Highly swelling pH-responsive microgels for dual mode near infra-red fluorescence reporting and imaging

Mingning Zhu; Dongdong Lu; Qing Lian; Shanglin Wu; Wenkai Wang; L Andrew Lyon; Weiguang Wang; Paulo Bártolo; Mark Dickinson; Brian R Saunders

doi:10.1039/d0na00581a

Highly swelling pH-responsive microgels for dual mode near infra-red fluorescence reporting and imaging

Nanoscale Adv. 2020 Aug 14;2(9):4261-4271. doi: 10.1039/d0na00581a. eCollection 2020 Sep 16.

Authors

Mingning Zhu¹, Dongdong Lu¹, Qing Lian¹, Shanglin Wu¹, Wenkai Wang¹, L Andrew Lyon^{2

3}, Weiguang Wang⁴, Paulo Bártolo⁴, Mark Dickinson⁵, Brian R Saunders¹

Affiliations

¹ Department of Materials, University of Manchester, MSS Tower Manchester M13 9PL UK mingning.zhu@manchester.ac.uk dongdong.lu@manchester.ac.uk brian.saunders@manchester.ac.uk.
² Schmid College of Science and Technology, Chapman University Orange CA 92866 USA.
³ Fowler School of Engineering, Chapman University Orange CA 92866 USA.
⁴ Department of Mechanical, Aerospace and Civil Engineering, School of Engineering, Faculty of Science and Engineering, University of Manchester Manchester M13 9PL UK.
⁵ Photon Science Institute, University of Manchester Oxford Road Manchester M13 9PL UK.

Abstract

Near infra-red (NIR) fluorescence is a desirable property for probe particles because such deeply penetrating light enables remote reporting of the local environment in complex surroundings and imaging. Here, two NIR non-radiative energy transfer (NRET) fluorophores (Cy5 and Cy5.5) are coupled to preformed pH-responsive poly(ethylacrylate-methacrylic acid-divinylbenzene) microgel particles (PEA-MAA-5/5.5 MGs) to obtain new NIR fluorescent probes that are cytocompatible and swell strongly. NIR ratiometric photoluminescence (PL) intensity analysis enables reporting of pH-triggered PEA-MAA-5/5.5 MG particle swelling ratios over a very wide range (from 1-90). The dispersions have greatly improved colloidal stability compared to a reference temperature-responsive NIR MG based on poly(N-isopropylacrylamide) (PNP-5/5.5). We also show that the wavelength of maximum PL intensity (λ _max) is a second PL parameter that enables remote reporting of swelling for both PEA-MAA-5/5.5 and PNP-5/5.5 MGs. After internalization the PEA-MAA-5/5.5 MGs are successfully imaged in stem cells using NIR light. They are also imaged after subcutaneous injection into model tissue using NIR light. The new NIR PEA-MAA-5/5.5 MGs have excellent potential for reporting their swelling states (and any changes) within physiological settings as well as very high ionic strength environments (e.g., waste water).