Photochemical internalization (PCI): a technology for drug delivery

Area of Science:

• Biotechnology
• Molecular Biology
• Drug Delivery

Background:

• Macromolecule-based therapies for cancer and other diseases are increasingly important.
• Intracellular delivery to the cell cytosol is often crucial for therapeutic efficacy.
• Endocytic vesicles act as a barrier, hindering cytosolic release of therapeutic macromolecules.

Purpose of the Study:

• To describe a novel technology, photochemical internalization (PCI), for releasing endocytosed macromolecules into the cytosol.
• To detail protocols for PCI of targeted protein toxins and gene therapy vectors.
• To highlight the broad applicability of PCI for various therapeutic agents.

Main Methods:

• PCI utilizes photosensitizers within endocytic vesicles, activated by light.
• Light activation triggers the release of macromolecules from vesicular compartments.
• Protocols cover PCI of EGFR-targeted protein toxins and nonviral polyplex-based gene therapy.

Main Results:

• PCI effectively releases a wide range of macromolecules, including protein toxins, gene plasmids, and chemotherapeutics.
• The technology potentiates the biological activity of molecules that do not readily cross membranes.
• PCI enhances the therapeutic effects of targeted macromolecules.

Conclusions:

• PCI is a versatile technology for enhancing the cytosolic delivery of therapeutic macromolecules.
• The described methodology is applicable to various therapeutic modalities, including gene therapy vectors, nucleic acids, and nanoparticles.
• PCI holds significant promise for improving the treatment of cancer and other diseases.