Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules

Synergistic chemotherapy by combined moderate hyperthermia and photochemical internalization

“…MHT alone most probably facilitates enhanced drug efficacy by increasing cellular uptake via endocytosis. Both PCI and MHT have been shown to promote endosomal escape and the release of drug into the cytosol [16,19]. In addition, both drugs used in this study are incorporated into DNA causing damage which often results in cell death unless the damage is repaired.…”

“…PCI, based on the principles of PDT, is a technique that improves the utilization of macromolecules in cancer therapy in a site-specific manner [15][16][17][18]. The concept is based on the use of specially designed photosensitizers, with two sulfonate groups on adjacent phenyl rings such as TPPS2a AlPcS2a and TPCS2a, that localize preferentially in the membranes of endocytic vesicles.…”

Endosomal Escape Pathways for Non-Viral Nucleic Acid Delivery Systems

“…Photosensitizers that are employed in the PCI technology are usually amphiphilic compounds which can bind to and localize in the plasma membrane. After being taken up by the cells through endocytosis, the photosensitizers are confined to the endosomal membranes and remain inactive until triggered by light with specific wavelengths matching their absorption spectra (Selbo, Weyergang et al 2010). Once activated, they induce the formation of highly reactive oxygen species, mainly singlet oxygen, leading to the rupture of endosomes and lysosomes membrane.…”

“…PCI principally targets cellular endocytosis that may affect the distribution of molecules that are taken up by the cells via endosomal pathway. It was later employed as a tool to improve the cellular delivery of a large variety of bioactive macromolecules and nucleic acids including pDNA, siRNA and oligonucleotides (Selbo, Weyergang et al 2010). Examples of photosensitizers that are used in non-viral nucleic acid delivery including disulfonated meso-tetraphenylporphine (TPPS2a) (Prasmickaite, Høgset et al 2000;Kloeckner, Prasmickaite et al 2004;Maurice-Duelli, Ndoye et al 2004;Ndoye, Merlin et al 2004;Ndoye, Dolivet et al 2006;Oliveira, Fretz et al 2007;Boe, Longva et al 2008;Raemdonck, Naeye et al 2009;Bøe, Saebøe-Larssen et al 2010), disulfonated aluminium phthalocyanine (AlPcS2a) (Berg, Prasmickaite et al 2003;Hellum, Høgset et al 2003;Ndoye, Dolivet et al 2006;Yip, Weyergang et al 2007), Zincphthalocyanine (Zn-Pc) dendrimer (Nishiyama, Iriyama et al 2005;Arnida, Nishiyama et al 2006) and 5,10,15-tri(4-acetamidophenyl)-20-mono(4-carboxyl-phenyl)porphyrin (TAMCPP) conjugated to G4 PAMAM dendrimer (Shieh, Peng et al 2008).…”

Emerging Strategies for Controlling Drug Release by Using Visible/Near IR Light

“…Berg et al developed photochemical internalization (PCI), a novel method to release drugs in endocytic vesicles to enhance the therapeutic effects ( Figure 6) [34]. PCI is now a well-established method and has been applied to enhance the delivery various therapeutic molecules [35][36][37]. While PCIuses random oxidation of endo/lysosomal membranes to release the contents from the vesicles, chemically controlled approachescan also release drugs using photodynamic release.…”