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A Photodynamic Approach to Study Function of Intracellular Vesicle Rupture
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Cytosolic delivery of liposomally targeted proteins induced by photochemical internalization

Marjan M Fretz1, Anders Høgset, Gerben A Koning

  • 1Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands.

Pharmaceutical Research
|June 2, 2007
PubMed
Abstract

Insights

Photochemical internalization (PCI) enhances the delivery of targeted liposomal saporin into cells by improving endosomal escape. This technique shows promise for delivering therapeutic proteins to intracellular targets, overcoming limitations of cell entry and degradation.

Area of Science:

  • Biotechnology
  • Cell Biology
  • Drug Delivery

Background:

  • Therapeutic protein delivery is limited by poor cell penetration and lysosomal degradation.
  • Targeted liposomes enhance cellular uptake via endocytosis.
  • Intracellular targets remain inaccessible for many protein therapeutics.

Purpose of the Study:

  • To investigate photochemical internalization (PCI) as a method to enhance endosomal escape for liposomal therapeutic proteins.
  • To assess PCI's efficacy in promoting cytosolic delivery of the cytotoxic protein saporin encapsulated in targeted liposomes.

Main Methods:

  • Saporin was encapsulated in targeted liposomes and applied to human ovarian carcinoma cells pre-treated with a photosensitizer (TPPS2a).
  • Cells were exposed to light to induce photochemical internalization, with varying illumination times and saporin concentrations.
  • Cell viability was measured to determine the cytotoxic effect.

Main Results:

  • Photochemical internalization significantly enhanced the cytotoxic effect of liposomal saporin.
  • Enhanced efficacy was attributed to improved endosomal escape.
  • The cytotoxic effect correlated with the amount of encapsulated saporin and the duration of light exposure.

Conclusions:

  • PCI is a viable strategy for improving the cytosolic delivery of liposomal saporin.
  • The findings suggest PCI's potential applicability to other liposomal therapeutic proteins targeting intracellular components.
  • This approach offers a novel solution to overcome delivery barriers for protein-based therapeutics.

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