Photochemical internalization

Solute/solvent 1 1 complexes can be formed, of course, in the ground as well as in excited states. Since solutes that show photochemical internal twisting normally possess polar substituent groups, the probability of complex formation is rather high. Thus, studies of the photophysics of internal twisting must be carried out carefully enough to avoid errors due to complex formation. 

Berg K, Selbo PK, Prasmickaite L et al (1999) Photochemical internalization a novel technology for delivery of macromolecules into cytosol. Cancer Res 59 1180-1183... 

Oliveira S, Fretz MM, Hogset A et al (2007) Photochemical internalization enhances silencing of epidermal growth factor receptor through improved endosomal escape of siRNA. Biochim Biophys Acta 1768 1211-1217... 

Photochemical Internalization A New Tool for Gene and Oligonucleotide Delivery... 

Keywords Drug delivery Gene therapy Macromolecule Peptide nucleic acid Photochemical internalization Photodynamic Photosensitizer Protein toxin siRNA... 

Matsumoto, K. et al., Insulin enhances macrophage scavenger receptor-mediated endocytotic uptake of advanced glycation endproducts, J. Biol. Chem. 273,8630-8637,1998). There is some interest in receptor-mediated endocytosis for drug delivery (Selbo, P.K., Hogset, A., Prasmickaite, L., and Berg, K Photochemical internalization a novel dmg delivery system. Tumour Biol. 23, 102-112, 2002). 

Some sensitizers, such as the water-soluble TPPS and AlPcS, localize in lysosomes, which disrupt during PDT [88,89]. The sensitizers are then relocalized in the cells and may even enter the nucleus [89]. Lysosomal damage leads to leakage of the contents of the lysosomes into the cytoplasm. One of the hottest and most promising applications of PDT may turn out to be photochemical internalization the use of PDT to liberate molecules taken up by endosomes and lysosomes (toxins, DNA fragments etc.) into the cytoplasm. Several extremely promising applications of this technique have been proposed and demonstrated [90] since lysosomal disruption in vivo had been demonstrated in 1996 [91]. 

Cell culture experiments [54] showed that large-sized PEI/DNA polyplexes (aggregates of several hundred nm) are more effective but more toxic. The endosomal escape is thought not to be the major bottleneck for such large particles. Small PEI/DNA particles, around 50-100nm, however, have lower efficacy, resulting from an inefficient endosomal release. Photochemical internalization (PCI) is one method to enhance efficiency of the small PEI polyplexes [43,57]. 

Selbo, P.K., Sivam, G., Fodstad, O., Sandvig, K., and Berg, K., In vivo documentation of photochemical internalization, a novel approach to site specihc cancer therapy, Int. J. Cancer, 92, 761, 2001. 

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