG) and its derivative (meth)acrylates are the polymers of choice in biomedical applications due to their biocompatibility and “stealth” properties .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Biocompatible Sulfoxide-Containing Molecular Bottlebrushes

Olszewski

Phạm

Bolívar

et al. 2022

ACS Appl. Polym. Mater.

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Macromolecular bottlebrushes (MBs) are emerging as an attractive polymer architecture for biomedical applications. Herein, synthesis and characterization of sulfoxide-containing water-soluble MBs with poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA) side chains with varying grafting densities are reported. Highly hydrophilic PMSEA side chains were prepared by grafting-from poly(2-bromoisobutyryloxyethyl methacrylate) (PBiBEM) using photoATRP with either CuBr2/TPMA (tris(2-pyridylmethyl)amine), CuBr2/TPMA*3 (tris([(4-methoxy-2,5-dimethyl)-2-pyridyl]methyl)amine), or CuBr2/Me6TREN (tris(2-dimethylaminoethyl)amine), which were photochemically reduced to the appropriate amount of activators CuBr/ligand to start atom transfer radical polymerization (ATRP). Kinetic experiments showed that the polymerization was the fastest using CuBr2/Me6TREN at 6-fold excess of ligand to Cu. Additionally, the increase of ligand concentration resulted in a faster reaction with CuBr2/Me6TREN. A series of PMSEA MBs with grafting densities of 30%, 50%, and 100% was synthesized. The PMSEA MBs exhibited tunable hydrodynamic lubrication properties and low cytotoxicity against different types of cells. PMSEA MBs reveal rheological properties characteristic for nonentangled polymer melts. Densely grafted PMSEA MBs showed a nonlinear relationship between the coefficient of friction and the applied force.

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Molecular polymer bottlebrushes in nanomedicine: therapeutic and diagnostic applications

Abstract: Molecular polymer bottlebrushes offer a comprehensive toolbox for nanomaterials design. Their tuneable and multifunctional architecture has accelerated their use in nano-bio research and nanomedicine applications.

Cited by 31 publications

References 210 publications

Zwitterionic Amino Acid Polymer-Grafted Core-Crosslinked Particle toward Tumor Delivery

Zwitterionic Amino Acid Polymer-Grafted Core-Crosslinked Particle toward Tumor Delivery

Synthesis of discrete bottlebrush polymers via the iterative convergent growth technique and post-functionalization

Synthesis and Characterization of Biocompatible Sulfoxide-Containing Molecular Bottlebrushes

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