Near-infrared (NIR) light-triggered pH-manipulation has been realized by utilizing upconversion nanoparticle assisted ring-closing reactions of the conventional photoacid merocyanine (MC). This pH manipulation behavior was then used to regulate the switch of an acid-labile cap for facilitating drug release on the basis of mesoporous silica coated upconversion nanoparticles, in which the drug release rate and amount and the cell killing ability have been greatly improved upon NIR light irradiation due to the locally high concentration of H+ within pore channels that is generated by upconversion assisted MC. This proof of concept may provide a way to utilize NIR light to regulate pH change for new drug delivery system designs and applications in biomedical field. (C) 2020 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.