Targeting-Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy

• Published in: Advanced healthcare materials Vol. 3; no. 8; pp. 1240 - 1249
• Main Authors: Jin, Cheng S., Cui, Liyang, Wang, Fan, Chen, Juan, Zheng, Gang
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.08.2014; Wiley Subscription Services, Inc
• Subjects: Ablation; Animals; Cell Line, Tumor; Cell Survival - drug effects; Disruption; Endocytosis; folate receptor; Folate Receptors, GPI-Anchored - genetics; Folate Receptors, GPI-Anchored - metabolism; Folic Acid - chemistry; Formulations; Humans; Lasers; Mice; Mice, Nude; nanoparticles; Nanostructure; Nanostructures - chemistry; Neoplasms - drug therapy; Neoplasms - mortality; Neoplasms - pathology; Oxygen; Photochemotherapy; Photodynamic therapy; photosensitizer; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - chemistry; Photosensitizing Agents - toxicity; porphyrin; Porphyrins; Porphyrins - chemistry; porphysomes; Singlet oxygen; Singlet Oxygen - metabolism; Survival Rate; Switching; Therapy; Transplantation, Heterologous; folate receptor; nanoparticles; porphyrin; photosensitizer; porphysomes
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.201300651

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. Activatable nano‐sized beacons for photo­dynamic therapy (PDT): Intact porphysome nanoparticles are inactive for PDT. By incorporating targeting ligands (e.g., folate) into porphysome formulation, receptor‐mediated endocytosis facilitates the disruption of the nanostructure inside cells, thus switching back on the photo­dynamic activity of the densely packed porphyrins for effective PDT.