Near-infrared light-controlled regulation of intracellular calcium to modulate macrophage polarization

Heemin Kang, Kunyu Zhang, Dexter Siu Hong Wong, Fengxuan Han, Bin Li, Liming Bian

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

Macrophages are multifunctional immune cells with diverse physiological functions such as fighting against infection, influencing progression of pathologies, maintaining homeostasis, and regenerating tissues. Macrophages can be induced to adopt distinct polarized phenotypes, such as classically activated pro-inflammatory (M1) phenotypes or alternatively activated anti-inflammatory and pro-healing (M2), to execute diverse and dynamic immune functions. However, unbalanced polarizations of macrophage can lead to various pathologies, such as atherosclerosis, obesity, tumor, and asthma. Thus, the capability to remotely control macrophage phenotypes is important to the success of treating many pathological conditions involving macrophages. In this study, we developed an upconversion nanoparticle (UCNP)-based photoresponsive nanocarrier for near-infrared (NIR) light-mediated control of intracellular calcium levels to regulate macrophage polarization. UCNP was coated with mesoporous silica (UCNP@mSiO2), into which loaded calcium regulators that can either supply or deplete calcium ions. UCNP@mSiO2 was chemically modified through serial coupling of photocleavable linker and Arg-Gly-Asp (RGD) peptide-bearing molecular cap via cyclodextrin-adamantine host-guest complexation. The RGD-bearing cap functioned as the photolabile gating structure to control the release of calcium regulators and facilitated the cellular uptake of UCNP@mSiO2 nanocarrier. The upconverted UV light emission from the UCNP@mSiO2 under NIR light excitation triggered the cleavage of cap and intracellular release of calcium regulators, thereby allowing temporal regulation on the intracellular calcium levels. Application of NIR light through skin tissue promoted M1 or M2 polarization of macrophages, by elevating or depleting intracellular calcium levels, respectively. To the best of our knowledge, this is the first demonstration of NIR light-mediated remote control on macrophage polarization. This photoresponsive nanocarrier offers the potential to remotely manipulate in vivo immune functions, such as inflammation or tissue regeneration, via NIR light-controlled macrophage polarization.

Original languageEnglish
Pages (from-to)681-696
Number of pages16
JournalBiomaterials
Volume178
DOIs
Publication statusPublished - 2018 Sept
Externally publishedYes

Bibliographical note

Funding Information:
Project 31570979 and 81471790 is supported by the National Natural Science Foundation of China. The work described in this paper is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project no. 14202215, 14220716). This work is supported by the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (reference no.: 04152836, 03140056). This research was also supported by the project BME-p3-15 of the Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong. This research is supported by the Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong. We are grateful for technical support from Josie Lai, Samuel Wong, and Anny Cheung in the School of Biomedical Sciences, The Chinese University of Hong Kong. We also thank Prof. Feng Wang and Ms. Tianying Sun in the Department of Materials Science and Engineering, City University of Hong Kong, for the help with the photoluminescence characterization of the UCNPs.

Funding Information:
Project 31570979 and 81471790 is supported by the National Natural Science Foundation of China . The work described in this paper is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project no. 14202215 , 14220716 ). This work is supported by the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (reference no.: 04152836 , 03140056 ). This research was also supported by the project BME-p3-15 of the Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong . This research is supported by the Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong . We are grateful for technical support from Josie Lai, Samuel Wong, and Anny Cheung in the School of Biomedical Sciences, The Chinese University of Hong Kong. We also thank Prof. Feng Wang and Ms. Tianying Sun in the Department of Materials Science and Engineering, City University of Hong Kong, for the help with the photoluminescence characterization of the UCNPs.

Publisher Copyright:
© 2018 Elsevier Ltd

Keywords

  • Calcium regulation
  • Macrophage polarization
  • Near-infrared light control
  • Photocleavable cap
  • Upconversion nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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