Influence of size, crosslinking degree and surface structure of poly(N-vinylcaprolactam)-based microgels on their penetration into multicellular tumor spheroids

Changchang Zhang; Elisabeth Gau; Wenjie Sun; Jianzhi Zhu; Ben Michael Schmidt; Andrij Pich; Xiangyang Shi

doi:10.1039/C9BM01132C

Influence of size, crosslinking degree and surface structure of poly(N-vinylcaprolactam)-based microgels on their penetration into multicellular tumor spheroids†

Changchang Zhang,‡^a Elisabeth Gau,

‡^bc Wenjie Sun,^a Jianzhi Zhu,^a Ben Michael Schmidt,^bc Andrij Pich

*^bcd and Xiangyang Shi

*^a

Author affiliations

* Corresponding authors

^a State Key Laboratory for Modification of Chemical Fiber and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-dimension Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China
E-mail: xshi@dhu.edu.cn

^b Functional and Interactive Polymers, Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, Aachen, Germany
E-mail: pich@dwi.rwth-aachen.de

^c DWI – Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen, Germany

^d Aachen Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD Geleen, The Netherlands

Abstract

Current nanomedicine suffers from a big challenge due to the fact that most of the nanocarrier systems lack the desired tumor penetration depth, thereby limiting their clinical translation. Unlike the nanomaterials with a similar size or shape, microgels display excellent softness, fluidity and deformability, as well as stimuli-responsiveness in the tumor microenvironment. Herein, we report the synthesis of temperature-responsive poly(N-vinylcaprolactam)/oligo (ethylene glycol) acrylate/glycidyl methacrylate (PVCL/OEGA/GMA) microgels with different hydrodynamic radii (100–500 nm), crosslinking densities, 2-methoxyethyl acrylate (MEA) contents and OEGA chain lengths using a precipitation polymerization method and the investigation of the microgels in terms of their tumor penetration capability using a multicellular tumor spheroid (MCTS) model. The prepared microgels were well characterized with different techniques. We show that regardless of the size, crosslinking density, MEA content and OEGA chain length, all microgels display the desired cytocompatibility in the given concentration range. In vitro cellular uptake data reveal that similar to 2-dimensional (2-D) adherent cells, microgels with a smaller size display more enhanced cellular uptake than those having a larger size in the 3-D MCTS model. Likewise, 3-D MCTS penetration results indicate that the PVCL/OEGA/GMA microgels with the smallest radius of 100 nm exhibit the deepest penetration length. We then selected the microgels with a radius of 200 nm but with different physicochemical parameters to investigate their cellular uptake and tumor penetration behavior. Our data show that microgels with varying crosslinking densities, MEA contents and OEGA chain lengths do not have any appreciable changes in terms of their cellular uptake and penetration in the 3-D MCTS model. Our study provides new insights for the design of different microgel-based systems for further cancer theranostic applications.

Biomaterials Science

Influence of size, crosslinking degree and surface structure of poly(N-vinylcaprolactam)-based microgels on their penetration into multicellular tumor spheroids†

Abstract

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Influence of size, crosslinking degree and surface structure of poly(N-vinylcaprolactam)-based microgels on their penetration into multicellular tumor spheroids

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