학회 | 한국고분자학회 |
학술대회 | 2004년 가을 (10/08 ~ 10/09, 경북대학교) |
권호 | 29권 2호, p.54 |
발표분야 | 의료용 고분자 부문위원회 |
제목 | Polyion complex micelles encapsulating dendrimer porphyrins for photodynamic therapy |
초록 | Photodynamic Therapy (PDT) involves the administration of a photosensitizer, which preferentially accumulates in target tissues. Subsequent activation by light at a wavelength matching its absorption wavelength leads to the formation of highly reactive singlet oxygen that causes the destruction of target cells by a complex cascade of chemical, biological and physiological reactions. As a revolutionary method in preclinical and clinical applications over the last few decades, numerous attempts have been made to improve the PDT efficacy. Among them, to create an efficient photosensitizer and accumulate it effectively in a tissue is an attractive topic. An efficient photosensitizer should have the properties: (1) high quantum yield, (2) effective absorption, (3) good solubility in aqueous medium, (4) less dark toxicity and high photocytotoxicity, and (5) preferential selectivity to the malignant tissue. We have recently reported on dendrimer porphyrins (DPs) as a potential photosensitizer candidate in PDT because DPs exhibit high solubility in an aqueous medium and have a high quantum yield for singlet oxygen generation. In this study, we have studied a novel polyion complex (PIC) system composed of different generation (1st, 2nd, or 3rd) DP and poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL) in aqueous medium. The electrostatic interaction between the cationic PLL segment and anionic charges on periphery of DPs provided a driving force of complex formation. Static (SLS) and dynamic (DLS) light scattering as well as electronic absorption and emission spectra have been applied in the investigation of the complex properties and photophysical properties of DP and DP in PIC. The properties of these PICs strongly depend on the generation of DP. Particularly, 3rd generation DP incorporated in PIC micelles show a high stability in physiological saline and strong fluorescence compared with other generation DP/PIC systems. This result coincides with the fast oxygen consumption (measured by an oxygen electrode) in 3rd generation DP micelle systems. Therefore, it is possible that 3rd DP micelles can lead to higher singlet oxygen quantum yield and enhance PDT efficacy more effectively than other generation DP micelles. In vitro PDT effect of 3rd DPs and 3rd DP micelles were also evaluated in the Hela cells. The cellular uptake amount of 3rd DP micelles showed more than 6 times higher than that of 3rd DPs. The photocytotoxicity of 3rd DP micelles was remarkably improved compared with that of 3rd DPs alone. Incorporation of DP into the micelles resulted in approximately 130 times increased photocytotoxicity. |
저자 | 장우동1, Yuan Li2, Nobuhiro Nishiyama3, Kazunori Kataoka2 |
소속 | 1JST CREST / Department of Materials Engineering, 2The Univ. of Tokyo, 3Department of Materials Engineering |
키워드 | photodynamic therapy; polyion complex micelle; dendrimer |