Defeating Melanoma Through a Nano-Enabled Revision of Hypoxic and Immunosuppressive Tumor Microenvironment

Wenzhe Yang,1,2,* Xue Pan,2,* Peng Zhang,2 Xue Yang,1,2 Huashi Guan,1,2 Huan Dou,3 Qian Lu1,2 1Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong Province, People’s Republic of China; 2Marine Traditional Chinese Medicine R&D Laboratory, Marine Biomedical Research Institute of Qingdao, Qingdao, Shandong Province, People’s Republic of China; 3Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Lu, Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, Shandong Province, People’s Republic of China, Tel +86 15850672529, Fax +86 532 8506779, Email lq7080@ouc.edu.cn Huan Dou, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu Province, 210093, People’s Republic of China, Tel +86 13913832488, Fax +86 025 83686441, Email douhuan@nju.edu.cnRationale: Reversing the hypoxic and immunosuppressive tumor microenvironment (TME) is crucial for treating malignant melanoma. Seeking a robust platform for the effective reversion of hypoxic and immunosuppressive TME may be an excellent solution to revolutionizing the current landscape of malignant melanoma treatment. Here, we demonstrated a transdermal and intravenous dual-administration paradigm. A tailor-made Ato/cabo@PEG-TK-PLGA NPs were administrated transdermally to melanoma with the help of a gel spray containing a skin-penetrating material borneol. Nanoparticles encased Ato and cabo were released and thereby reversed the hypoxic and immunosuppressive tumor microenvironment (TME).Methods: Ato/cabo@PEG-TK-PLGA NPs were synthesized through a self-assembly emulsion process, and the transdermal ability was assessed usin