Photodynamic therapy (PDT) has emerged as an attractive therapeutic modality for the targeted destruction of abnormal cells as it involves the specific generation of reactive oxygen species (ROS) in tissue only in the combined presence of a photosensitizer (PS), incident excitation light, and molecular oxygen. A variety of effective PS molecules have been developed but they are often limited by poor water solubility or a lack of cell-type specificity. We have developed a quantum dot-chlorin e6 (QD-Ce6) nanobioconjugate system where the QD (5 nm diameter) serves simultaneously as a hydrophilic scaffold and an efficient Förster resonance energy transfer (FRET) donor to multiple Ce6 PS acceptors arrayed around the central QD. Decoration of the conjugate with a membrane-tethering peptide stably localizes the ensemble conjugate system on the exofacial leaflet of the plasma membrane of mammalian cells. Excitation of Ce6 in a FRET configuration results in membrane-localized ROS generation resulting in lipid peroxidation, increased membrane permeability, and inhibition of cellular proliferation. We present and discuss our results in the context of the further evolution of QD-based PDT systems.

光动力疗法 (PDT) 已成为靶向破坏异常细胞的一种有吸引力的治疗方式，因为它仅在光敏剂 (PS)、入射激发光、和分子氧。已经开发了多种有效的 PS 分子，但它们通常受到水溶性差或缺乏细胞类型特异性的限制。我们开发了一种量子点-二氢卟酚 e6 (QD-Ce6) 纳米生物共轭系统，其中 QD（5 nm 直径）同时用作亲水支架和有效的 Förster 共振能量转移（FRET）供体，用于排列在中心周围的多个 Ce6 PS 受体量子点。用膜束缚肽装饰缀合物将整体缀合物系统稳定地定位在哺乳动物细胞质膜的外表面小叶上。在 FRET 配置中激发 Ce6 导致膜局部 ROS 生成，导致脂质过氧化、膜通透性增加和细胞增殖抑制。我们在基于 QD 的 PDT 系统进一步发展的背景下介绍和讨论我们的结果。