Polyion complex micelles entrapping cationic dendrimer porphyrin: effective photosensitizer for photodynamic therapy of cancer.
Photosensitizers play a crucial role in the photodynamic therapy (PDT) of cancer. In this study, a third-generation aryl ether dendrimer porphyrin with 32 primary amine groups on the periphery, [NH2CH2CH2NHCO]32DPZn, and pH-sensitive, polyion complex micelles (PIC) composed of the porphyrin dendrimer and PEG-b-poly(aspartic acid), were evaluated as new photosensitizers (PSs) for PDT in the Lewis Lung Carcinoma (LLC) cell line. The preliminary photophysical characteristics of [NH2CH2CH2NHCO]32DPZn and the corresponding micelles were investigated. Electrostatic assembly resulted in a red-shift of the Soret peak of the porphyrin core and the enhanced fluorescence. Compared to the dendrimer porphyrin [NH2CH2CH2NHCO]32DPZn, relatively low cellular uptake of dendrimer porphyrin [NH2CH2CH2NHCO]32DPZn incorporated in the PIC micelle was observed, yet the latter exhibited enhanced photodynamic efficacy on the LLC cell line. Importantly, the use of PIC micelles as a delivery system reduced the dark toxicity of the cationic dendrimer porphyrin, probably due to the biocompatible PEG shell of the micelles.
Zhang
Guo-Dong
GD
Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Japan.
Harada
Atsushi
A
Nishiyama
Nobuhiro
N
Jiang
Dong-Lin
DL
Koyama
Hiroyuki
H
Aida
Takuzo
T
Kataoka
Kazunori
K
D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D004337:Drug Carriers / Q000494:pharmacology*; D005544:Forecasting; D046911:Macromolecular Substances; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008823:Micelles; D036103:Nanotechnology; D009369:Neoplasms / Q000628:therapy*; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D010789:Phototherapy; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers; D011166:Porphyrins / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D046911:Macromolecular Substances; D008665:Metalloporphyrins; D008823:Micelles; D010647:Phenyl Ethers; D017319:Photosensitizing Agents; D011108:Polymers; D011166:Porphyrins; D011506:Proteins; C493635:polyethylene glycol-block-polyaspartic acid; D001224:Aspartic Acid; D011092:Polyethylene Glycols