Premium
Relation of Photochemical Internalization to Heat, pH and Ca 2+ Ions
Author(s) -
Soe Tet Htut,
Nanjo Tomotaka,
Watanabe Kazunori,
Ohtsuki Takashi
Publication year - 2019
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13146
Subject(s) - internalization , ion , chemistry , photochemistry , biochemistry , organic chemistry , cell
Abstract The inefficient endosomal escape of drugs or macromolecules is a major obstacle to achieving successful delivery to therapeutic targets. An efficient approach to circumvent this barrier is photochemical internalization (PCI), which uses light and photosensitizers for endosomal escape of the delivered macromolecules. The PCI mechanism is related to photogenerated singlet oxygen, but the mechanism is still unclear. In this study, we examined the relation of PCI to heat, pH and Ca 2+ ions using cell penetrating peptide (CPP)‐cargo‐photosensitizer (Alexa546 or Alexa633) conjugates. A cell temperature changing experiment demonstrated that heat (thermal mechanism) does not significantly contribute to the photoinduced endosomal escape. Inhibition of V‐ATPase proton pump activity and endosomal pH upregulation indicated that PCI‐mediated endosomal escape needs endosomal acidification prior to photoirradiation. Imaging of the CPP‐cargo‐photosensitizer and Ca 2+ ions during photostimulation showed that intracellular calcium increase is not the cause of the endosomal escape of the complex. The increment is mainly due to Ca 2+ influx. These findings show the importance of extra‐ and intracellular milieu conditions in the PCI mechanism and enrich our understanding of PCI‐related changes in cell.