A transdermal drug delivery cream, which is non‐invasive and painless, containing a liposome‐encapsulated Ru(II) complex (LipoRu) is created for the treatment of skin cancer. This formulation capitalizes on the synergistic antitumor effects of two‐photon excited photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. LipoRu exhibits effective tumor accumulation, efficient cellular uptake, pH‐sensitive and infrared‐accelerated release, and dual localization to the nucleus and mitochondria. The released Ru(II) complexes within cells exert multiple antitumor mechanisms, such as DNA topoisomerase and RNA polymerase inhibition, Type I and II PDT, PTT, DNA photodamage, and apoptosis and ferroptosis induction. The biodistribution and therapeutic efficacy of LipoRu in vivo are systematically compared via three distinct administration routes: intratumoral injection, intravenous injection, and transdermal delivery through topical cream application. The positive therapeutic effects of the LipoRu cream fabricated here in subcutaneous tumor‐bearing mice offer optimistic potential for the painless and non‐invasive treatment of both early‐stage and advanced skin cancers, as well as superficially located solid tumors.

中文翻译：

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抗肿瘤乳膏：含有脂质体包封的钌复合物的透皮水凝胶，用于红外控制的多模式协同治疗


一种无创且无痛的透皮给药乳膏，含有脂质体封装的 Ru（II） 复合物 （LipoRu），用于治疗皮肤癌。该制剂利用了双光子激发光动力疗法 （PDT）、光热疗法 （PTT） 和化疗的协同抗肿瘤作用。LipoRu 表现出有效的肿瘤积累、高效的细胞摄取、pH 敏感和红外加速释放以及细胞核和线粒体的双重定位。细胞内释放的 Ru（II） 复合物发挥多种抗肿瘤机制，如 DNA 拓扑异构酶和 RNA 聚合酶抑制、I 型和 II 型 PDT、PTT、DNA 光损伤以及细胞凋亡和铁死亡诱导。通过三种不同的给药途径系统比较 LipoRu 在体内的生物分布和治疗效果：瘤内注射、静脉注射和通过局部乳膏应用透皮给药。在皮下荷瘤小鼠中制备的 LipoRu 乳膏的积极治疗效果为早期和晚期皮肤癌以及浅表实体瘤的无痛和无创治疗提供了乐观的潜力。