Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Sep 16;3(9):854-857.
doi: 10.1021/mz5004097. Epub 2014 Aug 13.

Synthesis of Acid-Labile PEG and PEG-Doxorubicin-Conjugate Nanoparticles via Brush-First ROMP

Angela X Gao  1 , Longyan Liao  1 , Jeremiah A Johnson  1
Affiliations

Synthesis of Acid-Labile PEG and PEG-Doxorubicin-Conjugate Nanoparticles via Brush-First ROMP

Angela X Gao et al. ACS Macro Lett. .

Abstract

A panel of acid-labile bis-norbornene cross-linkers was synthesized and evaluated for the formation of acid-degradable brush-arm star polymers (BASPs) via the brush-first ring-opening metathesis polymerization (ROMP) method. An acetal-based cross-linker was identified that, when employed in conjunction with a poly(ethylene glycol) (PEG) macromonomer, provided highly controlled BASP formation reactions. A combination of this new cross-linker with a novel doxorubicin (DOX)-branch-PEG macromonomer provided BASPs that simultaneously degrade and release cytotoxic DOX in vitro.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(A) Schematic for the brush-first ROMP process. (B) Acid-labile cross-linkers studied in this report.
Figure 2
Figure 2
Gel permeation chromatography (GPC) traces for N = 10, 15, and 20 BASPs prepared from PEGMM and 5.
Figure 3
Figure 3
LC-MS traces of the N = 0 bottlebrush polymer and N = 15 acetal core BASP after exposure to pH 4.0 buffer for up to 8 d. After this time, 1 drop of concentrated HCl was added to produce the +HCl trace.
Figure 4
Figure 4
(A) Scheme for synthesis of DOX-BASP from DOX-MM and 5. (B) GPC trace of N = 15 DOX-BASP. (C) DLS histograms and negatively stained TEM image (inset) of N = 15 DOX-BASP. Scale bar in TEM image is 100 nm.
Figure 5
Figure 5
HeLa cell viability studies. “ABASP” refers to the acetal-core N = 15 BASP without DOX.
See this image and copyright information in PMC

References

    1. Green J. J.; Langer R.; Anderson D. G. Acc. Chem. Res. 2008, 41, 749. - PMC - PubMed
    1. Gao H.; Matyjaszewski K. Prog. Polym. Sci. 2009, 34, 317.
    1. Webster D. C.; Meier M. A. R.. Polymer Libraries; Springer: New York, 2010; Vol. 225, p 1.
    1. Kreye O.; Toth T.; Meier M. A. R. J. Am. Chem. Soc. 2011, 133, 1790. - PubMed
    1. Hook A. L.; Chang C. Y.; Yang J.; Luckett J.; Cockayne A.; Atkinson S.; Mei Y.; Bayston R.; Irvine D. J.; Langer R.; Anderson D. G.; Williams P.; Davies M. C.; Alexander M. R. Nat. Biotechnol. 2012, 30, 868. - PMC - PubMed