Skin cancer is one of the most common types of cancer in the United States and worldwide. Topical products are effective for treating cancerous skin lesions when surgery is not feasible. However, current topical products induce severe irritation, light-sensitivity, burning, scaling, and inflammation. Using hyaluronic acid (HA), we engineered clinically translatable polymer-drug conjugates of doxorubicin and camptothecin termed, DOxorubicin and Camptothecin Tailored at Optimal Ratios (DOCTOR) for topical treatment of skin cancers. When compared to the clinical standard, Efudex, DOCTOR exhibited high cancer-cell killing specificity with superior safety to healthy skin cells. In vivo studies confirmed its efficacy in treating cancerous lesions without irritation or systemic absorption. When tested on patient-derived primary cells and live-skin explants, DOCTOR killed the cancer with a selectivity as high as 21-fold over healthy skin tissue from the same donor. Collectively, DOCTOR provides a safe and potent option for treating skin cancer in the clinic.

皮肤癌是美国和全世界最常见的癌症类型之一。当手术不可行时，局部产品可有效治疗癌性皮肤病变。然而，目前的外用产品会引起严重的刺激、光敏性、灼痛、脱屑和炎症。使用透明质酸 (HA)，我们设计了临床上可翻译的多柔比星和喜树碱聚合物-药物偶联物，称为以最佳比例定制的多柔比星和喜树碱 (DOCTOR)，用于皮肤癌的局部治疗。与临床标准 Efudex 相比，DOCTOR 表现出较高的癌细胞杀伤特异性，并且对健康皮肤细胞具有更高的安全性。体内研究证实了它在治疗癌性病变方面的功效，没有刺激或全身吸收。在对患者来源的原代细胞和活体皮肤外植体进行测试时，DOCTOR 杀死癌症的选择性比来自同一供体的健康皮肤组织的选择性高 21 倍。总的来说，DOCTOR 为临床治疗皮肤癌提供了一种安全有效的选择。