Targeting-triggered porphysome nanostructure disruption for activatable photodynamic therapy.
Photodynamic therapy (PDT) and photothermal therapy (PTT) possess advantages over the conventional therapies with additional treatment selectivity achieved with local laser irradiation. Comparing to PTT that ablates target tissue via thermal necrosis, PDT induces target cell death via singlet oxygen without damaging the underling connective tissue, thus preserving its biological function. Activatable photosensitizers provide an additional level of treatment selectivity via the disease-associated activation mechanism. In this study, folate-conjugated porphysomes are introduced as targeting-triggered activatable nano-sized beacons for PDT. Porphysomes are reported previously as the most stable and efficient delivery system of porphyrin, but their nanostructure converts the singlet oxygen generation mechanism to thermal ablation mechanism. By folate-receptor-mediated endocytosis, folate-porphysomes are internalized into cells rapidly and resulted in efficient disruption of nanostructures, thus switching back on the photodynamic activity of the densely packed porphyrins for effective PDT. In both in vitro and in vivo studies, folate-porphysomes can achieve folate receptor-selective PDT efficacy, which proves the robustness of targeting-triggered PDT activation of porphysome nanostructure for highly selective tumor ablation. The formulation of porphysomes can be modified with other targeting ligands as activatable photosensitizers for personalized treatment in future.
Ontario Cancer Institute and Techna Institute, University Health Network, 101 College Street, Toronto, Ontario, M5G 1L7, Canada; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 101 College Street, Toronto, Ontario, M5G 1L7, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, 101 College Street, Toronto, Ontario, M5G 1L7, Canada.
Cheng S
CS
Jin
Liyang
L
Cui
Fan
F
Wang
Juan
J
Chen
Gang
G
Zheng
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis; D058973:Folate Receptors, GPI-Anchored / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D007834:Lasers; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D011166:Porphyrins / Q000737:chemistry; D026082:Singlet Oxygen / Q000378:metabolism; D015996:Survival Rate; D014183:Transplantation, Heterologous
D058973:Folate Receptors, GPI-Anchored; D017319:Photosensitizing Agents; D011166:Porphyrins; D026082:Singlet Oxygen; D005492:Folic Acid
folate receptor; nanoparticles; photosensitizer; porphyrin; porphysomes