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Photoinduced Endosomal Escape Mechanism: A View from Photochemical Internalization Mediated by CPP-Photosensitizer

Tet Htut Soe1, Kazunori Watanabe2, Takashi Ohtsuki2

  • 1Department of Biotechnology, Mandalay Technological University, Patheingyi, Mandalay 05072, Myanmar.

Molecules (Basel, Switzerland)
|December 30, 2020
PubMed

Insights

Cell-penetrating peptide (CPP) drug delivery often fails due to endosomal entrapment. Photochemical internalization (PCI) uses light and photosensitizers to enhance endosomal escape, improving drug delivery into the cytosol.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Drug Delivery Systems

Background:

  • Cell-penetrating peptides (CPPs) are crucial for delivering drugs and macromolecules into cells.
  • A major limitation of CPP-based systems is insufficient endosomal escape, leading to cargo degradation.
  • Trapped cargo within endosomes prevents effective cytosolic delivery.

Purpose of the Study:

  • To review the mechanisms of endosomal escape mediated by photochemical internalization (PCI).
  • To discuss the structural design of CPP-photosensitizer conjugates for enhanced delivery.
  • To elucidate the photoinduced endosomal escape mechanism in CPP-based systems.

Main Methods:

  • Review of recent findings on CPP-cargo-photosensitizer conjugates.
  • Analysis of photochemical internalization (PCI) mechanisms.
  • Discussion of structural design principles for CPP-photosensitizer conjugates.

Main Results:

  • Photochemical internalization (PCI) offers a strategy to overcome endosomal entrapment.
  • Light-induced photosensitizer activity destabilizes endosomal membranes.
  • CPP-photosensitizer conjugates facilitate cargo release into the cytosol.

Conclusions:

  • PCI significantly enhances the efficiency of CPP-mediated drug and macromolecule delivery.
  • Understanding the photoinduced mechanism is key to optimizing CPP-based delivery systems.
  • Strategic design of CPP-photosensitizer conjugates is vital for successful therapeutic applications.
Keywords:
cell-penetrating peptideendosomemembranephotochemical internalizationphotosensitizer

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