Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 23, 2020
Previous Article Next Article

ABC triblock bottlebrush copolymer-based injectable hydrogels: design, synthesis, and application to expanding the therapeutic index of cancer immunochemotherapy

Author affiliations

Abstract

Bottlebrush copolymers are a versatile class of macromolecular architectures with broad applications in the fields of drug delivery, self-assembly, and polymer networks. Here, the modular nature of graft-through ring-opening metathesis polymerization (ROMP) is exploited to synthesize “ABC” triblock bottlebrush copolymers (TBCs) from polylactic acid (PLA), polyethylene glycol (PEG), and poly(N-isopropylacrylamide) (PNIPAM) macromonomers. Due to the hydrophobicity of their PLA domains, these TBCs self-assemble in aqueous media at room temperature to yield uniform ∼100 nm micelles that can encapsulate a wide range of therapeutic agents. Heating these micellar solutions above the lower critical solution temperature (LCST) of PNIPAM (∼32 °C) induces the rapid formation of multi-compartment hydrogels with PLA and PNIPAM domains acting as physical crosslinks. Following the synthesis and characterization of these materials in vitro, TBC micelles loaded with various biologically active small molecules were investigated as injectable hydrogels for sustained drug release in vivo. Specifically, intratumoral administration of TBCs containing paclitaxel and resiquimod—the latter a potent Toll-like receptor (TLR) 7/8 agonist—into mice bearing subcutaneous CT26 tumors resulted in a significantly enhanced therapeutic index compared to the administration of these two drugs alone. This effect is attributed to the TBC hydrogel maintaining a high local drug concentration, thus reducing systemic immune activation and local inflammation. Collectively, this work represents, to our knowledge, the first example of thermally-responsive TBCs designed for multi-compartment hydrogel formation, establishing these materials as versatile scaffolds for self-assembly and drug delivery.

Graphical abstract: ABC triblock bottlebrush copolymer-based injectable hydrogels: design, synthesis, and application to expanding the therapeutic index of cancer immunochemotherapy

Back to tab navigation

Supplementary files

Article information


Submitted
07 May 2020
Accepted
16 May 2020
First published
01 Jun 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 5974-5986
Article type
Edge Article

ABC triblock bottlebrush copolymer-based injectable hydrogels: design, synthesis, and application to expanding the therapeutic index of cancer immunochemotherapy

F. Vohidov, L. E. Milling, Q. Chen, W. Zhang, S. Bhagchandani, Hung V.-T. Nguyen, D. J. Irvine and J. A. Johnson, Chem. Sci., 2020, 11, 5974
DOI: 10.1039/D0SC02611E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements