Improved Photodynamic Cancer Treatment by Folate‐Conjugated Polymeric Micelles in a KB Xenografted Animal Model

光敏剂 光毒性 光动力疗法 胶束 共轭体系 叶酸受体 体内 化学 生物物理学 体外 光化学 癌细胞 癌症 有机化学 生物化学 医学 生物 聚合物 内科学 生物技术 水溶液
作者
Wei‐Jhe Syu,Hsiu‐Ping Yu,Chia‐Yen Hsu,Yeasudhasan Christu Rajan,Yuan‐Hung Hsu,Yuan‐Chia Chang,Wen‐Yuan Hsieh,Chau‐Hui Wang,Ping‐Shan Lai
出处
期刊:Small [Wiley]
卷期号:8 (13): 2060-2069 被引量:66
标识
DOI:10.1002/smll.201102695
摘要

Abstract Photodynamic therapy (PDT) is a light‐induced chemical reaction that produces localized tissue damage for the treatment of cancers and various nonmalignant conditions. In the clinic, patients treated with PDT should be kept away from direct sunlight or strong indoor lighting to avoid skin phototoxicity. In a previous study, it was demonstrated that the skin phototoxicity of meta ‐ tetra (hydroxyphenyl)chlorin (m‐THPC), a photosensitizer used in the clinic, can be significantly reduced after micellar encapsulation; however, no improvement in antitumor efficacy was observed. In this work, a folate‐conjugated polymeric m‐THPC delivery system is developed for improving tumor targeting of the photosensitizer, preventing photodamage to the healthy tissue, and increasing the effectiveness of the photosensitizers. The results demonstrate that folate‐conjugated m‐THPC‐loaded micelles with particle sizes around 100 nm are taken up and accumulated by folate receptor‐overexpressed KB cells in vitro and in vivo, and their PDT has no significant adverse effects on the body weight of mice. After an extended delivery time, a single dose of folate‐conjugated m‐THPC‐loaded micelles has higher antitumor effects (tumor growth inhibition = 92%) through inhibition of cell proliferation and reduction of vessel density than free m‐THPC or m‐THPC‐loaded micelles at an equivalent m‐THPC concentration of 0.3 mg kg −1 after irradiation. Furthermore, folate‐conjugated m‐THPC‐loaded micelles at only 0.2 mg kg −1 m‐THPC have a similar antitumor efficacy to m‐THPC or m‐THPC‐loaded micelles with the m‐THPC concentration at 0.3 mg kg −1 , which indicates that the folate conjugation on the micellar photosensitizer apparently reduces the requirement of m‐THPC for PDT. Thus, folate‐conjugated m‐THPC‐loaded micelles with improved selectivity via folate–folate receptor interactions have the potential to reduce, not only the skin photosensitivity, but also the drug dose requirement for clinical PDT.

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