Photodynamic Characterization of Amino Acid Conjugated 151-Hydroxypurpurin-7-lactone for Cancer Treatment
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- 作者：Siang Hui Lim ; Mun Li Yam ; May Lynn Lam ; Fadzly Azhar Kamarulzaman ; Norazwana Samat ; Lik Voon Kiew ; Lip Yong Chung ; Hong Boon Lee
- 刊名：Molecular Pharmaceutics
- 出版年：2014
- 出版时间：September 2, 2014
- 年：2014
- 卷：11
- 期：9
- 页码：3164-3173
- 全文大小：474K
- ISSN：1543-8392
文摘
This study aims to improve the photodynamic properties and biological effectiveness of 151-hydroxypurpurin-7-lactone dimethyl ester (G2), a semisynthetic photosensitizer, for the PDT treatment of cancer. The strategy we undertook was by conjugating G2 with aspartic acid and lysine amino acid moieties. The photophysical properties, singlet oxygen generation, distribution coefficiency (Log D in octanol/PBS pH 7.4), and photostability of these analogues and their in vitro bioactivities such as cellular uptake, intracellular localization, and photoinduced cytotoxicity were evaluated. In addition, selected analogues were also investigated for their PDT-induced vasculature occlusion in the chick chorioallantoic membrane model and for their antitumor efficacies in Balb/C mice bearing 4T1 mouse mammary tumor. From the study, conjugation with aspartic acid improved the aqueous solubility of G2 without affecting its photophysical characteristics. G2-Asp showed similar in vitro and in vivo antitumor efficacies compared to the parent compound. Given the hydrophilic nature of G2-Asp, the photosensitizer is a pharmaceutically advantageous candidate as it can be formulated easily for systemic administration and has reduced risk of aggregation in vascular system.