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
Review
. 2025 Aug;41(8):1251-1267.
doi: 10.1007/s44211-025-00785-x. Epub 2025 May 23.

Temperature-modulated separation of therapeutic cells, viral vectors, and exosomes using functional polymers

Kenichi Nagase  1 , Hideko Kanazawa  2
Affiliations
Review

Temperature-modulated separation of therapeutic cells, viral vectors, and exosomes using functional polymers

Kenichi Nagase et al. Anal Sci. 2025 Aug.

Abstract

In recent decades, advanced therapeutic modalities such as therapeutic cells, viral vectors, and extracellular vesicles (exosomes), have emerged as effective therapies for intractable diseases. These therapeutic modalities produced through bioprocesses must be purified from contaminants. Effective separation methods are essential for optimizing therapeutic modalities. This review highlights innovative temperature-modulated separation methods enabled by the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAAm). The design of PNIPAAm-modified interfaces plays a pivotal role in ensuring precise and efficient separation. We summarize the recent advancements in the application of temperature-modulated separation methods for cells, viral vectors, and exosomes, with a focus on the design of PNIPAAm interfaces.

Keywords: Biomaterials; Polymer brush; Regenerative medicine; Temperature-responsive chromatography; Thermoresponsive interface; Thermoresponsive polymer.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: There are no competing interests to declare.

Figures

Fig. 1
Fig. 1
Illustration of A temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and B PNIPAAm brush-modified interfaces
Fig. 2
Fig. 2
Temperature-modulated cell separation using thermoresponsive ionic polymer brushes. A UCMSC separation using a thermoresponsive cationic block copolymer brush-grafted glass substrate B BMMSC separation from differentiated adipocytes using a mixed polymer brush composed of PNIPAAm- and PDMAPAAm-modified glass substrates
Fig. 3
Fig. 3
Temperature-modulated cell separation using thermoresponsive affinity polymer brushes. A Vascular cell separation using peptide-conjugated thermoresponsive block copolymer brush-grafted glass substrate and B hepatocyte separation using thermoresponsive glycopolymer block copolymer brush-grafted glass substrate
Fig. 4
Fig. 4
Temperature-modulated cell separation column. A Illustration of the cell separation column using thermoresponsive cationic block copolymer brush-grafted beads and B cell composition at each fraction
Fig. 5
Fig. 5
Temperature-modulated viral vector purification. A Illustration of packing materials for the purification column and B purification procedure and virus elution at two temperatures
Fig. 6
Fig. 6
Temperature-modulated capture of exosomes using a thermoresponsive block copolymer brush with affinity peptides
See this image and copyright information in PMC

References

    1. M. Heskins, J.E. Guillet, Solution properties of poly(N-isopropylacrylamide). J. Macromol. Sci. A 2, 1441–1455 (1968). 10.1080/10601326808051910
    1. E.S. Gil, S.M. Hudson, Stimuli-reponsive polymers and their bioconjugates. Prog. Polym. Sci. 29, 1173–1222 (2004). 10.1016/j.progpolymsci.2004.08.003
    1. A. Halperin, M. Kröger, F.M. Winnik, Poly(N-isopropylacrylamide) phase diagrams: fifty years of research. Angew. Chem. Int. Ed. 54, 15342–15367 (2015). 10.1002/anie.201506663 - PubMed
    1. K. Nagase, T. Onuma, M. Yamato, N. Takeda, T. Okano, Enhanced wettability changes by synergistic effect of micro/nanoimprinted substrates and grafted thermoresponsive polymer brushes. Macromol. Rapid Commun. 36, 1965–1970 (2015). 10.1002/marc.201500393 - PubMed
    1. K. Nagase, J. Matsuda, A. Takeuchi, Y. Ikemoto, Hydration and dehydration behaviors of poly(N-isopropylacrylamide)-grafted silica beads. Surf. Interf. 40, 103058 (2023). 10.1016/j.surfin.2023.103058

LinkOut - more resources