title: Efficacy of photochemical internalisation using disulfonated chlorin and porphyrin photosensitisers: An in vitro study in 2D and 3D prostate cancer models.
abstract: This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS2aand TPPS2a) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI). TPPS2aand TPCS2awere shown to be located in discrete cytoplasmic vesicles before light treatment and redistribute into the cytosol upon light excitation. PC3 cells exhibit a higher uptake than MatLyLu cells for both photosensitisers. In the 2D model, PCI resulted in greater cell death than PDT alone in both cell lines. In 3D model, morphological changes were also observed. Saporin-based toxicity was negligible in PC3 cells, but pronounced in MatLyLu cells (IC50 = 18 nM). In conclusion, the study showed that tumour features such as tumour cell growth rate or interaction with drugs determine therapeutic conditions for optimal photochemical treatment in metastatic prostate cancer.
authors.affiliation: Division of Surgery and Interventional Sciences, University College London, London, United Kingdom. Electronic address: a.martinezdepinillos.12@ucl.ac.uk.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martinez de Pinillos Bayona
authors.affiliation: Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Woodhams
authors.affiliation: Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.
authors.forename: Hayley
authors.initials: H
authors.lastname: Pye
authors.affiliation: Division of Surgery and Interventional Sciences, University College London, London, United Kingdom; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
authors.forename: Rifat A
authors.initials: RA
authors.lastname: Hamoudi
authors.affiliation: Division of Surgery and Interventional Sciences, University College London, London, United Kingdom; Department of Urology, University College London Hospital, London, United Kingdom.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Moore
authors.affiliation: Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: MacRobert
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001557:Benzenesulfonates / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D040761:Biomimetic Materials; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020100:Hydrogels; D008297:Male; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D011166:Porphyrins / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001557:Benzenesulfonates; D020100:Hydrogels; D017319:Photosensitizing Agents; D011166:Porphyrins; D054789:Ribosome Inactivating Proteins, Type 1; C000621865:TPPS2a chlorin; C559366:meso-tetraphenyl chlorin disulphonate; C006969:chlorin; D003094:Collagen; D000076985:Saporins
keywords: Photochemical internalisation (PCI); Photodynamic therapy (PDT); Prostate cancer; TPCS(2a); TPPS(2a)