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

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@mSiO(2)), into which loaded calcium regulators that can either supply or deplete calcium ions. UCNP@mSiO(2) 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-bea