Open AccessHyaluronic acid conjugates for topical treatment of skin cancer lesions
Author(s) -
Vinu Krishnan,
Kevin Peng,
Apoorva Sarode,
Supriya Prakash,
Zongmin Zhao,
Sergey K. Filippov,
Katerina Todorovа,
Brittney R. Sell,
Omar Lujano-Olazaba,
Shirin Bakre,
Anusha Pusuluri,
Douglas R. Vogus,
Kenneth Y. Tsai,
Anna Mandinova,
Samir Mitragotri
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abe6627
Subject(s) - medicine , hyaluronic acid , skin cancer , camptothecin , irritation , cancer , in vivo , dermatology , doxorubicin , cancer cell , drug , pharmacology , chemotherapy , surgery , immunology , chemistry , biology , microbiology and biotechnology , organic chemistry , anatomy
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.