Abstract
Photochemical internalisation (PCI) is a technique for improving cellular delivery of certain bioactive agents which are prone to sequestration within endolysosomes. There is a wide range of agents suitable for PCI‐based delivery including toxins, oligonucleotides, genes and immunoconjugates which demonstrates the versatility of this technique. The basic mechanism of PCI involves triggering release of the agent from endolysosomes within the target cells using a photosensitiser which is selectively retained with the endolysosomal membranes. Excitation of the photosensitiser by visible light leads to disruption of the membranes via photooxidative damage thereby releasing the agent into the cytosol. This treatment enables the drugs to reach their intended subcellular target more efficiently and improves their efficacy. In this review we summarise the applications of this technique with the main emphasis placed on cancer chemotherapy.
Highlights
The combined effect of either photosensitiser TPPS2a or AlPcS2a with saporin was recently compared using human vascular endothelial cells (HUVECs) and fibrosarcoma cells.[64]. Both photosensitisers were more efficiently taken up by HUVEC cells and found to be located in endocytic vesicles. These results suggest more attention should be given to vascular endothelial cells during Photochemical internalisation (PCI) treatment given the capacity of both Photodynamic Therapy (PDT) and PCI to act on endothelial cells, which in a physiological environment could be translated into vascular shutdown
PCI is a very versatile technique which has been shown to be effective for delivery of drugs exhibiting diverse physicochemical properties and sizes and may find application for cytosolic delivery in the emerging field of “nanomedicine.” Site-specific light application to the target lesion results in the focal delivery of therapeutic compounds, thereby minimising damage to normal adjacent tissue[8,15] this means that PCI is only suitable for local treatment of cancer
PCI could potentially widen the range of chemotherapy options to include relatively cytotoxic chemotherapy drugs whose dosages could be lowered while maintaining their therapeutic effect
Summary
Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation Alejandra Martinez de Pinillos Bayona, Caroline M. UCL Division of Surgery and Interventional Sciences, University College London, London, United Kingdom
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