Hyaluronic acid conjugates for topical treatment of skin cancer lesions.
Vinu KrishnanKevin PengApoorva SarodeSupriya PrakashZongmin ZhaoSergey K FilippovKristina TodorovaBrittney R SellOmar Lujano-OlazabaShirin BakreAnusha PusuluriDouglas VogusKenneth Y TsaiAnna MandinovaSamir S MitragotriPublished in: Science advances (2021)
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.
Keyphrases
- skin cancer
- wound healing
- hyaluronic acid
- soft tissue
- induced apoptosis
- papillary thyroid
- cancer therapy
- drug delivery
- oxidative stress
- cell cycle arrest
- minimally invasive
- primary care
- emergency department
- squamous cell carcinoma
- cell proliferation
- smoking cessation
- signaling pathway
- anti inflammatory
- childhood cancer
- structural basis
- adverse drug