Tuning the Hydrophilic-Hydrophobic Balance of Molecular Polymer Bottlebrushes Enhances their Tumor Homing Properties

Parathan Ramamurthi; Zhongchao Zhao; Eamonn Burke; Nicole F Steinmetz; Markus Müllner

doi:10.1002/adhm.202200163

Tuning the Hydrophilic-Hydrophobic Balance of Molecular Polymer Bottlebrushes Enhances their Tumor Homing Properties

Adv Healthc Mater. 2022 Jun;11(12):e2200163. doi: 10.1002/adhm.202200163. Epub 2022 Feb 27.

Authors

Parathan Ramamurthi¹, Zhongchao Zhao^{2

3}, Eamonn Burke¹, Nicole F Steinmetz^{2

3

4

5

6}, Markus Müllner^{1

7}

Affiliations

¹ Key Centre for Polymers and Colloids, School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia.
² Department of NanoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92039, USA.
³ Center for Nano-ImmunoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92039, USA.
⁴ Department of Bioengineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92039, USA.
⁵ Department of Radiology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92039, USA.
⁶ Moores Cancer Center, Institute for Materials Discovery and Design, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92039, USA.
⁷ The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Sydney, NSW, 2006, Australia.

Abstract

Nanoparticle (NP)-based drug delivery systems are promising in anticancer therapy, capable of delivering cargo with superior selectivity and achieving enhanced tumor accumulation compared to small-molecule therapeutics. As more efforts are being devoted to NP development, molecular polymer bottlebrushes (MPBs) have gained attention as a potential drug delivery vehicle. To date, the influence of various MPB parameters such as size, shape, and surface charge in determining tumor penetrability have been systematically probed. However, the role of amphiphilicity, specifically the hydrophilic-hydrophobic balance, remains unexplored. In this study, a series of MPBs are employed with varied hydrophobicity levels to reveal a dependence between MPB composition, cell association, and tumor homing. The data indicates that increasing levels of hydrophobicity in MPBs (to a certain level) demonstrate only marginal effects in vitro but reveals enhanced tumor homing in a mouse model of ovarian cancer in vivo, where more hydrophilic MPBs exhibit low tissue deposition and low tumor homing. In contrast, more hydrophobic MPBs show significant tumor accumulation and homing due to their engineered hydrophobicity.

Keywords: 3D cell culture; biodistribution; cellular interactions; polymer bottlebrushes; polymer nanoparticles; tumor mouse model.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Drug Delivery Systems
Hydrophobic and Hydrophilic Interactions
Mice
Nanoparticles* / chemistry
Neoplasms* / drug therapy
Polymers / chemistry

Substances

Polymers

Abstract

Publication types

MeSH terms

Substances

Grants and funding