Preparation of poly(ethylene glycol)-attached dendrimers encapsulating photosensitizers for application to photodynamic therapy.
Photodynamic therapy (PDT) is a noninvasive treatment of some diseases including cancer. We have developed poly(ethylene glycol) (PEG)-attached dendrimers as a drug-carrier candidate. In this study, we prepared nanocapsules of photosensitizers using PEG-attached dendrimers for application to PDT. Two PEG-attached dendrimers derived from poly(amido amine) (PAMAM) and poly(propylene imine) (PPI) dendrimers (PEG-PAMAM and PEG-PPI) were synthesized, and rose bengal (RB) and protoporphyrin IX (PpIX) were used as photosensitizers. Results showed that fewer PpIX molecules were encapsulated by both PEG-attached dendrimers than RB, but the complexes were more stable under physiological conditions. Furthermore, we demonstrated that PEG-PPI held photosensitizers in a more stable manner than PEG-PAMAM because of their inner hydrophobicity. We described the cytotoxicity of the complexes of photosensitizers induced by light irradiation in vitro. The complex of PpIX with PEG-PPI exhibited efficient cytotoxicity, compared with free PpIX. It was suggested that the cytotoxicity was caused by the high level of singlet oxygen production and the efficient delivery to mitochondria. Our results suggest that these PEG-attached dendrimers are a promising vehicle for PDT.
Kojima
Chie
C
Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
Toi
Yoko
Y
Harada
Atsushi
A
Kono
Kenji
K
D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D008027:Light; D053769:Nanocapsules / Q000737:chemistry* / Q000633:toxicity; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D026082:Singlet Oxygen / Q000737:chemistry
D050091:Dendrimers; D004337:Drug Carriers; D053769:Nanocapsules; C522249:PEG-PAMAM; D017319:Photosensitizing Agents; D011073:Polyamines; C522250:polyethylene glycol-poly(propylene imine); D026082:Singlet Oxygen; D011092:Polyethylene Glycols