Cytosolic Delivery of Liposomally Targeted Proteins Induced by Photochemical Internalization

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2007 Jun 2

PMID 17541733

Citations 14

Authors

Marjan M Fretz

Anders Hogset

Gerben A Koning

Wim Jiskoot

Gert Storm

Affiliations

Soon will be listed here.

Abstract

Purpose: The application of therapeutic proteins is often hampered by limited cell entrance and lysosomal degradation, as intracellular targets are not reached. By encapsulation of proteins into targeted liposomes, cellular uptake via endocytosis can be enhanced. To prevent subsequent lysosomal degradation and promote endosomal escape, photochemical internalization (PCI) was studied here as a tool to enhance endosomal escape. PCI makes use of photosensitising agents which localize in endocytic vesicles, inducing endosomal release upon light exposure.

Materials And Methods: The cytotoxic protein saporin was encapsulated in different types of targeted liposomes. Human ovarian carcinoma cells were incubated with the photosensitiser TPPS2a and liposomes. To achieve photochemical internalization, the cells were illuminated for various time periods. Cell viability was used as read-out. Illumination time and amount of encapsulated proteins were varied to investigate the influence of these parameters.

Results: The cytotoxic effect of liposomally targeted saporin was enhanced by applying PCI, likely due to enhanced endosomal escape. The cytotoxic effect was dependent on the amount of encapsulated saporin and the illumination time.

Conclusion: PCI is a promising technique for promoting cytosolic delivery of liposomally targeted saporin. PCI may also be applicable to other liposomally targeted therapeutic proteins with intracellular targets.

Citing Articles

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