Thermo-responsive polymeric nanoparticles for enhancing neuronal differentiation of human induced pluripotent stem cells

Hye In Seo, Ann Na Cho, Jiho Jang, Dong Wook Kim, Seung Woo Cho, Bong Geun Chung

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


We report thermo-responsive retinoic acid (RA)-loaded poly(N-isopropylacrylamide)-co-acrylamide (PNIPAM-co-Am) nanoparticles for directing human induced pluripotent stem cell (hiPSC) fate. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance analysis confirmed that RA was efficiently incorporated into PNIAPM-co-Am nanoparticles (PCANs). The size of PCANs dropped with increasing temperatures (300-400nm at room temperature, 80-90nm at 37°C) due to its phase transition from hydrophilic to hydrophobic. Due to particle shrinkage caused by this thermo-responsive property of PCANs, RA could be released from nanoparticles in the cells upon cellular uptake. Immunocytochemistry and quantitative real-time polymerase chain reaction analysis demonstrated that neuronal differentiation of hiPSC-derived neuronal precursors was enhanced after treatment with 1-2μg/ml RA-loaded PCANs. Therefore, we propose that this PCAN could be a potentially powerful carrier for effective RA delivery to direct hiPSC fate to neuronal lineage. From the Clinical Editor: The use of induced pluripotent stem cells (iPSCs) has been at the forefront of research in the field of regenerative medicine, as these cells have the potential to differentiate into various terminal cell types. In this article, the authors utilized a thermo-responsive polymer, Poly(N-isopropylacrylamide) (PNIPAM), as a delivery platform for retinoic acid. It was shown that neuronal differentiation could be enhanced in hiPSC-derived neuronal precursor cells. This method may pave a way for future treatment of neuronal diseases.

Original languageEnglish
Pages (from-to)1861-1869
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Issue number7
Publication statusPublished - 2015 Oct 1

Bibliographical note

Funding Information:
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (Grant number HI14C3347); by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2015M3A9D7030461); by a grant (NRF-2010-0020409) from the National Research Foundation of Korea (NRF), funded by the MSIP, Republic of Korea; and in part by a grant (HI14C1588) from the Korea Health Technology R&D Project, funded by the Ministry of Health and Welfare, Republic of Korea.

Publisher Copyright:
© 2015 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science


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