Light-induced physicochemical alterations of photoacid-containing nanogels allow spatiotemporal control over their cellular uptake

  • J Control Release. 2026 Jun 10:394:114892. doi: 10.1016/j.jconrel.2026.114892.
Yanjing Ji  1 ,  Gianni Pacella  2 ,  Jan Hoekstra  1 ,  Ed de Jong  1 ,  Giuseppe Portale  3 ,  Patrick van Rijn  4
Affiliations
  • 1. Department of Biomaterials and Biomedical Technology, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV, Groningen, the Netherlands.
  • 2. Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 3, 9747 AG, Groningen, the Netherlands.
  • 3. Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 3, 9747 AG, Groningen, the Netherlands. Electronic address: [email protected].
  • 4. Department of Biomaterials and Biomedical Technology, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV, Groningen, the Netherlands. Electronic address: [email protected].
PMID: 41932367 DOI: 10.1016/j.jconrel.2026.114892
Abstract

Cellular uptake plays an important role in efficient drug delivery, and conventional approaches are capable of regulation of cellular uptake but do not provide spatiotemporal precision. In this study, visible light-responsive photoacid-based nanogels (PA nGels) are developed with the aim of achieving dynamic control over cellular uptake. The physicochemical properties (particle size, zeta potential, stiffness, and reversibility) of these nanogels under visible light irradiation are systematically investigated. This study investigates the intracellular uptake efficiency of PA nGels by human gingival fibroblasts, a key cell type in periodontal tissues, to elucidate the relationships among their structure, properties, and functions. It has been demonstrated that under light irradiation, nanogels containing PA moieties exhibited conformational transitions in size and zeta potential. These alterations are ascribed to the equilibrium between volume, surface charge and hydrophilicity. The results of cellular uptake experiments demonstrate that the uptake is influenced when the PA nGels are irradiated, increasing the intracellular uptake. This study proposes a rational strategy for enhancing cellular uptake efficiency, with the potential to improve drug delivery to target cells.

Keywords
Conformational transition; Endocytosis; Human gingival fibroblasts; Light-responsive nanogels.
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